Background
Phase II RCT (CALGB 80803 / Alliance). Phase II randomized pilot study in patients with resectable esophageal or gastroesophageal junction adenocarcinoma using PET to direct induction chemotherapy selection prior to chemoradiotherapy and surgery. Patients received initial FOLFOX chemotherapy; PET response was assessed. PET-non-responders were switched to carboplatin/paclitaxel for the CRT phase; PET-responders continued with FOLFOX-based CRT. Primary endpoint was pathologic complete response (pCR) rate. Results were primarily reported in abstract form (ASCO 2017 and 2018 supplemental).
Interventions and follow up
Arm A: FOLFOX (6 cycles induction) → PET assessment → PET non-responders: switch to carboplatin/paclitaxel + 50.4 Gy → surgery
Arm B: FOLFOX (6 cycles induction) → PET assessment → PET responders: continue FOLFOX + 50.4 Gy → surgery
Primary endpoint: Pathologic complete response (pCR) rate
mFollow up: Data from abstract presentations only
Arm B: FOLFOX (6 cycles induction) → PET assessment → PET responders: continue FOLFOX + 50.4 Gy → surgery
Primary endpoint: Pathologic complete response (pCR) rate
mFollow up: Data from abstract presentations only
Results
pCR rate (PET-non-responders switched to carboplatin/paclitaxel): ~18% (per abstract data)
pCR rate (PET-responders who continued FOLFOX): ~17%
Feasibility: PET-directed adaptive therapy was feasible and acceptable
pCR rate (PET-responders who continued FOLFOX): ~17%
Feasibility: PET-directed adaptive therapy was feasible and acceptable
Adverse events
Main adverse events: Toxicity consistent with prior trials using FOLFOX and carboplatin/paclitaxel. No unexpected safety signals. Surgical complication rates and 30-day mortality within expected ranges for esophagectomy.
Conclusions
PET-directed adaptive chemotherapy for esophageal adenocarcinoma is feasible. The pCR rates with both FOLFOX-based and carboplatin/paclitaxel-based CRT were modest (~17–18%), consistent with historical rates for esophageal adenocarcinoma. Switching to carboplatin/paclitaxel in PET non-responders did not substantially improve pCR rates, suggesting initial FOLFOX non-response predicts lower sensitivity to any regimen.
Key Limitations
Key Limitations: Phase II design — not powered for survival endpoints. Full peer-reviewed publication was not available at time of this entry; data derived from conference abstracts. The concept of PET-directed therapy assumes PET response is a valid surrogate for chemosensitivity and ultimate survival — this has not been validated in esophageal cancer. The trial addresses adenocarcinoma only (not SCC). pCR rates in the 17-18% range are modest; CROSS achieves ~23% pCR in adenocarcinoma.
Clinical Context
CALGB 80803 represents the concept of adaptive, biomarker-directed therapy in esophageal cancer. PET-based response assessment is used clinically to guide decisions but has not been validated as a basis for chemotherapy switching in prospective trials. The ESOPEC trial (2024), comparing CROSS vs FLOT, provides the most current evidence for adenocarcinoma management and is shifting practice toward FLOT perioperative chemotherapy.
References