Camrelizumab Combined with Chemotherapy Followed by Camrelizumab plus Apatinib as First-line Therapy for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Abstract

Purpose: Capecitabine plus oxaliplatin (CAPOX) is one of the standard first-line treatments for unresectable, advanced, or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Camrelizumab shows promising antitumor activity in advanced or metastatic G/GEJ adenocarcinoma in a phase I study. We reported the outcomes of cohort 1 in a multicenter, open-label, phase II trial, which assessed camrelizumab in combination with CAPOX followed by camrelizumab plus apatinib as a first-line combination regimen for advanced or metastatic G/GEJ adenocarcinoma. Patients and Methods: Systemic treatment-naïve patients with EGFR2-negative advanced or metastatic G/GEJ adenocarcinoma received initial camrelizumab plus CAPOX for 4–6 cycles, and patients without progressive disease were administrated subsequent camrelizumab plus apatinib. Primary endpoint was objective response rate (ORR). Results: All 48 enrolled patients comprised the efficacy and safety analysis population. The ORR was 58.3% [95% confidence interval (CI), 43.2–72.4] with this combination regimen. Median duration of response was 5.7 months (95% CI, 4.4–8.3). Median overall survival was 14.9 months (95% CI, 13.0–18.6), and median progression-free survival was 6.8 months (95% CI, 5.6–9.5), respectively. The most common grade ≥3 treatment-related adverse events (>10%) were decreased platelet count (20.8%), decreased neutrophil count (18.8%), and hypertension (14.6%). Treatment-related death occurred in 1 patient (2.1%) due to abnormal hepatic function and interstitial lung disease. Conclusions: Camrelizumab combined with CAPOX followed by camrelizumab plus apatinib demonstrated encouraging antitumor activity and manageable toxicity as first-line therapy for patients with advanced or metastatic G/GEJ adenocarcinoma.

Germline HLA-B evolutionary divergence influences the efficacy of immune checkpoint blockade therapy in gastrointestinal cancer

“…We retrospectively collected and analyzed the data of 84 metastatic GI patients treated with ICB in the Department of GI Oncology, Peking University Cancer Hospital & Institute (PUCH), between August 1, 2015, and May 24, 2019. The blood samples and tumor tissues were additionally collected from the clinical trials (NCT02825940 [ 19 ], NCT02915432 [ 20 ], NCT03167853 [ 21 ], NCT03472365 [ 22 ], NCT02872116 [ 23 ], NCT03713905 [ 24 ], NCT03736889 [ 25 ], NCT03667170 [ 26 ], and CTR20160872 [ 27 ]) and were newly analyzed. All patients met the following criteria: (1) diagnosis of metastatic gastrointestinal cancer with failed standard treatment; (2) patients received at least one cycle of PD-1/PD-L1 inhibitors; and (3) patients with eligible blood samples, tumor sample, and adequate clinical information.…”

Efficacy and Response Biomarkers of Apatinib in the Treatment of Malignancies in China: A Review

“…The findings suggested that apatinib combined with paclitaxel-based chemotherapy might be effective and tolerable in patients with chemotherapy-refractory GC (10); apatinib combined with S-1 was not superior to other chemotherapy regimens as first-line therapy for advanced GC (12); apatinib plus neoadjuvant chemotherapy followed by resection in patients with locally advanced gastric adenocarcinoma showed favorable activity and manageable safety (11); apatinib showed promising efficacy and an acceptable safety profile in patients with advanced alpha-fetoprotein-producing GC (13). According to the results of a recent clinical trial, apatinib combined with chemotherapy and PD-1 inhibitor exerted encouraging antitumor activity and manageable toxicity as first-line therapy for patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (14). In general, apatinib is currently considered a third-line or higher-line treatment option for advanced GC in China and is being continuously tested in combination therapies and various treatment scenarios for GC.…”

Clinical Complete Remission of An Advanced Gastric Adenocarcinoma After Camrelizumab Plus Chemotherapy Followed by Camrelizumab Plus Capecitabine: A Case Report

“…The overall response rate was 58.3%. The median response duration was 5.7 months, the median OS 14.9 months, and the median PFS 6.8 months (6). This is the first report of a CCR in a patient with an advanced gastric adenocarcinoma treated with camrelizumab plus chemotherapy followed by camrelizumab plus capecitabine first-line therapy.…”

“…However, the effectiveness of chemotherapy alone is limited. In patients with advanced gastric adenocarcinomas, immunotherapy combined with chemotherapy affords stronger anti-tumor activity as first-line therapy than does chemotherapy alone ( 5 , 6 ). In our present case, the patient achieved a clinical complete response (CCR) after six cycles of treatment with carrizumab plus capecitabine, and her progression-free survival (PFS) is currently 14 months on maintenance treatment with carrizumab plus capecitabine.…”