1440P - Neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma with camrelizumab, albumin-paclitaxel, carboplatin and apatinib (GASTO-1093): A single-arm, open-label, phase II trial.

Background

Apatinib, a selective inhibitor of VEGFR2, showed a synergistic effect when combined with camrelizumab and chemotherapy in advanced esophageal squamous cell carcinoma (ESCC). We aim to assess the efficacy and safety of using the combination of camrelizumab with apatinib and chemotherapy as the neoadjuvant therapy for ESCC.

Methods

Patients with untreated, resectable (stage II or III) ESCC were enrolled. Each patient received two 21-day cycles of neoadjuvant treatment with intravenous camrelizumab, albumin-paclitaxel, carboplatin on day 1, and oral apatinib on days 1-14, followed by the third cycle without apatinib. The primary end point was pathological complete response (PCR). Secondary endpoints included safety, objective response rate (ORR) and disease control rate (DCR).

Results

Between February 2022 and November 2023, 70 eligible patients were enrolled. Three patients discontinued the treatment due to toxicity and 67 patients have completed the full three-cycle treatment. The ORR and DCR were 89.3% and 100%, respectively. 60 (85.7%) patients underwent surgery, and R0 resection was achieved in all cases. PCR was identified in 25 (41.6%) patients, and 5 (8.3%) patients had complete response of the primary tumor but residual disease in lymph nodes alone. Grade 3 or 4 trAEs included neutropenia (57.8%), leukopenia (55.2%), thrombocytopenia (28%), hepatitis (14.2%), febrile neutropenia (12.4%), hypertension (8.6%), and rash (4.2%). The median follow-up was 18.76 months and the 1-year DFS and OS rate was 90% and 95.7%. In prespecified exploratory biomarker analysis, PCR group exhibited elevated infiltrating cytotoxic T cells and effector memory T cells compared to the non-pCR group. Increased abundance of mature tertiary lymphoid structures was associated with PCR.

Conclusions

Neoadjuvant camrelizumab combined with apatinib and chemotherapy in patients with resectable ESCC achieved a high PCR rate (41.6%) and manageable trAEs. Larger cohorts are needed to examine whether this regimen is superior to that of camrelizumab combined with chemotherapy only regarding PCR and long-term survival.

Clinical trial identification

ChiCTR2100051763.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Institutional funding of First Affiliated Hospital of SUMS.

Disclosure

All authors have declared no conflicts of interest.