Trials · Topics · Head and Neck Cancer
Head and Neck Cancer clinical trials
78 Head and Neck 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: Locoregional - concurrent CRT · Nasopharyngeal · Thyroid cancer · Recurrent/metastatic · HPV+ locoregional · Larynx / Hypopharynx · Oropharynx · Salivary · Thyroid · Locoregional - induction · Nasopharynx · Oral cavity / oropharynx · Workup / guidelines · Salivary Gland Cancer · Sinonasal · Locoregional - adjuvant CRT · Unknown primary
Locoregional - concurrent CRT (10)
- ConCERT trial J Natl Cancer Inst 2026Weekly low-dose cisplatin chemoradiation was noninferior to 3-weekly high-dose cisplatin for 2-year locoregional control in non-nasopharyngeal LA-HNSCC, with...
- JCOG1008 long-term follow-up J Clin Oncol 2026Mature 5-year follow-up of JCOG1008 confirms noninferior long-term overall survival with weekly cisplatin chemoradiotherapy versus standard 3-weekly cisplatin in...
- KEYNOTE-689 NEJM 2025Perioperative pembrolizumab significantly improved EFS (HR 0.73) in high-risk resected LA-HNSCC, with greater benefit in PD-L1 CPS ≥1 (HR 0.67) and CPS ≥10 (HR 0.59)....
- KEYNOTE-412 Lancet Oncol 2024Adding pembrolizumab to definitive or adjuvant CRT did not significantly improve EFS in unselected LA-HNSCC (HR 0.83, P=.066). The trial was negative for its primary...
- JCOG1008, cisplatin q3wk vs q1wk JCO 2022Weekly cisplatin chemoradiotherapy was noninferior to standard 3-weekly cisplatin for OS in patients with postoperative high-risk LA-SCCHN, with less neutropenia...
- Javelin Head and Neck 100 Lancet Oncol 2021Adding avelumab to standard cisplatin-based chemoradiation, with maintenance, did not improve progression-free survival in locally advanced HNSCC; the trial was...
- MACH-NC mena-analysis J of Radiother Oncol 2021MACH-NC confirmed the OS benefit of concurrent chemoradiotherapy for locally advanced head and neck SCC over locoregional therapy alone and over induction followed by...
- Cisplantin q3wk vs q1wk by Tata Memorial JCO 2018Once-every-3-weeks cisplatin 100 mg/m2 produced superior locoregional control, albeit with more toxicity, than once-weekly cisplatin 30 mg/m2. Treatment compliance...
- RTOG 0129 NEJM 2010Standard and accelerated concomitant boost fractionation with cisplatin produced equivalent survival. The pivotal finding: HPV positivity (p16+ surrogate) conferred...
- Bonner NEJM 2006Adding cetuximab to RT significantly prolonged locoregional control (HR 0.68) and OS (HR 0.74, mOS 49 vs 29 mo) without increasing radiation-related toxicity in...
Nasopharyngeal (9)
- Magic-M001 Ann Oncol 2026In heavily pretreated, immunotherapy-exposed R/M nasopharyngeal carcinoma, becotatug vedotin nearly tripled ORR and significantly improved PFS vs chemotherapy, with...
- TPC vs PF induction (LA-NPC) NEJM Evid 2026In high-risk LA-NPC, TPC induction produced durable improvements in 5-year FFS, distant metastasis-free, locoregional relapse-free, and overall survival versus PF...
- Izalontamab brengitecan (iza-bren) Lancet 2025Izalontamab brengitecan, a bispecific EGFR/HER3 ADC, significantly improves ORR in heavily pretreated recurrent/metastatic NPC, with 27.9% absolute response benefit....
- RATIONALE-309 Cancer Cell 2023Tislelizumab + gemcitabine-cisplatin significantly improved PFS (HR 0.52) with 1-year PFS of 57% vs 25% vs placebo + GP in first-line R/M NPC. Results are consistent...
- CAPTAIN-1st Lancet Oncol 2021Camrelizumab + GP significantly improved PFS (HR 0.54) and OS (HR 0.55) vs placebo + GP as first-line treatment for R/M NPC. CAPTAIN-1st was the first phase III trial...
- JUPITER 02 Nature 2021Adding toripalimab to first-line gemcitabine/cisplatin significantly improved PFS and OS in recurrent or metastatic nasopharyngeal carcinoma without adding...
- Gem/Cis/IMRT vs NEJM 2019Gemcitabine/cisplatin induction chemotherapy added to standard concurrent chemoradiotherapy significantly improved 3-year recurrence-free and overall survival in...
- Sun 2016 Lancet Oncol 2016TPF induction chemotherapy followed by concurrent CRT significantly improved 3-year failure-free survival (80% vs 72%, HR 0.68) compared to CRT alone in...
