Trials · Topics · GI Cancer

GI Cancer clinical trials

278 GI Cancer trials (Medical Oncology and Radiation Oncology) summarized for fellows and board review, newest first within each disease. Each summary covers design, results, toxicity and what changed in practice.

Jump to: Colon - advanced · HCC - advanced · Rectal · Gastric - advanced · Rectal - LARC · Esophageal · Colon - adjuvant · Gastric - perioperative · Liver · Pancreas - advanced · Anal · NET - advanced · Pancreatic · Biliary - advanced · Colon - perioperative · Esophageal - advanced · Gastric · GIST - metastatic · Anal - advanced · Biliary - adjuvant · Pancreas - adjuvant · Pancreas - perioperative · Esophageal - perioperative · GIST - adjuvant · HCC - adjuvant · Biliary · Gastric - adjuvant

Colon - advanced (32)

BREAKWATER (Cohort 3) Ann Oncol 2026
In first-line BRAF V600E-mutant mCRC, encorafenib + cetuximab + FOLFIRI significantly improved ORR and PFS with prolonged OS versus chemotherapy ± bevacizumab...
COMMIT (NRG-GI004/SWOG-S1610) J Clin Oncol 2026
In first-line dMMR/MSI-H metastatic colorectal cancer, adding mFOLFOX6 and bevacizumab to atezolizumab more than halved the risk of progression versus atezolizumab...
SOLARIS (Alliance A021703) JAMA 2026
High-dose vitamin D3 added to first-line chemotherapy plus bevacizumab did not improve PFS, OS or objective response in metastatic colorectal cancer. SOLARIS is an...
BREAKWATER New England Journal of Medicine 2025
Encorafenib + cetuximab + mFOLFOX6 significantly prolonged both PFS and OS in first-line BRAF V600E-mutated mCRC versus standard chemotherapy ± bevacizumab, roughly...
STELLAR-303 Lancet 2025
STELLAR-303 is the first phase III trial to demonstrate an OS benefit with an immunotherapy-based regimen (zanzalintinib-atezolizumab) in relapsed/refractory MSS...
CheckMate 8HW NEJM 2024
Nivolumab + ipilimumab produced a dramatic improvement in first-line PFS vs chemotherapy in dMMR/MSI-H mCRC (HR 0.21, P<.001), with 72% progression-free at 24 months...
DESTINY-CRC02 Lancet Oncol 2024
T-DXd 5.4 mg/kg achieved ORR of 37.8% in HER2+ mCRC including RAS-mutant and anti-HER2-pretreated patients - with a more favorable safety profile than 6.4 mg/kg. The...
AIO KRK0116 trial JCO 2023
FOLFOXIRI + cetuximab did not achieve a higher ORR than FOLFOXIRI + bevacizumab in BRAF V600E-mutant mCRC; bevacizumab-based chemotherapy remains the preferred...
CODEBREAK 100 trial NEJM 2023
Sotorasib plus panitumumab significantly improved PFS versus standard care in chemorefractory KRAS G12C-mutated metastatic colorectal cancer, with the 960 mg dose...
FRESCO trial Fruquintinib vs pbo Lancet 2023
Fruquintinib significantly improved OS and PFS in heavily pretreated refractory mCRC with manageable VEGFR-class toxicity, establishing a new oral late-line option.
KEYNOTE-177 NEJM 2020
First-line pembrolizumab significantly improved PFS versus chemotherapy with a favorable safety profile in patients with MSI-H/dMMR metastatic colorectal cancer...
MOUNTAINEER Lancet Oncol 2023
Tucatinib + trastuzumab achieved an ORR of 38.1% with mPFS 8.2 months and mOS 24.1 months in heavily pretreated HER2+ RAS wild-type mCRC - the first FDA-approved...
PARADIGM trial JAMA 2023
Adding panitumumab rather than bevacizumab to first-line mFOLFOX6 significantly improved overall survival in RAS wild-type mCRC, with benefit most evident in...
SUNLIGHT NEJM 2023
Adding bevacizumab to TAS-102 produced a clinically meaningful improvement in OS (mOS 10.6 vs 7.5 months, HR 0.61) and PFS (mPFS 5.6 vs 2.4 months, HR 0.44) in...
KRYSTAL-1 (CRC) NEJM 2022
Adagrasib monotherapy produced an ORR of 19% in KRAS G12C mCRC - modest but the first prospective signal of activity for a KRAS inhibitor in CRC. The adagrasib +...
TRIPLETE trial JCO 2022
Intensifying the chemotherapy backbone to FOLFOXIRI added to panitumumab did not improve ORR over FOLFOX + panitumumab in RAS/BRAF wild-type mCRC, while increasing...
KEYNOTE-164 JCO 2020
Pembrolizumab produced clinically meaningful and durable responses in patients with previously treated MSI-H/dMMR mCRC, with ORR ~33% across both cohorts and median...
TRIBE 2 trial Lancet Oncol 2020
Upfront FOLFOXIRI + bevacizumab with reintroduction at progression improved PFS2 versus sequential doublets with bevacizumab and is a preferred strategy for eligible...
BEACON CRC NEJM 2019
The encorafenib + binimetinib + cetuximab triplet produced a landmark improvement in OS (HR 0.52) and ORR (26% vs 2%) vs irinotecan-based control in BRAF V600E mCRC...
CheckMate 142 Lancet Oncol 2017
Nivolumab + ipilimumab produced an ORR of 55% in heavily pretreated dMMR/MSI-H mCRC - a landmark result where chemotherapy response rates are typically <10%. Disease...
CALGB80405 trial JAMA 2017
In KRAS wild-type advanced colorectal cancer, first-line cetuximab and bevacizumab combined with chemotherapy produced no significant difference in overall survival...
AIO 0207 Lancet Oncol 2015
Bevacizumab alone maintenance was non-inferior to 5-FU/LV + bevacizumab for TFS, with substantially lower toxicity and better quality of life. Both maintenance arms...
RECOURSE NEJM 2015
TAS-102 produced a statistically significant OS benefit vs placebo in heavily pretreated mCRC (mOS 7.1 vs 5.3 months, HR 0.68, P<.001), with a manageable...
CAIRO3 Lancet 2015
Maintenance capecitabine + bevacizumab after CAPOX-B induction significantly improved PFS2 (primary endpoint, HR 0.67) and first PFS from randomization (HR 0.44) vs...
FIRE Trial (Final Analysis) Br J Cancer 2021
Although the primary ORR endpoint was not met, FOLFIRI plus cetuximab significantly improved overall survival over FOLFIRI plus bevacizumab in KRAS wild-type mCRC...
PRIME trial Ann Oncol 2014
Panitumumab plus FOLFOX4 significantly improved PFS and OS versus FOLFOX4 alone in RAS wild-type mCRC, while harming outcomes in RAS-mutant patients, confirming...
TRIBE NEJM 2014
FOLFOXIRI + bevacizumab significantly improved PFS (12.1 vs 9.7 months, HR 0.75) and ORR (65% vs 53%) vs FOLFIRI + bevacizumab in first-line mCRC. A trend toward...
CORRECT Lancet 2013
Regorafenib produced a statistically significant OS benefit vs placebo in heavily pretreated mCRC (mOS 6.4 vs 5.0 months, HR 0.77, P=.0052), providing...
CRYSTAL trial NEJM 2009
Adding cetuximab to first-line FOLFIRI improved PFS and response rate in metastatic colorectal cancer, with benefit confined to KRAS wild-type tumors, validating KRAS...
FOLFIRI PLUS Bev in mCRC NEJM 2004
Adding bevacizumab to IFL chemotherapy significantly improved overall survival, progression-free survival, and response rate in metastatic colorectal cancer...
FOLFIRI vs 5FU in metastatic CRC 2000
FOLFIRI improved response rate, time to progression, and overall survival versus 5-FU/leucovorin as first-line therapy for metastatic colorectal cancer, establishing...
FOLFOX vs 5-FU in metastatic CRC JCO 2000
Adding oxaliplatin to infusional 5-FU/leucovorin (FOLFOX4) significantly improved PFS and response rate over LV5FU2 in metastatic colorectal cancer, though the...

