Phase II study of neoadjuvant NALIRIFOX followed by chemoradiation with paclitaxel and carboplatin in locally advanced gastroesophageal cancer.

• DOI: 10.1200/jco.2025.43.4_suppl.452
• Publication Date: 2025-01-27T14:35:52Z
• Authors: Jennifer Yon-Li Wo; Matthew Strickland; Beow Y. Yeap; Zoe Guan; Florence Keane; Hannah Johnson Ro...; Christopher Morse; Michael Lanuti; John Thomas Mullen; Uma Sachdeva; Hugh G. Auchincloss; Bailey Mendel; Lorraine C. Drapek; Jessica Meurer; Lawrence Scott Bl...; jeffrey William c...; Theodore S. Hong; Samuel J. Klempner
• Keywords: Carboplatin; Chemoradiotherapy; Neoadjuvant Therapy

452 Background: We performed a single-arm phase II study of neoadjuvant NALIRIFOX and chemoradiation (CRT) with concurrent carboplatin/taxol (C/T) followed by surgery in patients locally advanced gastroesophageal (GE) cancer. Methods: Patients were enrolled on an NCI sponsored, prospective, single arm (NCT04656041). Key eligibility criteria included: histologically confirmed T3/4 or lymph node (LN) positive GE junction esophageal cancer, ECOG PS ≤1, age 18+, life expectancy > 3 months. Exclusion metastatic disease, prior chemotherapy RT, targeted therapy for diagnosis. Extensive LN disease beyond the surgical field (supraclavicular para-aortic) was permitted if deemed feasible to be encompassed within RT field. Laparoscopy not required. Pts treated x 4-8 cycles pending patient tolerance physician discretion, restaging, CRT (50.4 Gy 28 fractions) C/T, resection. Dose reductions at discretion treating physician. The primary endpoint pathologic complete response rate following treatment C/T. Major (mPR) defined as Tumor Regression Grade 0 1. Secondary endpoints 1) acute toxicity; 2) clinical per RECIST criteria; 3) PFS 4) OS. Results: From June 2021 October 2023, 40 enrolled. Median 64 (range: 47-82), 31 male (78%). All started NALIRIFOX, median number received 5 1-8). Reasons discontinuation were: (n=29), subject withdrew from (n=2), progressive (n=1), death (n=1). Rates grade 3+ toxicity overall, gastrointestinal, hematologic attributed 55%, 35%, 13% respectively. 35 chemoRT (88%) 33 completed (83%). 86%, 11%, 9% Of who chemoRT, two declined (including 1 CR), (78%) went exploration. No found intraoperative metastases. Therefore, underwent In total, 9 had pCR (29% resected cohort, 23% ITT cohort) 15 major PR (48% 38% cohort). 10 (25% ITT) clinically CR year. Conclusions: Neoadjuvant is acceptable rates completion toxicity. our trial, promising further studies incorporating this regimen should considered. Clinical trial information: NCT04656041 .