- Intergroup 0099 JCO 1998Cisplatin-based concurrent CRT followed by adjuvant cisplatin-fluorouracil dramatically improved PFS (69% vs 24%) and OS (78% vs 47%) at 3 years vs RT alone in LA...
Thyroid cancer (8)
- LIBRETTO-001 (thyroid) JCO 2024Selpercatinib achieved ORRs of 69-79% across RET-mutant MTC and RET fusion-positive thyroid cancer - substantially higher than vandetanib (45%) or cabozantinib (28%)...
- ROAR ATC Ann Oncol 2022Dabrafenib + trametinib achieved a 56% ORR - the highest ORR reported for any systemic therapy in BRAF V600E ATC - with a median OS of 14.5 months vs historical <6...
- ARROW (thyroid) Lancet Diabetes Endocrinol 2021Pralsetinib achieved confirmed ORRs of 60-89% across RET-mutant MTC (pretreated and naive) and RET fusion-positive thyroid cancer. Results are consistent with...
- COSMIC 311 Lancet Onc 2021In patients with radioiodine-refractory DTC who progressed after prior VEGFR-targeted therapy, cabozantinib significantly prolonged PFS versus placebo, providing a...
- SELECT trial, Lenvatinib 2nd line NEJM 2015Lenvatinib significantly improved progression-free survival and response rate versus placebo in progressive, radioactive-iodine-refractory differentiated thyroid...
- DECISION Lancet 2014Sorafenib significantly improved PFS by 5 months (HR 0.59) vs placebo in RAI-refractory DTC, with an ORR of 12.2% (partial responses) and high disease stabilization...
- EXAM JCO 2013Cabozantinib dramatically improved PFS (HR 0.28, median 11.2 vs 4.0 months) and achieved a 28% ORR in progressive MTC regardless of RET mutation status. EXAM led to...
- ZETA JCO 2012Vandetanib significantly improved PFS (HR 0.46) and ORR (45% vs 13%) with calcitonin tumor marker reduction in 69% of patients. The PFS median was not reached in the...
Recurrent/metastatic (6)
- CheckMate 651 JCO 2023Nivolumab + ipilimumab did not formally meet its primary endpoint of superior OS vs EXTREME in PD-L1 TPS ≥20% R/M HNSCC due to hierarchical testing failure (P=.0469...
- KEYNOTE-040 trial Lancet 2019Pembrolizumab prolonged overall survival versus standard-of-care chemotherapy in platinum-pretreated recurrent or metastatic HNSCC, with greater benefit in...
- KEYNOTE-048 Lancet 2019Pembrolizumab plus platinum and 5-FU significantly improved overall survival in the total population, and pembrolizumab monotherapy improved OS in PD-L1 CPS-positive...
- CHECKMATE 141, nivo vs chemo in 2nd line NEJM 2016Nivolumab significantly improved overall survival versus standard single-agent therapy in platinum-refractory recurrent HNSCC, with benefit most pronounced in PD-L1...
- EXTREME trial, Cis/5FU +/- Cetuximab NEJM 2008Adding cetuximab to platinum-fluorouracil chemotherapy improved overall survival, progression-free survival, and response rate in first-line recurrent or metastatic...
- TAX 323 trial, TPF vs PF induction NEJM 2007Induction chemotherapy with TPF significantly improved both PFS and OS compared with PF in unresectable locoregionally advanced SCCHN, with a lower rate of...
HPV+ locoregional (5)
- ECOG E3311 JCO 2022TOS followed by risk-adapted adjuvant therapy yielded outstanding 2-year PFS (91-97%) in HPV+ OPC with excellent functional preservation, especially de-intensified 50...
- NRG-HN002 JCO 2021Both reduced-dose arms (60 Gy) yielded outstanding 2-year PFS (>87%) and OS (>96%) in low-risk HPV+ OPC. NRG-HN002 recommended Arm A (chemoRT 60 Gy) for phase III...
- De-ESCALaTE HPV Lancet 2019Cetuximab did not reduce severe toxicity vs cisplatin (equivalence met) but was significantly inferior for OS and tumor control. Cisplatin remains the standard...
- RTOG 1016 Lancet 2019Cetuximab + IMRT was inferior to cisplatin + IMRT for OS and PFS in HPV+ oropharyngeal SCC and failed to meet the non-inferiority threshold. Cisplatin-based CRT...
- ECOG E1308 JCO 2017Induction chemotherapy followed by de-escalated IMRT (54 Gy) + cetuximab yielded excellent 2-year PFS (80%) and OS (94%) in patients achieving ≥PR, with substantially...
Larynx / Hypopharynx (5)
- Mohamed 2019 (IMRT vs 3D-CRT T1 Larynx) Laryngoscope 2019IMRT for T1 glottic larynx cancer can reduce dose to adjacent critical structures (arytenoids, contralateral vocal cord) vs 3D-CRT while maintaining excellent local...
