Survival outcome of E1201: An Eastern Cooperative Oncology Group (ECOG) randomized phase II trial of neoadjuvant preoperative paclitaxel/cisplatin/radiotherapy (RT) or irinotecan/cisplatin/RT in endoscopy with ultrasound (EUS) staged esophageal adenocarcinoma

Abstract

4532 Background: E1201 included operable esophageal adenocarcinoma, staged II-IVa by EUS. The primary endpoint was pathologic complete response (pCR), a surrogate endpoint generally associated with survival. Previously reported pCr rates indicated that these regimens did not meet criteria for further study based on a target of 45% against the null hypothesis of 25% for standard therapy. Sufficient follow-up is now available to report survival outcome. Methods: 86 eligible pts began treatment. Arm A was cisplatin (C) 30mg/m2 and irinotecan (I) 50 mg/m2 on days (d) 1, 8, 22, 29 of 45 Gy RT/5 weeks. Post-op therapy was C 30 mg/m2 and I 65 mg/m2 d 1, 8 q21 days x 3. Arm B therapy was C 30 mg/m2 and paclitaxel (P) 50 mg/m2 1 hour infusion d 1, 8, 15, 22, 29 with RT. Postoperative therapy was C 75 mg/m2 and P 175 mg/m2 day 1 q21 days x 3. Previously reported pCR was 14% for arm A (95% CI [5.5%, 28.5%]) and 16% (95% CI [6.7%, 30.1%]) for arm B. Results: Twenty-two of the 42 eligible and treated patients in Arm A are known to have died. Median survival in Arm A is 34.9 m (months) with a 90% CI of [23.5, NR]. In Arm B, 27 of the 44 eligible and treated patients are known to have died, with one patient having refused follow-up. Median survival in Arm B is 20.9 m with a 90% CI of [17.4, 46.7]. The outcome for the treatment arms was similar. Survival was also assessed by EUS strata. Eleven of the 21 eligible and treated patients in stage stratum one (Stages T2N0M0 or T3N0M0) are known to have died. Median survival in stage stratum one is 36.5 m with a 90% CI of [20.5, NR]. In stage stratum two (Stages T1–3N1M0 or T1–3N0-1M1a), 38 of the 65 eligible and treated patients are known to have died. Median survival is 26.0 m with a 90% CI of [19.9, 46.7]. Within each stage strata, there did not appear to be any meaningful response and survival differences by treatment arm. Conclusions: Survival is similar for both treatment arms and does not appear superior to results achieved in other trials with rigorous pretreatment staging. Neither regimen appears likely to advance treatment of esophageal/GEJ adenoca over preoperative cisplatin/5-FU/RT. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Bristol-Myers Squibb, Pfizer, sanofi-aventis Amgen, AstraZeneca Oncology, Bristol-Myers Squibb, Pfizer