HCC - advanced (25)

EMERALD-3 trial Lancet Oncol 2026
STRIDE plus lenvatinib plus TACE significantly improved PFS versus TACE alone (13.0 vs 9.8 mo, HR 0.70) in embolisation-eligible unresectable HCC; STRIDE plus TACE...
TALENTOP trial Lancet 2026
In advanced HCC with macrovascular invasion responding to atezolizumab+bevacizumab, adding conversion liver resection prolonged time to treatment failure vs continued...
TORCH JAMA Oncol 2026
Adding selective thermal ablation after TACE more than doubled median PFS (17.7 vs 7.3 months) and halved the risk of death (HR 0.50) versus TACE alone in...
CheckMate 9DW Lancet 2025
Nivolumab plus ipilimumab significantly improved OS versus lenvatinib or sorafenib as first-line therapy for unresectable HCC, with a median OS benefit of 3.1 months...
EMERALD-1 Lancet 2025
TACE plus durvalumab and bevacizumab significantly improved PFS versus TACE alone in embolization-eligible unresectable HCC, the first ICI-based regimen in a global...
LEAP-012 Lancet 2025
TACE plus lenvatinib and pembrolizumab significantly improved PFS versus TACE plus placebo in unresectable non-metastatic HCC. The OS endpoint was not met at the...
CARES 310 trial Lancet 2023
Camrelizumab plus rivoceranib significantly improved PFS and OS versus sorafenib, supporting it as a new first-line option for unresectable HCC.
LEAP-002 Lancet Oncol 2023
Adding pembrolizumab to lenvatinib did not statistically improve OS or PFS compared with lenvatinib alone as first-line therapy for advanced HCC. Despite promising...
CheckMate 459, Nivo vs Sorafenib in 1L HCC Lancet Oncol 2022
First-line nivolumab did not significantly improve OS versus sorafenib. However, given comparable clinical activity and a favorable safety profile, nivolumab may be...
COSMIC-312 trial, cabo+atezo vs sora Lancet Onc 2022
Cabozantinib plus atezolizumab significantly improved PFS over sorafenib in untreated advanced HCC, but did not improve overall survival, so the combination did not...
HIMALAYA Trial, Tremelimumab plus Durvalumab in Unresectable HCC NEJM Evid 2022
The STRIDE regimen (single priming dose of tremelimumab plus regular-interval durvalumab) significantly improved OS versus sorafenib, and durvalumab monotherapy was...
LAUNCH trial LEN-TACE vs Len alone in adv. HCC 2022
Adding on-demand TACE to lenvatinib significantly improved OS, PFS, and ORR, supporting LEN-TACE as a potential first-line option for advanced HCC.
RATIONALE 302 JCO 2022
Second-line tislelizumab significantly prolonged overall survival versus chemotherapy in advanced/metastatic ESCC, with a more favorable safety profile.
RESCUE Trial Camrelizumab + apatinib Clin Cancer Res 2021
Camrelizumab plus apatinib produced a high objective response rate, durable responses, and prolonged survival with a manageable safety profile in advanced HCC...
Checkmate 040 - Update JAMA Oncol 2020
Nivolumab plus ipilimumab produced durable responses with a manageable safety profile in sorafenib-treated advanced hepatocellular carcinoma, with Arm A showing the...
IMbrave 150, atezo/bev vs sora NEJM 2020
Atezolizumab plus bevacizumab improved OS and PFS versus sorafenib in unresectable hepatocellular carcinoma, establishing a new first-line standard.
KEYNOTE-240 JCO 2020
Pembrolizumab did not meet prespecified statistical significance for either OS or PFS in previously treated HCC. However, numerically meaningful trends were observed...
REACH-2 Lancet Oncol 2019
Ramucirumab significantly improved OS in patients with HCC and AFP ≥400 ng/mL after sorafenib, establishing a biomarker-selected standard for second-line HCC...
Celestial Trial, cabo vs pbo NEJM 2018
Cabozantinib improved OS and PFS versus placebo in previously treated advanced hepatocellular carcinoma.
Keynote 224 2018
Pembrolizumab produced durable objective responses and was well tolerated in advanced hepatocellular carcinoma previously treated with sorafenib.
Len vs Sora trial Lancet 2018
Lenvatinib was non-inferior to sorafenib for overall survival in untreated advanced hepatocellular carcinoma, with superior PFS and response rate.
SHARP trial, Sora vs pbo NEJM 2008
Sorafenib improved median overall survival and time to radiologic progression versus placebo in advanced hepatocellular carcinoma, the first systemic therapy to do so.
Checkmate 040 Lancet 2017
Nivolumab produced durable objective responses with a manageable safety profile across etiologies in advanced hepatocellular carcinoma.
Resorce Trial Lancet 2016
Regorafenib improved overall survival versus placebo in hepatocellular carcinoma progressing on sorafenib, the first agent to show benefit in the second-line setting.
Asia-Pacific sorafenib Lancet Oncol 2009
Sorafenib demonstrated a significant survival benefit versus placebo in Asian HCC patients, confirming efficacy in a population predominantly with HBV-related disease...

Rectal (20)

STAR-TREC trial Lancet Oncol 2026
At 12 months, long-course chemoradiotherapy achieved substantially higher TME-free survival than short-course radiotherapy for organ preservation in...
PREOPANC JCO 2020
Preoperative gemcitabine-based CRT significantly improved OS (HR 0.78, P=.047) and dramatically improved R0 resection rates (71% vs 40%) compared to upfront surgery...
CARTS Study JAMA Surg 2019
Preoperative CRT followed by TEM achieves organ preservation in 72% of T2 and 52% of T3 rectal cancers at 1 year. However, significant salvage surgery rates...
MSKCC Watch and Wait Retrospective JAMA Oncol 2019
Watch-and-wait achieves comparable 3-year OS (95.6% vs 93.2%) to radical resection despite 21.4% local regrowth rate. Near-universal salvageability (96%) of regrowths...
International Watch and Wait Database (IWWD) Lancet 2018
In rectal cancer with cCR after preoperative CRT, watch-and-wait achieves organ preservation in ~75% at 2 yr and 5-yr OS ~85%. Local regrowth (25.2%, most within 2...
MRI Response-Adapted CRT (Markovina) Int J Radiat Oncol Biol Phys 2017
Early MRI response at 3 wk can identify non-responders; escalation to 60 Gy with IMRT is feasible with manageable toxicity and yields pCR (33%) similar to early...
Stockholm III Lancet Oncol 2017
Short-course RT with a delayed interval to surgery (4-8 weeks) achieves significantly fewer postoperative complications than SCRT with immediate surgery and is...
GRECCAR-6 J Clin Oncol 2016
A longer interval (11 vs 7 weeks) after preoperative CRT did not improve pCR and was associated with significantly more operative morbidity and worse mesorectal...
Polish Rectal Cancer Trial Ann Oncol 2016
In fixed/locally advanced rectal cancer, SCRT with immediate surgery and LCCRT with delayed surgery achieved equivalent R0 resection, sphincter preservation, local...
ACOSOG Z6041 Lancet Oncol 2015
Intensified neoadjuvant CRT (capecitabine + oxaliplatin + 54 Gy) achieves a pCR rate of 44.2% in T2N0 distal rectal cancer. The composite endpoint was achieved in...
MSKCC Sequential Neoadjuvant FOLFOX Lancet Oncol 2015
Sequential induction FOLFOX before standard CRT produces a dose-response increase in pCR rates (18% to 38%). Six cycles of induction FOLFOX before CRT achieves ~38%...
ACCORD 12/PRODIGE 2 JCO 2012
Adding oxaliplatin to capecitabine-based preoperative CRT did not significantly improve pCR (19.2% vs 13.9%, P=.09) and substantially increased toxicity. Neither the...
German Rectal Cancer Trial J Clin Oncol 2012
Preoperative CRT significantly reduced local recurrence (7.1% vs 10.1%) and toxicity compared to postoperative CRT without a survival difference at 11 years. Higher...
Ngan Short-Course vs Long-Course CRT J Clin Oncol 2012
Short-course RT was non-inferior to long-course CRT for local recurrence (7.5% vs 4.4%) and OS at 3 years. LCCRT achieves substantially higher pCR rates (15% vs...
Dutch CKVO 95-04 (TME Trial) Lancet Oncol 2011
Preoperative short-course RT significantly halved 12-year local recurrence (5% vs 11%) in the context of TME surgery, but provided no OS or cancer-specific survival...
RTOG Anal/Rectal Contouring Atlas Int J Radiat Oncol Biol Phys 2009
The RTOG consensus atlas provides standardized CTV definitions for IMRT planning of anal and rectal cancer, enabling consistent target delineation across institutions...
EORTC 22921 N Engl J Med 2006
Preoperative CRT significantly improved pathologic complete response rates and local control compared to RT alone, but did not improve OS. Adjuvant chemotherapy after...
Swedish Rectal Cancer Trial JCO 2005
Preoperative short-course radiotherapy (25 Gy/5 fx) significantly reduced 13-year local recurrence (9% vs 26%) and improved OS (38% vs 30%) compared to surgery alone...
RTOG 89-02 Int J Radiat Oncol Biol Phys 2000
Preoperative CRT followed by local excision achieves 100% sphincter preservation. T1 lesions fare well (4% local recurrence at 5 yr). T2 lesions have a substantially...
CALGB 8984 1999
Preoperative CRT followed by local excision (sphincter-sparing) achieves 100% sphincter preservation in T1-T2 low rectal cancer. pCR rates of ~40-44% are achievable....