- RTOG 9111 J Clin Oncol 2013Concurrent cisplatin-RT provides the highest rate of larynx preservation compared with induction chemotherapy followed by RT or RT alone. Both chemotherapy-containing...
- Japanese Glottic Cancer Trial (Yamazaki 2006) Int J Radiat Oncol Biol Phys 2006Slightly hypofractionated RT (2.25 Gy/fraction over a shorter overall treatment time) significantly improved 5-year local control for T1N0M0 glottic carcinoma (92% vs...
- EORTC 24891 J Natl Cancer Inst 1996Larynx preservation using induction cisplatin/5-FU followed by definitive radiotherapy for complete responders achieves equivalent survival to conventional surgery +...
- VA Larynx Study 1991Induction chemotherapy followed by definitive radiotherapy achieves equivalent survival to standard total laryngectomy in advanced laryngeal cancer, while preserving...
Oropharynx (5)
- ORATOR Lancet Oncol 2019RT achieved superior 1-yr swallowing QoL vs TORS + neck dissection for T1-T2 OPSCC, though the 86.9 vs 80.1 difference did not meet the prespecified 10-point clinical...
- ASTRO Oropharyngeal Cancer Guideline 2017 Pract Radiat Oncol 2017The ASTRO 2017 guideline established evidence-based indications for concurrent cisplatin in definitive and adjuvant OPSCC RT, recommended against routine induction...
- IMPT vs IMRT Oropharynx Radiother Oncol 2016IMPT significantly reduced grade ≥3 PEG requirement and acute mucositis compared to IMRT in locally advanced OPSCC, while maintaining equivalent disease control and...
- Ang 2010 (HPV Oropharyngeal Cancer Prognostic) N Engl J Med 2010HPV-positive OPSCC has significantly better OS and PFS than HPV-negative disease after concurrent CRT (3-yr OS 82.4% vs 57.1%). Combined with T/N stage and smoking...
- O'Sullivan 2001 (Princess Margaret Ipsilateral RT) Int J Radiat Oncol Biol Phys 2001Carefully selected well-lateralized tonsillar carcinoma can be safely treated with ipsilateral RT (contralateral neck failure 4.8%) while reducing xerostomia and...
Salivary (5)
- Amini 2016 (Adjuvant CRT vs RT Salivary) JAMA Otolaryngol Head Neck Surg 2016The addition of concurrent chemotherapy to adjuvant RT in resected high-risk major salivary gland carcinoma did not improve overall survival and was associated with...
- UCSF cN0 Parotid Series Int J Radiat Oncol Biol Phys 2007Elective neck irradiation should be considered for high-risk cN0 parotid carcinoma, particularly high-grade histology, advanced T-stage, perineural invasion, or...
- UCSF ACC Series Int J Radiat Oncol Biol Phys 2006Surgery + adjuvant RT is effective for ACC. Perineural invasion warrants extended RT fields covering neural pathways. Distant failure remains the major challenge...
- NWHHT (Terhaard 2005) Int J Radiat Oncol Biol Phys 2005Postoperative RT with ≥60 Gy significantly improved local and regional control for T3-4 salivary gland carcinomas, incomplete/close resections, bone invasion, and...
- UF ACC Series (Mendenhall 2004) Head Neck 2004Surgery + adjuvant RT yields excellent local control (94% at 5 yr) and is optimal for ACC. Selected unresectable disease curable with RT alone. T stage and clinical...
Thyroid (5)
- Dabrafenib + Trametinib in RAI-refractory BRAF+ DTC (NCT04940052) Lancet Oncol 2026Dabrafenib plus trametinib significantly prolonged PFS and markedly increased ORR versus placebo in previously treated RAI-refractory BRAF V600E DTC, with no new...
- Saeed 2020 (Anaplastic Thyroid Cancer CRT) Head Neck 2020Multimodality treatment (surgery, chemoradiotherapy, systemic therapy) can achieve disease control and prolonged survival in selected ATC patients, though prognosis...
- 2015 ATA Thyroid Cancer Guidelines Thyroid 2016The 2015 ATA guidelines provide a comprehensive, risk-stratified framework for thyroid nodules and DTC, emphasizing individualized de-escalation for low-risk disease...
- AHNS EBRT Statement for DTC (Kiess 2016) Head Neck 2016EBRT has a limited but defined role in DTC - adjuvant therapy for unresectable disease, positive/close margins after surgery in high-risk patients, and palliation....
- EBRT for Medullary Thyroid Cancer (Terezakis 2010) J Natl Compr Canc Netw 2010EBRT should be considered for locally advanced MTC to optimize locoregional control - particularly T4 disease, ECE, positive margins, or incomplete resection. Not...
