A phase II study of neoadjuvant immunotherapy combined with chemotherapy (camrelizumab plus albumin paclitaxel and carboplatin) in resectable thoracic esophageal squamous cell cancer (NICE study): Interim results.

Abstract

4060 Background: We conducted a phase II trial of preoperative chemotherapy with albumin paclitaxel and carboplatin combined with camrelizumab (NICE regimen), in patients with locally advanced esophageal squamous cell carcinoma (ESCC) with multiple lymph nodes metastasis. Initial results were analyzed to assess the efficacy and safety of this strategy. Methods: This was a prospective, multicenter, open, single arm, phase II trial. Eligible patients were histologically confirmed thoracic ESCC, staged as T1b-4a, N2-3 (≥ 3 stations), and M0 or M1 lymph node metastasis (confined to the supraclavicular lymph nodes) according to the 8th edition of American Joint Committee on Cancer. Patients received neoadjuvant treatment (NICE regimen) with intravenous camrelizumab (200 mg, day 1) plus albumin paclitaxel (100 mg/m2, day 1, 8, 15) and carboplatin (area under curve 5, day 1) of each 21-day cycle, for two cycles before surgery. The primary endpoint is pathological complete response (pCR) rate in the per-protocol population, which included all patients who had tumor resection and received at least one cycle of neoadjuvant treatment. Secondary endpoints include R0 resection rate, adverse events and disease-free survival. Safety was assessed in the modified intention-to-treat population. Results: Of the planned 60 patients enrolled, 55 (91.7%) patients have received the full two-cycles NICE regimen successfully, 4 patients didn’t receive the complete neoadjuvant therapy due to intolerance (3 patients) and drop out (1 patient), 1 patient died due to pneumonia on the second cycle of neoadjuvant therapy. Grade 3-5 treatment-related adverse events (TRAEs) rate was 53.3% and TRAEs resulting in discontinuation rate was 6.7%. The common grade 3-5 TRAEs included lymphopenia (50%), thrombocytopenia (10%), pneumonia (5%) and thyroid dysfunction (3.3%). At the time of writing, 47 patients underwent surgery within 27-85 days (median 36 days) after NICE treatment, in which 7 patients had delays to surgery due to TRAEs. All patients achieved radical (R0) resection. There was no in-hospital and postoperative 30-day mortality. pCR (ypT0N0) was identified in 20 (42.5%) of 47 patients and 5 (10.6%) patients had complete pathological response of the primary tumor but residual disease in lymph nodes alone (ypT0N+). Conclusions: Preoperative NICE regimen has achieved satisfatory initial results of disease response in locally advanced thoracic ESCC. A phase III randomized controlled trial is required to demonstarate the possible survival improvement. Trial registration: ChiCTR1900026240 Clinical trial information: ChiCTR1900026240.