Gastric - advanced (19)

DRAGON-01 trial JAMA Oncol 2026
Adding intraperitoneal paclitaxel to intravenous paclitaxel plus S-1 significantly prolonged overall survival (median 19.4 vs 13.9mo) and PFS in treatment-naive...
HERIZON-GEA-01 NEJM 2026
In 1L HER2+ advanced gastroesophageal adenocarcinoma, zanidatamab + chemotherapy (with or without tislelizumab) significantly prolonged PFS vs trastuzumab +...
HERIZON-GEA-01 (Phase Ib/II) Clinical Cancer Research 2026
Zanidatamab plus tislelizumab and CAPOX showed clinically meaningful antitumor activity (75.8% cORR) and a manageable safety profile as first-line therapy for HER2+...
Paclitaxel oral solution vs injection, 2L gastric cancer ESMO Open 2026
A paclitaxel oral solution was noninferior to IV paclitaxel for PFS and unexpectedly produced a statistically significant OS advantage (9.13 vs 6.54 months, HR 0.770)...
PERISCOPE II Lancet Oncol 2026
Gastrectomy with cytoreductive surgery and HIPEC provided no overall survival benefit over systemic therapy alone (HR 1.10; P=.70) in gastric cancer with limited...
RELIGHT trial JCO 2026
Adding retlirafusp alfa to first-line CAPOX significantly improved OS and PFS over chemotherapy alone in HER2-negative advanced gastric/GEJ adenocarcinoma, with the...
DESTINY-Gastric02 Lancet Oncol 2023
T-DXd demonstrated clinically meaningful activity (ORR 38-42%) in Western HER2-positive gastric/GEJ cancer after prior trastuzumab, consistent with DESTINY-Gastric01...
GLOW Nat Med 2023
Zolbetuximab + CAPOX significantly improved both PFS and OS vs placebo + CAPOX in CLDN18.2-positive, HER2-negative gastric/GEJ adenocarcinoma (mOS 14.39 vs 12.16 mo...
KEYNOTE-859 Lancet Oncol 2023
Pembrolizumab + chemotherapy significantly improved OS across all PD-L1 subgroups in previously untreated HER2-negative gastric/GEJ adenocarcinoma, with the greatest...
SPOTLIGHT Lancet 2023
Zolbetuximab + mFOLFOX6 significantly improved both PFS and OS vs placebo + mFOLFOX6 in CLDN18.2-positive, HER2-negative gastric/GEJ adenocarcinoma (mOS 18.23 vs...
Checkmate 649 trial 2021
First-line nivolumab plus chemotherapy improved OS and PFS versus chemotherapy alone in advanced gastric/GEJ/esophageal adenocarcinoma, with greatest benefit in PD-L1...
FIGHT Lancet Oncol 2022
Adding bemarituzumab to mFOLFOX6 in first-line FGFR2b-positive gastric/GEJ cancer improved OS and showed a strong PFS trend, with benefit enriched in tumors with high...
JAVELIN Gastric 100 JCO 2021
Switch maintenance with avelumab did not improve OS vs continued chemotherapy in HER2-negative advanced gastric/GEJ cancer, in either the overall population or the...
KEYNOTE-811 trial Nature 2021
Adding pembrolizumab to trastuzumab and chemotherapy in advanced HER2-positive gastric/GEJ adenocarcinoma markedly increased ORR and CR at interim; final analysis...
DESTINY-Gastric01 NEJM 2020
Trastuzumab deruxtecan significantly improved objective response and overall survival versus chemotherapy in heavily pretreated HER2-positive gastric/GEJ...
TAGS Lancet Oncol 2018
Trifluridine/tipiracil significantly improved OS vs placebo in heavily pretreated metastatic gastric cancer (mOS 5.7 vs 3.6 mo, HR 0.69), establishing TAS-102 as a...
RAINBOW 2014
Ramucirumab plus paclitaxel significantly prolonged overall and progression-free survival versus paclitaxel alone in previously treated advanced gastric/GEJ...
REGARD trial Lancet 2014
In patients with advanced gastric or GEJ adenocarcinoma progressing after first-line therapy, ramucirumab monotherapy significantly improved overall survival with a...
ToGA Lancet 2010
Trastuzumab plus chemotherapy significantly improved OS, PFS, and ORR in HER2-positive advanced gastric/GEJ cancer, with greatest benefit in IHC 3+ or IHC 2+/FISH+...

Rectal - LARC (18)

