The efficacy and safety of neoadjuvant camrelizumab and chemotherapy for locally advanced thoracic esophageal squamous cell carcinoma.

Abstract

278 Background: To explore the efficacy and safety of neoadjuvant camrelizumab and chemotherapy for locally advanced thoracic esophageal squamous cell carcinoma (ESCC) by an open label, single-arm, phase 2 clinical trial (ClinicalTrials.gov, Identifier number: NCT04506138). Methods: The eligible patients were arranged to receive 2 cycles of camrelizumab (200mg, day 1) combined with carboplatin (AUC = 5, day 1) and albumin paclitaxel (100 mg/m2, day 1, 8). All treatments were given intravenously in 3-week cycle. Patients underwent surgery within 4-6 weeks after the completion of neoadjuvant treatment. The primary endpoint was pathologic complete response (pCR), and secondary endpoints were major pathological response (MPR), safety and feasibility. The quality of life (QoL) was assessed by the Functional Assessment of Cancer Therapy-Esophageal (FACT-E) scale and EQ-5D-3L scale. Results: A total of 46 patients were recruited, among whom the clinical stage II, III, and IVa at baseline were 11 (23.9%), 33 (71.7%), and 2 (4.3%), respectively. Forty-five patients completed 2 cycles of neoadjuvant treatment. One patient received 1 cycle of neoadjuvant treatment and then lost to be followed up. Eight patients did not receive surgery. Except 1 patient accept exploratory surgery, 37 patients (37/46, 80.4%) achieved R0 resection. Eight patients (8/37, 21.6%) had pCR in both primary tumors and lymph nodes. MPR of primary tumors and lymph nodes was observed in 18 patients (18/37, 48.6%). During neoadjuvant treatment period, all 46 patients presented with treatment-related AEs (TRAEs) of any grade. Seven patients (7/46,15.2%) experienced grade ≥ 3 TRAEs. One patient suffered grade 5 immune-associated pneumonia. The most common TRAEs were anemia (32/46, 70.0%), followed by thrombocytopenia (15, 32.6%), leukopenia (14, 30.4%), neutropenia (13, 28.3%), rash (12, 26.1%), reactive cutaneous capillary endothelial proliferation (RCCEP) (7, 15.2%). The median interval between the first cycle of neoadjuvant treatment and surgery was 64 days (range, 56-77 days). Symptom scores in FACT-E scale were improved by neoadjuvant treatment (t = -2.60, P = 0.01). PD-L1 CPS (< 10 vs ≥ 10), PD-L1 TPS (< 1% vs ≥ 1%) and TMB (split according to top 20% of TMB value) had no effect on the pCR rate and MPR rate. Conclusions: Neoadjuvant camrelizumab combined with chemotherapy achieved a promising pathologic response, which was effective and safe. Meanwhile, neoadjuvant treatment improved QoL of patients. Some larger multi-center trials are undergoing for further confirmation of efficacy and safety. Clinical trial information: NCT04506138.

Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced esophageal cancer: A meta-analysis

“…As the heterogeneity was significant ( p < 0.001, I 2 = 83%), a random-effects model would have been appropriate. Grade 3–5 TRAEs comprised a single case of death due to pneumonia and acute respiratory failure ( 23 ) and a solitary case of death due to immune-related pneumonia ( 30 ). The others were mainly manageable adverse events such as myelosuppression, leukopenia, neutropenia, anemia, fatigue, and thrombocytopenia, which did not contribute to serious adverse outcomes or result in higher postsurgical rates of mortality.…”

“…In the end, 21 studies, which included 759 patients, were used for the analysis. Of the 21 studies included, there were 20 single-arm open-label cohort studies (15,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37) and there was one two-arm open-label randomized controlled trial (RCT) (38). Of the 21 studies included, three are still ongoing (26,29,30) and 18 (15, 19-25, 27, 28, 31-38) have been completed.…”

“…Of the 21 studies included, there were 20 single-arm open-label cohort studies (15,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37) and there was one two-arm open-label randomized controlled trial (RCT) (38). Of the 21 studies included, three are still ongoing (26,29,30) and 18 (15, 19-25, 27, 28, 31-38) have been completed. The main neoadjuvant immunotherapy drugs include pembrolizumab, sintilimab, and camrelizumab, amongst others.…”

“…In our meta-analysis, the mean incidence of grade ≥3 TRAEs was 16.3%, which demonstrated good tolerability and was lower than the incidence of ≥ grade 3 TRAEs (39.5%) in neoadjuvant chemotherapy in the ESCORT study ( 46 ). The mortality rate of TRAEs is low, with only two deaths ( 23 , 30 ) associated with the pneumonia-related disease. In addition, a majority of ICIs had been previously assessed in complete preliminary clinical studies and had been used in the treatment of a variety of advanced tumors and therefore there is extensive experience in the identification and treatment of adverse events.…”

“…A total of 759 patients were enrolled in the study, 38 (24) of whom received one cycle of neoadjuvant immunotherapy combined with chemotherapy, the remaining patients received two to four cycles of neoadjuvant immunotherapy combined with chemotherapy, 677 patients underwent follow-up surgery, and 18 (26,29,30) patients awaited surgery. R0 resection was achieved by 664 (15,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38) patients.…”