Locoregional - induction (4)
- GORTEC 2000-01 trial, TPF vs PF JNCI 2015In advanced larynx and hypopharynx carcinoma, TPF induction chemotherapy was superior to PF for larynx preservation and overall response, with durable LPR benefit at...
- DeCIDE JCO 2014Induction TPF before CRT did not improve OS, RFS, or distant failure-free survival vs CRT alone in N2/N3 HNSCC. The trial was underpowered due to failure to reach...
- PARADIGM Lancet Oncol 2013Adding TPF induction before CRT did not improve OS vs CRT alone in locally advanced HNSCC (HR 1.09 favoring CRT alone, non-significant). Terminated early for slow...
- TAX 324 trial, TPF vs PF induction NEJM 2007Induction TPF followed by concurrent carboplatin chemoradiation significantly prolonged OS compared with PF induction followed by the same chemoradiation in locally...
Nasopharynx (4)
- Zhang 2019 (Induction GC + CRT NPC) N Engl J Med 2019Induction gemcitabine-cisplatin before concurrent CRT significantly improved FFS and OS in locoregionally advanced NPC, with ~9% 5-yr OS benefit and acceptable...
- RTOG 0225 J Clin Oncol 2009IMRT for NPC achieves excellent 2-yr locoregional control (93.5%) while significantly reducing salivary gland toxicity and xerostomia vs conventional 2D radiotherapy....
- Singapore SQNP01 J Clin Oncol 2005Concurrent + adjuvant chemoradiation improved DFS and OS vs RT alone in endemic (WHO II/III) NPC, confirming INT 0099 in a Southeast Asian population; distant...
- INT 0099 J Clin Oncol 1998Concurrent cisplatin chemoradiotherapy plus adjuvant cisplatin/5-FU significantly improved PFS and OS vs RT alone for advanced NPC, establishing concurrent...
Oral cavity / oropharynx (3)
- EORTC 22931/RTOG 9501 Combined Analysis Head Neck 2005The pooled analysis clarified that microscopically involved resection margins and extracapsular spread from neck nodes are the strongest indications for...
- RTOG 9501 N Engl J Med 2004Postoperative concurrent cisplatin + radiotherapy significantly improved locoregional control and DFS compared with radiotherapy alone in high-risk resected head and...
- Ang 2001 (Post-Op RT Risk Factors & Time) Int J Radiat Oncol Biol Phys 2001Pathologic risk features reliably predict need and dose of PORT. Overall surgery-plus-PORT duration significantly impacts LRC and survival-a prolonged surgery-to-PORT...
Workup / guidelines (3)
- Galloway 2015 (SCCUP Management Review) J Clin Oncol 2015SCCUP is increasingly an HPV-related disease with an occult oropharyngeal primary. Modern multimodality treatment with comprehensive staging (TORS/bilateral...
- Cianchetti 2009 (Occult Primary Workup) Laryngoscope 2009The most common occult primary sites are the tonsillar fossa and base of tongue (combined 88.6% of identified primaries). Tonsillectomy identified the primary in 44%...
- Koch 2001 (Bilateral Tonsillectomy Unknown Primary) Otolaryngol Head Neck Surg 2001Because up to 10% of occult tonsillar primaries may have contralateral spread, bilateral tonsillectomy is recommended as a routine step in the workup of unknown...
Salivary Gland Cancer (2)
- Takahashi HER2+ SDC JCO 2019Trastuzumab + docetaxel achieved an ORR of 70.2% and clinical benefit rate of 84.2% with a median OS of 39.7 months in HER2-positive SDC, representing the best...
- Fushimi CAB (AR+ SDC) Ann Oncol 2018Combined androgen blockade with leuprorelin + bicalutamide achieved a 41.7% ORR, 75% clinical benefit rate, and 30.5-month median OS in AR-positive SDC - outcomes...
Sinonasal (2)
- Madani 2009 (IMRT Sinonasal Tumors) Int J Radiat Oncol Biol Phys 2009IMRT for sinonasal tumors achieves 5-yr local control of 70.7% and eliminates radiation-induced blindness vs historical 2D techniques; cribriform plate invasion is...
- Bristol 2007 (Post-Op RT Maxillary Sinus) Int J Radiat Oncol Biol Phys 2007Elective neck RT for squamous histology and improved dose distribution significantly improved nodal control, reduced distant metastasis, and markedly decreased late...
Locoregional - adjuvant CRT (1)
- EORTC 22931 NEJM 2004Post-operative CRT with cisplatin significantly improved PFS, OS, and locoregional control vs RT alone in resected high-risk HNSCC. EORTC 22931 showed a stronger...
Unknown primary (1)
- Shoushtari 2011 (IMRT Unknown Primary) Int J Radiat Oncol Biol Phys 2011IMRT for head and neck CUP maintains high locoregional control while reducing late xerostomia vs conventional whole-mucosal RT, by sparing at least one parotid gland...