ARISTOTLE Lancet Oncol 2026
Adding weekly irinotecan to capecitabine-based preoperative chemoradiotherapy did not improve disease-free survival in MRI-defined high-risk locally advanced rectal...
TNTCRT trial J Clin Oncol 2026
Compared with conventional neoadjuvant chemoradiotherapy plus adjuvant chemotherapy, doublet long-course TNT (oxaliplatin-containing chemotherapy delivered...
PROSPECT trial NEJM 2023
Neoadjuvant FOLFOX with selective chemoradiotherapy was noninferior to standard preoperative chemoradiotherapy for DFS in patients with locally advanced rectal cancer...
Neadjuvant Dostarlimab in dMMR LARC 2022
Mismatch repair-deficient locally advanced rectal cancer is highly sensitive to single-agent PD-1 blockade with dostarlimab, with all patients achieving clinical...
STELLAR JCO 2022
SCRT followed by sequential CAPOX (a TNT approach) was non-inferior to long-course CRT for 3-year DFS in LARC (HR 0.883). SCRT+CAPOX produced significantly higher pCR...
OPRA trial, TNT vs hx controls. JCO 2022
Total neoadjuvant therapy achieved disease-free survival comparable to historical chemoradiotherapy-surgery-adjuvant controls while allowing roughly half of patients...
CAO/ARO/AIO-12 JCO 2019
Consolidation TNT (CRT → chemotherapy) produced significantly higher pCR than induction TNT (25% vs 17%, P=.046) with numerically higher rates of organ preservation...
CRT+MFOLFOX Lancet Oncol 2015
Adding mFOLFOX6 between chemoradiation and TME significantly increased pathologic complete response in a cycle-dependent manner, supporting consolidation chemotherapy...
POLISH II Study Ann Oncol 2016
There was no difference in local efficacy between short-course RT with consolidation chemotherapy and long-course chemoradiotherapy in cT4 or fixed cT3 rectal cancer....
CAO/ARO/AIO-04 Lancet Oncol 2015
Adding oxaliplatin to neoadjuvant CRT for LARC significantly improved pCR (17% vs 13%, P=.038) and 3-year DFS (HR 0.79, P=.030), though at the cost of increased acute...
Rektum-III trial, cape vs 5FU 2012
Capecitabine is non-inferior (and possibly superior) to fluorouracil in neoadjuvant or adjuvant chemoradiotherapy for locally advanced rectal cancer, supporting oral...
TROG 01.04 JCO 2012
SCRT with delayed surgery produced a 3-year local recurrence rate of 7.5% vs 4.4% with LCRT - an absolute difference of 3.1% that did not reach statistical...
TNT trial JCO 2010
Total neoadjuvant treatment did not improve pCR but achieved markedly better chemotherapy compliance and lower toxicity than postoperative adjuvant CAPOX, providing...
NSABP R-04 trial JCO 2014
Adding oxaliplatin to neoadjuvant fluoropyrimidine chemoradiation did not improve pCR, sphincter preservation, or downstaging but significantly increased toxicity....
Preop vs postop chemo 2004
Preoperative chemoradiotherapy reduced local recurrence, lowered acute and long-term toxicity, and improved sphincter preservation compared with postoperative...
RT before TME trial NEJM 2001
Short-course preoperative radiotherapy reduced 2-year local recurrence in resectable rectal cancer treated with standardized TME, without improving overall survival.
NSABP R-01, first adj chemo in LARC 1988
This historical trial demonstrated a disease-free and overall survival benefit of postoperative chemotherapy in resectable rectal cancer, with greater benefit...
TME trial 1986
Foundational study that introduced total mesorectal excision, demonstrating that meticulous sharp dissection of the mesorectal plane dramatically reduces local...

Esophageal (14)

MDACC Phase II Proton vs IMRT Esophageal J Clin Oncol 2020
Proton beam therapy significantly reduced the total toxicity burden during and after neoadjuvant CRT for esophageal cancer compared to IMRT, without compromising pCR...
Proton vs IMRT Esophageal Cancer JAMA Oncol 2020
Proton CRT for esophageal cancer significantly reduces severe early post-treatment toxicity and hospitalizations compared to photon IMRT, with equivalent pathologic...
CALGB 80803 (PET-Directed CRT) J Clin Oncol 2018
PET-directed adaptive chemotherapy for esophageal adenocarcinoma is feasible. The pCR rates with both FOLFOX-based and carboplatin/paclitaxel-based CRT were modest...
NEOCRTEC5010 J Clin Oncol 2018
Neoadjuvant chemoradiotherapy followed by surgery significantly improved 3-year and 5-year overall survival compared to surgery alone in thoracic esophageal SCC, with...
CROSS (Long-Term Results) Lancet Oncol 2015
Neoadjuvant chemoradiotherapy with carboplatin/paclitaxel and 41.4 Gy followed by surgery significantly improves OS in resectable locally advanced esophageal cancer...
Wu Esophageal IMRT Contouring Guidelines Int J Radiat Oncol Biol Phys 2015
Standardized contouring guidelines using soft-tissue windows reduce inter-observer variability in esophageal cancer RT planning. CTV margins of 3 cm proximal/distal...
PRODIGE5/ACCORD17 Lancet Oncol 2014
FOLFOX achieved similar PFS and OS to cisplatin/5-FU as concurrent CRT for esophageal cancer, with a more favorable hematologic toxicity profile. Formal...
Lin 3D-CRT vs IMRT Esophageal Cancer Int J Radiat Oncol Biol Phys 2012
IMRT for esophageal cancer significantly reduces severe cardiac and pulmonary toxicities compared to 3D-CRT while maintaining equivalent oncologic outcomes. IMRT...
POET Trial J Clin Oncol 2009
Adding preoperative CRT to preoperative chemotherapy for adenocarcinoma of the EGJ significantly increased pCR rates (15.6% vs 2%) and lymph node clearance. The...
CALGB 9781 J Clin Oncol 2008
Trimodality therapy (neoadjuvant CRT followed by esophagectomy) showed significantly improved 5-year OS (39% vs 16%) compared to definitive CRT alone. However, the...
FFCD 9102 J Clin Oncol 2007
In patients with locally advanced thoracic esophageal cancer (predominantly SCC) who respond to initial chemoradiotherapy, continuation of definitive CRT provides...
German Trial (Stahl): SCC, Surgery vs Definitive CRT J Clin Oncol 2005
Adding surgery to chemoradiotherapy improved local tumor control in locally advanced esophageal SCC but did not improve overall survival, compared to definitive...
INT 0123 / RTOG 94-05 (Dose Escalation) J Clin Oncol 2002
Escalating concurrent CRT from 50.4 Gy to 64.8 Gy did not improve local/regional control or overall survival in esophageal cancer. There was a higher number of...
RTOG 8501 (CRT vs RT Alone) JAMA 1999
Combined chemoradiotherapy (cisplatin/5-FU + 50 Gy) significantly prolongs survival in esophageal cancer compared to radiation alone (64 Gy), with 26% 5-year...

Colon - adjuvant (13)

ALTAIR trial Nat Med 2026
In ctDNA-positive, radiologically occult resected CRC, 6 months of post-adjuvant FTD/TPI did not significantly improve DFS versus placebo. ctDNA reliably identified a...
CIRCULATE (AIO/ABCSG) trial Ann Oncol 2026
ITT primary endpoint not met, likely from loss of power after premature closure (only 26 ctDNA+ patients assigned to chemotherapy). ctDNA positivity was strongly...
FIND J Clin Oncol 2026
ctDNA methylation-guided dynamic surveillance did not change how often patients recurred (18.0% vs 18.6%), but doubled the proportion of recurrences amenable to...
NICHE-2 NEJM 2024
Short-course neoadjuvant nivolumab + ipilimumab produced major pathological response in 95% and pCR in 68% of dMMR colon cancer patients, without compromising...
IDEA Collaboration NEJM 2018
Three months of CAPOX is non-inferior to 6 months in stage III colon cancer across risk strata, while 3 months of FOLFOX is not clearly non-inferior in high-risk...
SCOT Lancet Oncol 2018
Three months of adjuvant oxaliplatin-based chemotherapy was non-inferior to 6 months for DFS and OS in stage III CRC, with substantially less peripheral neuropathy....
TOSCA JCO 2018
TOSCA alone failed to definitively prove non-inferiority of 3 vs 6 months FOLFOX4 in stage III colon cancer - the confidence interval extended above the pre-specified...
PETACC-8 Lancet Oncol 2014
Adding cetuximab to adjuvant FOLFOX4 did not improve DFS in KRAS WT or all-RAS WT stage III colon cancer, with a trend toward worse outcomes in KRAS mutant patients....
AVANT Lancet Oncol 2012
Adding bevacizumab to FOLFOX4 or XELOX in stage III adjuvant colon cancer did not improve DFS and showed a non-significant trend toward worse DFS and OS in the...
N0147 JAMA 2012
Adding cetuximab to adjuvant mFOLFOX6 did not improve DFS in KRAS WT stage III colon cancer and was associated with substantially more toxicity. The KRAS mutant...
NSABP C-07 JCO 2011
FLOX significantly improved DFS versus weekly FULV in adjuvant colon cancer, confirming the benefit of oxaliplatin addition first demonstrated in MOSAIC. The OS...
NSABP C-08 NEJM 2011
Adding bevacizumab to adjuvant mFOLFOX6 did not significantly improve DFS in resected stage II/III colon cancer. The DFS curves separated during bevacizumab...
QUASAR Lancet 2007
Adjuvant fluorouracil-based chemotherapy significantly reduced recurrence and improved survival in patients with resected stage II (predominantly) and stage III...

