397 Background: We previously found that adding D to induction FOLFOX and PET-directed CRT in resectable EA was safe and had promising pathologic responses and survival outcomes (Ann Surg 2023;278:e511). Here, we add T to the combination. Methods: Pts with locally advanced (cT3/4 and/or cN+) E/gastroesophageal junction A received 2 cycles of mFOLFOX6. PET responders (≥35% SUV reduction, PETr) received 5-FU/capecitabine + oxaliplatin with RT; PET non-responders (PETnr) received carboplatin/paclitaxel with RT. All received T 300 mg ×1 and D 1500 mg q4W ×2 starting 2 weeks before CRT. Esophagectomy was planned 6–8 weeks post-CRT. R0 resections were followed by adjuvant T 300 mg ×1 and D 1500 mg q4W ×6. Primary endpoint was pathologic complete response (pCR) rate. Results: 20 Pts were enrolled; 1 withdrew before treatment. Median follow-up was 23.9 (21.4–47.5) months. 1 Pt died of aspiration pneumonia while being treated for grade 4 colitis during CRT. Of 18 Pts who completed CRT, 3 achieved clinical complete response (cCR) and declined surgery and 1 Pt developed distant metastases. As such, 14 Pts had surgery. pCR rate was 26% (5/19, ITT) and 36% (5/14) in resected Pts. The combined pCR+cCR rate was 42% (8/19). Major pathologic response (MPR; Notable gd 1/2 adverse events (AEs) included fatigue (63%), nausea (63%), diarrhea (47%) and neutropenia (21%); gd ³3 events comprised neutropenia (16%) and acute kidney injury (5%). Immune-related AEs were rash/dermatitis (37%; gd ³3 11%), pruritus (21%; gd ³3 11%), colitis (21%; gd ³3 16%), arthralgia/arthritis (16%; all gd £2) and thyroid dysfunction (11%, all gd £2). PFS was 84.2% (95%CI 69.3-100.0) and 72.2% (95%CI 54.1-100.0) at 12- and 24-months. OS was 89.5% (95%CI 76.7-100.0) and 82.0% (95%CI 65.2-100.0) at 12- and 24-months, Of the 3 Pts with cCR who declined surgery, 1 relapsed locally at 14.7 months and was salvaged surgically (disease-free at 23.2 months), 1 developed brain/liver metastases at 16.2 months and 1 remains disease-free at 15.9 months. Conclusions: Adding D+T to PET-directed CRT in resectable esophageal/GEJ adenocarcinoma led to encouraging pathologic responses and survival outcomes. However, toxicities were qualitatively increased vs. D plus CRT. Although perioperative chemo is now standard, immunotherapy-based PET-directed CRT may remain relevant in Pts who wish to avoid esophagectomy. Clinical trial information: NCT02962063 .
Choo et al. (Sat,) studied this question.