Gastric - perioperative (12)

ASTRUM-006 trial Lancet 2026
Perioperative serplulimab + SOX with a chemotherapy-sparing serplulimab-monotherapy adjuvant phase significantly improved EFS vs perioperative chemotherapy in...
MATTERHORN trial Lancet 2026
Perioperative durvalumab + FLOT significantly improved overall survival (HR 0.78) over FLOT alone, confirming the earlier EFS and pCR benefit. MATTERHORN establishes...
Mountain-02 trial Cancer Cell 2026
Adding perioperative tislelizumab to chemotherapy significantly improved mPR only in tsMHC-II-positive locally advanced gastric/GEJ cancer. tsMHC-II, assessable by...
NeoART ESMO Gastrointestinal Oncology 2026
The NeoART platform trial addresses an unmet need in HER2+ resectable EGA by evaluating the HER2-targeted ADC T-DXd in the neoadjuvant setting, testing whether its...
MATTERHORN NEJM 2025
Perioperative durvalumab + FLOT followed by durvalumab maintenance significantly improved EFS and OS compared to FLOT alone in resectable gastric/GEJ adenocarcinoma...
ATTRACTION-5 Lancet Gastroenterol Hepatol 2024
Adjuvant nivolumab + chemotherapy did not improve relapse-free survival vs placebo + chemotherapy in stage III gastric/GEJ cancer after D2 gastrectomy (HR 0.90...
KEYNOTE-585 Lancet Oncol 2024
Perioperative pembrolizumab + cisplatin-based chemotherapy significantly improved pCR rates but failed to achieve its co-primary endpoints of EFS or OS benefit in...
ARTIST-2 Ann Oncol 2021
SOX for 6 months significantly improved 3-yr DFS vs S-1 monotherapy for 1 year in node-positive gastric cancer after D2 gastrectomy (67.2% vs 53.6%). Adding adjuvant...
FLOT4 Lancet 2019
Perioperative FLOT improved OS (50 vs 35 months, HR 0.77) and significantly increased pCR rates compared to ECF/ECX in resectable gastric and GEJ adenocarcinoma...
ACTS-GC NEJM 2007
One year of adjuvant S-1 significantly improved OS and DFS in Japanese patients with stage II/III gastric cancer after D2 gastrectomy (5-yr OS 71.7% vs 61.1%, HR...
MAGIC Trial N Engl J Med 2006
Perioperative ECF chemotherapy significantly improved OS (HR 0.75) and PFS compared to surgery alone in resectable gastric and lower esophageal/junction...
MacDonald study - INT0116 (SWOG 9008) NEJM 2001
Postoperative chemoradiation improved overall and relapse-free survival versus surgery alone in resected gastric/GEJ adenocarcinoma, establishing adjuvant...

Liver (12)

TACE+SBRT for HCC (Kubo) Hepatol Res 2018
TACE followed by SBRT is safe and achieves effective local control for HCC not amenable to surgery or RFA, contributing additional institutional evidence supporting...
TACE+SBRT vs Sorafenib for HCC with PVTT (Yoon) JAMA Oncol 2018
TACE + SBRT significantly improved TTP (31.0 vs 11.7 weeks) and OS (55 vs 43 weeks) vs sorafenib in HCC with portal vein tumor thrombosis, with superior tumor...
SBRT as Bridge to Transplant for HCC (Sapisochin) J Hepatol 2017
SBRT achieves equivalent dropout rates from the transplant waiting list and equivalent post-transplant survival compared to TACE and RFA in HCC patients awaiting...
Hypofractionated Proton RT for HCC/iCCA (Hong) J Clin Oncol 2016
Hypofractionated proton beam therapy achieved excellent 2-year local control rates (95% HCC, 94% iCCA) with acceptable toxicity, demonstrating the feasibility and...
Phase II TACE+SBRT for HCC (Takeda) Cancer 2016
Sequential TACE + SBRT (35-40 Gy/5 fx) achieved 91% 3-year local control and 70% 3-year OS in unresectable HCC, with acceptable toxicity, confirming this combination...
Proton vs Photon HCC/ICC JCO 2016
Hypofractionated proton therapy achieves superior 2-year local control and better liver function preservation compared to photon 3D-CRT/IMRT for HCC and ICC. These...
SBRT vs RFA for HCC (Wahl) J Clin Oncol 2016
SBRT and RFA achieved similar overall survival and local control for HCC meeting Milan criteria, but SBRT was associated with fewer local-first treatment failures...
Ablative RT Dose Response for IHCC (Tao) J Clin Oncol 2015
Higher ablative doses of RT (BED >80.5 Gy) significantly improved both local control (78% vs 45%) and overall survival (3-year OS 73% vs 38%) for inoperable IHCC...
Phase I/II SBRT for HCC (Bujold) J Clin Oncol 2013
Six-fraction SBRT achieved 87% 1-year local control in locally advanced HCC with TVT and prior treatment failure, with a median OS of 17 months. These results...
Phase II SBRT After TACE for HCC (Kang) Cancer 2012
SBRT as local salvage after incomplete TACE achieved 94.6% 2-year local control and 68.7% 2-year OS in inoperable HCC, with promising ORR of 76.6%. These results...
SBRT for Primary HCC (Andolino) Int J Radiat Oncol Biol Phys 2011
Risk-adapted SBRT achieves 90% 2-year local control with excellent OS (67%) in HCC ≤6 cm across both CTP A and B patients, with no grade ≥3 nonhematologic toxicities...
University of Toronto SBRT (Phase I, HCC/iCCA) J Clin Oncol 2008
Individualized 6-fraction SBRT based on NTCP modeling is safe for unresectable HCC and intrahepatic cholangiocarcinoma, with no RILD and acceptable toxicity. Median...

Pancreas - advanced (12)

RASolute 302 N Engl J Med 2026
In previously treated mPDAC, daraxonrasib roughly doubled overall survival versus chemotherapy (13.2 vs 6.6 mo; HR 0.40) with far fewer treatment discontinuations. It...
PANOVA-3 Journal of Clinical Oncology 2025
TTFields combined with gemcitabine/nab-paclitaxel significantly improved OS, pain-free survival, and distant PFS in unresectable LA-PAC with no added systemic...
RET Fusion Pancreatic Cancer (KRAS-WT): Repotrectinib and Precision Oncology Cancers 2025
Comprehensive genomic profiling is essential in PDAC to identify fusion-driven disease (enriched in KRAS-WT tumors). Targeted therapies offer a precision approach for...
SEQUENCE trial NEJM Evid 2024
Upfront nab-paclitaxel/gemcitabine followed by mFOLFOX significantly improved 12-month and median survival versus standard nab-paclitaxel/gemcitabine in metastatic...
NAPOLI-3 Lancet 2023
NALIRIFOX significantly improved OS and PFS compared to nab-paclitaxel+gemcitabine in previously untreated metastatic PDAC (OS 11.1 vs 9.2 months, HR 0.83, P=.036)...
LAPACT Lancet Gastroenterol Hepatol 2020
nab-Paclitaxel + gemcitabine demonstrated activity in LAPC with a disease control rate of 77.6%, mPFS of 10.9 months, and mOS of 18.8 months. 16% of patients achieved...
POLO Trial NEJM 2019
Maintenance olaparib significantly prolonged PFS versus placebo in germline BRCA-mutated metastatic pancreatic cancer that had not progressed on first-line platinum...
FOLFIRINOX Meta-analysis for LAPC (Suker) Lancet Oncol 2016
FOLFIRINOX achieved a pooled mOS of 24.2 months in LAPC - substantially longer than prior gemcitabine-based therapies (~8-13 months) and comparable to historical OS...
NAPOLI 1 Study Lancet 2016
Nanoliposomal irinotecan plus 5-FU/folinic acid improved survival versus 5-FU/folinic acid alone in patients with metastatic pancreatic adenocarcinoma previously...
MPACT N Engl J Med 2013
nab-Paclitaxel + gemcitabine significantly improved OS (8.5 vs 6.7 months, HR 0.72), PFS, and response rate versus gemcitabine alone in metastatic pancreatic cancer...
FOLFIRINOX for Metastatic Pancreatic Cancer (ACCORD 11) N Engl J Med 2011
FOLFIRINOX nearly doubled OS versus gemcitabine in fit patients with metastatic pancreatic cancer (11.1 vs 6.8 months, HR 0.57), with substantially higher response...
Gemcitabine VS 5-FU TRIAL JCO 1997
Gemcitabine provided superior clinical benefit response and a modest survival advantage over bolus 5-FU, establishing it as a first-line standard for advanced...

Anal (11)

ACT-II (Post-Hoc 5-Year) Lancet Oncol 2017
At 5-year follow-up, MMC and cisplatin have equivalent PFS and OS when used concurrently with 5-FU-based CRT. Maintenance 5-FU + cisplatin provides no benefit in any...
Goodman Capecitabine vs 5-FU IMRT Int J Radiat Oncol Biol Phys 2017
Substituting oral capecitabine for infusional 5-FU with MMC and IMRT significantly reduces grade 3-4 neutropenia (52% → 20%) and treatment delays (42% → 16%)...
Meta-analysis TACE+SBRT vs TACE for HCC (Huo) JAMA Oncol 2015
Meta-analysis demonstrates that TACE combined with SBRT significantly improves overall survival and local control compared to TACE alone for HCC, supporting the...
Watch and Wait Meta-analysis (Renehan) Lancet Oncol 2016
Non-operative watch-and-wait management in rectal cancer patients achieving cCR after preoperative CRT is oncologically safe, with 5-year OS ~88% and a local regrowth...
RTOG 0529 Int J Radiat Oncol Biol Phys 2013
Dose-painted IMRT significantly reduced acute hematologic, GI, and dermatologic toxicities compared to historical 3D-CRT (RTOG 9811) while maintaining locoregional...
ACCORD-III JCO 2012
Dose escalation with cisplatin induction followed by cisplatin + 60 Gy RT did not improve colostomy-free survival or OS compared with standard 5-FU + MMC + 45-59 Gy...
Adjuvant Therapy Biliary Tract Cancer Meta-analysis (Horgan) J Clin Oncol 2012
Adjuvant therapy (particularly CT or CRT) shows a significant survival benefit for biliary tract cancer in patients with lymph node-positive and R1-resected disease...
RTOG 9811 (Long-Term) J Clin Oncol 2012
At long-term follow-up, MMC-based CRT was superior to cisplatin induction followed by cisplatin-concurrent CRT for both DFS and OS in anal canal carcinoma, confirming...
EORTC 22861 J Clin Oncol 1997
CRT with 5-FU and mitomycin C significantly improved complete response, locoregional control, and colostomy-free survival compared with RT alone in locally advanced...
Intergroup (RTOG/ECOG) J Clin Oncol 1996
Despite greater toxicity, addition of mitomycin C to 5-FU-based CRT significantly improved colostomy-free survival and DFS in anal canal cancer, confirming MMC as an...
UKCCR Anal Cancer Trial 1996
Chemoradiation with 5-FU and mitomycin C significantly reduces local failure and anal cancer-specific death compared with radiation alone, establishing CRT as the...

NET - advanced (11)

COMPETE trial Lancet 2026
First-line/progressive PRRT with [177Lu]Lu-edotreotide significantly prolonged PFS versus everolimus in SSTR-positive grade 1-2 GEP-NET, with a lower overall...
NETTER-2 Lancet 2024
First-line [177Lu]Lu-DOTATATE plus octreotide LAR significantly prolonged PFS by a median of 14 months versus high-dose octreotide in higher-grade G2-G3 SSTR-positive...
SPINET Endocr Relat Cancer 2024
SPINET is the largest prospective study of SSA therapy in SSTR-positive bronchopulmonary NETs. Despite early enrollment termination and an underpowered comparison...
NETTER-1 Trial NEJM 2017
177Lu-Dotatate markedly improved PFS over high-dose octreotide LAR in progressive metastatic midgut neuroendocrine tumors, establishing peptide receptor radionuclide...
TELESTAR JCO 2017
Telotristat ethyl at 250 mg and 500 mg TID significantly reduced BM frequency and urinary 5-HIAA in carcinoid syndrome patients not adequately controlled by SSA. The...
RADIANT 4 trial Lancet 2016
Everolimus significantly prolonged PFS versus placebo in advanced, progressive, non-functional lung and GI neuroendocrine tumors, with a manageable safety profile.
CLARINET trial, lancreotide vs pbo NEJM 2014
In advanced nonfunctioning enteropancreatic neuroendocrine tumors, lanreotide significantly prolonged progression-free survival versus placebo.
NORDIC NEC Ann Oncol 2013
Platinum-based chemotherapy prolongs survival dramatically versus BSC in advanced GI-NEC (11 vs 1 month). Ki-67 is simultaneously predictive and prognostic: patients...
RADIANT-3 NEJM 2011
Everolimus 10 mg significantly prolonged PFS in progressive advanced pNET (11.0 vs 4.6 months, HR 0.35, P<.001). RADIANT-3 established everolimus as a standard of...
SUNITINIB NET, sun vs pbo NEJM 2011
Continuous daily sunitinib significantly improved PFS versus placebo in advanced, progressing well-differentiated pancreatic neuroendocrine tumors, establishing it as...
PROMID trial, octreotide vs pbo JCO 2009
In metastatic midgut neuroendocrine tumors, octreotide LAR significantly prolonged time to progression, establishing an antiproliferative role for somatostatin analogs.

Pancreatic (10)

NRG Oncology/RTOG 0848 J Clin Oncol 2026
Adding adjuvant chemoradiotherapy to adjuvant chemotherapy did not improve overall survival or DFS, and did not raise grade 4/5 toxicity, in resected pancreatic head...
Murphy Total Neoadjuvant Therapy BRPC/LAPC JAMA Oncol 2018
Total neoadjuvant gemcitabine/nab-paclitaxel followed by SBRT for borderline resectable pancreatic cancer is feasible and achieves promising R0 resection rates (78%...
Alliance A021101 JAMA Surg 2016
Preoperative mFOLFIRINOX followed by SBRT and resection for borderline resectable pancreatic cancer is feasible, with 93% R0 resection rates in those who underwent...
LAP07 JAMA 2016
CRT after induction gemcitabine in LAPC did not improve OS vs continued chemotherapy (15.2 vs 16.5 months, P=.83), despite significantly improving local PFS....
SBRT Phase II Multi-Institutional (Herman) Cancer 2015
SBRT (33 Gy in 5 fractions) after one cycle of gemcitabine achieves 78% freedom from local progression at 1 year with 13.9-month mOS and acceptable late GI toxicity...
ECOG E4201 J Clin Oncol 2011
Gemcitabine-based CRT showed a statistically significant OS benefit over gemcitabine alone in locally advanced pancreatic cancer (11.1 vs 9.2 months, P=.017), but...
RTOG 9704 Ann Surg Oncol 2011
Gemcitabine-based adjuvant therapy trended toward improved survival versus 5-FU, particularly in pancreatic head tumors (HR 0.82), but did not reach statistical...
Borderline Resectable Pancreatic Cancer (Katz) J Am Coll Surg 2008
Anatomic criteria-based classification of borderline resectable pancreatic cancer and aggressive preoperative therapy followed by surgery can achieve high R0...
GERCOR Retrospective (Huguet) J Clin Oncol 2007
Sequential CRT after induction chemotherapy for LAPC was associated with significantly improved OS (15.0 vs 11.7 months) and PFS (10.8 vs 7.4 months) vs continued...
Gastrointestinal Tumor Study Group 9173 Arch Surg 1985
Adjuvant CRT significantly improved OS compared to observation in resected pancreatic cancer (20 vs 11 months), establishing the concept that adjuvant therapy...

Biliary - advanced (7)

FIGHT-302 trial J Clin Oncol 2026
First-line pemigatinib significantly prolonged PFS and roughly tripled ORR vs gemcitabine/cisplatin in FGFR2-rearranged cholangiocarcinoma - the largest randomized...
Keynote 966 2023
Adding pembrolizumab to gemcitabine and cisplatin significantly improved OS versus chemotherapy alone in advanced biliary tract cancer, with a manageable and...
TOPAZ-1 NEJM Evid 2022
Durvalumab plus gemcitabine-cisplatin significantly improved OS compared to gemcitabine-cisplatin alone (HR 0.80, P=.021) in previously untreated advanced biliary...
ABC-06 Lancet Oncol 2021
FOLFOX plus active symptom control significantly improved OS compared to active symptom control alone (HR 0.69, P=.031) in advanced biliary tract cancer after...
ClarIDHy trial Lancet Oncol 2020
Ivosidenib significantly improved PFS and, after crossover adjustment, OS in previously treated IDH1-mutant cholangiocarcinoma, with a tolerable safety profile.
FIGHT-202 Lancet Oncol 2020
Pemigatinib produced a 35.5% ORR with durable responses (mDOR 7.5 months) in previously treated cholangiocarcinoma with FGFR2 fusions or rearrangements, with 0% ORR...
ABC-02 NEJM 2010
Gemcitabine plus cisplatin significantly improved OS and PFS compared to gemcitabine alone (OS 11.7 vs 8.1 months, HR 0.64, P<.001) in advanced biliary tract cancer...

Colon - perioperative (7)

CAIRO6 trial Lancet Oncol 2026
Perioperative systemic therapy did not improve overall survival in resectable colorectal peritoneal-only metastases and added morbidity. It cannot be recommended for...
FOXTROT trial JCO 2023
In patients with operable, locally advanced colon cancer, neoadjuvant FOLFOX improved 2-year disease control without increasing surgical complications. Addition of...
New-EPOC trial 2023
Adding cetuximab to perioperative chemotherapy in operable KRAS wild-type colorectal liver metastases significantly shortened PFS and should not be used in this setting.
RAPIDO trial 2021
Short-course radiotherapy followed by preoperative chemotherapy and TME reduced disease-related treatment failure vs standard long-course chemoradiotherapy in...
UNICANCER-PRODIGE 23 Lancet Onc 2021
Neoadjuvant FOLFIRINOX followed by chemoradiotherapy improved 3-year disease-free survival and pathologic complete response versus standard preoperative...
EORTC 40983 Lancet 2008
Perioperative FOLFOX4 produced a significant PFS benefit in eligible resected patients (HR 0.73, P=.025) and a borderline-significant benefit in the intent-to-treat...
MOSAIC trial NEJM 2004
Adjuvant FOLFOX4 significantly improved disease-free survival versus 5-FU/LV in resected stage II-III colon cancer, with benefit driven predominantly by stage III...

Esophageal - advanced (7)

CheckMate 648 (5-year update) Ann Oncol 2026
At 5 years' minimum follow-up, both nivolumab + chemotherapy and nivolumab + ipilimumab maintain clinically meaningful OS benefit over chemotherapy in 1L advanced...
SKYSCRAPER-07 trial Ann Oncol 2026
The primary comparison (atezolizumab+tiragolumab vs placebo) was NOT met. However, atezolizumab monotherapy consolidation after dCRT significantly improved OS and PFS...
CheckMate 648 NEJM 2022
Both nivolumab combinations significantly improved OS vs chemotherapy in advanced esophageal SCC. Nivolumab + chemotherapy demonstrated a particularly large OS...
KEYNOTE-590 Lancet 2021
First-line pembrolizumab plus chemotherapy improved overall and progression-free survival across all analyzed subgroups versus chemotherapy alone in advanced...
KEYNOTE 181 Trial JCO 2020
Pembrolizumab improved OS over chemotherapy in previously treated advanced esophageal cancer with PD-L1 CPS≥10, with a more favorable safety profile, supporting...
ATTRACTION-3 Trial Lancet Oncol 2019
Nivolumab significantly improved OS over taxane chemotherapy with a favorable safety profile in previously treated advanced esophageal squamous cell carcinoma...
ATTRACTION 2 TRIAL Lancet 2017
Nivolumab improved OS versus placebo in heavily pretreated advanced gastric/GEJ adenocarcinoma, with durable benefit and a manageable safety profile.

Gastric (7)

SOX ± RT after D2 Gastrectomy JAMA Netw Open 2026
Adding postoperative radiotherapy to adjuvant SOX chemotherapy did not improve DFS or OS in T4/node-positive gastric cancer after D2 gastrectomy. The findings do not...
CRITICS Lancet Oncol 2018
Postoperative chemoradiotherapy did not improve OS compared to postoperative chemotherapy in resectable gastric cancer treated with adequate preoperative chemotherapy...
ARTIST Trial J Clin Oncol 2015
Adjuvant chemoradiotherapy did not significantly improve DFS or OS compared to chemotherapy alone in D2-resected gastric cancer overall. However, exploratory subgroup...
Gastric Lymph Node Contouring Atlas Pract Radiat Oncol 2012
Provides a standardized CT-based contouring template for gastric lymph node stations applicable to all major surgical resection types, enabling consistent and...
RTOG 9904 J Clin Oncol 2006
Preoperative chemoradiotherapy with induction FLC followed by concurrent 5-FU/paclitaxel + 45 Gy achieved a 26% pCR rate - exceeding the hypothesized 20% threshold...
Intergroup 0116 N Engl J Med 2001
Adjuvant chemoradiotherapy (5-FU/LV + 45 Gy) after curative resection significantly improved OS and RFS compared to observation in high-risk gastric cancer, with...
Dutch D2 Dissection Trial N Engl J Med 1999
In Dutch hospitals, D2 dissection offered no OS benefit over D1 at 5 years and significantly increased perioperative morbidity and mortality. However, this result...

GIST - metastatic (7)

Avapritinib/NAVIGATOR trial Lancet Oncol 2020
Avapritinib produced deep, durable responses in advanced GIST with PDGFRA exon 18 (including D842V) mutations, a population without effective standard TKI therapy.
INVICTUS trial Lancet Oncol 2020
Ripretinib significantly improved PFS and OS versus placebo in GIST that had progressed on at least three prior TKIs, with a manageable safety profile.
Regorafenib trial Lancet 2013
Regorafenib significantly improved PFS versus placebo in GIST that had progressed on imatinib and sunitinib, establishing it as standard third-line therapy.
MetaGIST group trial 2010
Imatinib 800mg/day yields a small PFS advantage but no OS benefit over 400mg/day overall; the gain is driven by KIT exon 9-mutant tumors, supporting mutation-guided...
US Intergroup trial, SWOG0033/CLAGB1501105 JCO 2008
High-dose imatinib (800mg/day) did not provide a clinically or statistically significant improvement over 400mg/day in metastatic GIST; dose escalation at progression...
Sunitinib trial Lancet 2006
Sunitinib significantly prolonged TTP and overall survival versus placebo in imatinib-resistant/intolerant GIST, establishing it as standard second-line therapy.
EORTC 62005 trial Lancet 2004
Response rates were similar, but 800mg/day modestly improved PFS over 400mg/day at the cost of more toxicity; benefit was later shown to concentrate in KIT exon...

Anal - advanced (6)

POD1UM-303 / InterAACT-2: Final OS Analysis Ann Oncol 2026
The final analysis confirms a clinically meaningful, durable benefit of adding retifanlimab to carboplatin-paclitaxel as first-line treatment of inoperable, locally...
POD1UM-303 Lancet 2025
Retifanlimab plus carboplatin+paclitaxel significantly improved both PFS (HR 0.63, P=.0006) and OS (HR 0.68, P=.006) compared to carboplatin+paclitaxel alone in...
InterAACT JCO 2020
Carboplatin+paclitaxel and cisplatin+5-FU produced similar 12-week disease control rates (primary endpoint not met) but carbo+pac was associated with significantly...
ACT II Lancet Oncol 2013
MMC and cisplatin concurrent with 5-FU+radiotherapy produced equivalent complete response rates at 26 weeks in anal canal SCCA (94.5% vs 90.5%, P=.074). Maintenance...
RTOG 98-11 trial, mitomycin vs cis 2008
In anal canal carcinoma excluding T1/M1 disease, mitomycin-based chemoradiotherapy yielded better disease-free survival and lower colostomy rate than cisplatin-based...
Nigro regiment Cancer 1983
Concurrent 5-FU/mitomycin-C chemoradiation produced high complete response rates in anal squamous cell carcinoma, leading the authors to conclude that routine...

Biliary - adjuvant (5)

ASCOT (JCOG1202) 5-year follow-up JCO 2026
With 5 years of follow-up, adjuvant S-1 continues to improve OS over observation after resection of biliary tract cancer (5-year OS 64% vs 52%; HR 0.72), with median...
GOLP (ZSAB-neoGOLP) New England Journal of Medicine 2026
Neoadjuvant GOLP followed by surgery significantly prolonged EFS and improved OS versus surgery alone in high-risk resectable intrahepatic cholangiocarcinoma...
ASCOT/JCOG1202 Lancet 2023
Adjuvant S-1 significantly improved OS compared to observation in R0-resected biliary tract cancer, with a 10-percentage-point improvement in 3-year OS (77.1% vs...
BILCAP Lancet Oncol 2019
Although BILCAP did not meet its primary ITT endpoint, the prespecified per-protocol and sensitivity analyses both showed statistically significant OS improvement...
PRODIGE 12 JCO 2019
Adjuvant GEMOX chemotherapy did not improve RFS or OS compared with observation in resected biliary tract cancer (HR 0.88, P=.48). The trial was underpowered and...

Pancreas - adjuvant (5)

APACT J Clin Oncol 2023
APACT did not meet its primary endpoint of independently assessed DFS (HR 0.88, P=.18) despite a statistically significant 5-year OS benefit (HR 0.80, P=.0091)....
ESPAC-4 Lancet 2017
Gemcitabine + capecitabine significantly improved OS versus gemcitabine alone (HR 0.82, P=.032), with a 12.5% 5-year OS benefit (28.8% vs 16.3%). This combination...
CONKO-001 JAMA 2013
Adjuvant gemcitabine significantly improved DFS and long-term OS versus observation after resection. The ~10% 5-year OS benefit (20.7% vs 10.4%) established...
ESPAC-3 JAMA 2010
Gemcitabine and 5-FU/LV were equivalent in OS after resection. Given superior tolerability and quality of life, gemcitabine became the preferred adjuvant agent...
ESPAC-1 N Engl J Med 2004
Adjuvant chemotherapy (5-FU/LV) significantly improved survival in resected pancreatic cancer, while adjuvant chemoradiotherapy had a statistically significant...

Pancreas - perioperative (5)

SWOG 1505 trial JAMA Onc 2021
Neither perioperative mFOLFIRINOX nor gemcitabine/nab-paclitaxel met the prespecified 2-year survival threshold versus historical control in resectable pancreatic...
ESPAC-5F ASCO 2020
In borderline resectable pancreatic cancer, neoadjuvant therapy did not increase the resection rate but markedly improved 1-year survival versus immediate surgery...
NEONAX trial Ann Oncol 2023
Perioperative gemcitabine/nab-paclitaxel was well tolerated, with encouraging mOS in the perioperative arm. The primary 18-mo DFS target of 55% was not reached in...
PRODIGE 24 NEJM 2018
Modified FOLFIRINOX significantly improved DFS and OS compared to gemcitabine as adjuvant therapy after resection of pancreatic ductal adenocarcinoma, with a...
GITSG trial 1985
First randomized trial to show a survival benefit from adjuvant 5-FU-based chemoradiation after R0 resection of pancreatic cancer, establishing a role for...

Esophageal - perioperative (4)

ESOPEC NEJM 2025
Perioperative FLOT significantly improved OS versus neoadjuvant CROSS in resectable esophageal/GEJ adenocarcinoma (mOS 66 vs 37 months, HR 0.70). ESOPEC establishes...
RTOG1010 Trial, chemoRT +/- trastuzumab Lancet Onc 2022
Adding trastuzumab to neoadjuvant chemoradiotherapy did not improve disease-free survival in HER2-overexpressing esophageal adenocarcinoma; outcomes were similar with...
Checkmate 577 NEJM 2021
Adjuvant nivolumab significantly doubled disease-free survival versus placebo in patients with residual pathologic disease after neoadjuvant chemoradiotherapy and...
CROSS Trial NEJM 2012
Neoadjuvant carboplatin/paclitaxel chemoradiation followed by surgery significantly improved overall survival versus surgery alone in resectable esophageal and GE...

GIST - adjuvant (3)

Intergroup EORTC 62024 trial JCO 2015
Adjuvant imatinib delayed recurrence (improved RFS) but did not improve overall survival or imatinib failure-free survival, consistent with high salvage rates with...
SSG XVIII trial JAMA 2012
3 years of adjuvant imatinib is superior to 1 year for both RFS and OS in high-risk resected GIST, with durable benefit at 10 years.
ACOSOG Z9001 trial 2009
1 year of adjuvant imatinib significantly prolonged RFS after complete resection of primary KIT-positive GIST, establishing adjuvant TKI therapy in this setting.

HCC - adjuvant (3)

CARES-009 Lancet 2025
Perioperative camrelizumab plus rivoceranib significantly improved EFS and OS in resectable HCC at intermediate-to-high recurrence risk, with...
IMbrave050 Lancet 2023
Adjuvant atezolizumab plus bevacizumab significantly improved recurrence-free survival versus active surveillance in high-risk resected or ablated HCC, the first...
STORM Lancet Oncol 2015
Adjuvant sorafenib did not improve recurrence-free survival after curative resection or ablation of HCC. This large phase III trial definitively established that...

Biliary (2)

SBRT for Cholangiocarcinoma (Sandler) Adv Radiat Oncol 2016
SBRT for both extrahepatic and intrahepatic cholangiocarcinoma achieves reasonable 1-year local control (73-78%) with acceptable toxicity. Outcomes are better for...
SWOG S0809 (Adjuvant CRT for eCCA/GBC) J Clin Oncol 2015
Adjuvant gem/cap followed by CRT achieved 65% 2-year OS (median 35 months) in resected eCCA/GBC, exceeding the predefined threshold, with R0 and R1 patients achieving...

Gastric - adjuvant (1)

CLASSIC Lancet Oncol 2014
Adjuvant CAPOX significantly improved 5-year DFS (68% vs 53%) and OS (78% vs 69%) after D2 gastrectomy in stage II-IIIB gastric cancer, confirming durable benefit of...