PD-1 inhibitor combined with albumin paclitaxel and apatinib as second-line treatment for patients with metastatic gastric cancer: a single-center, single-arm, phase II study

Abstract

Summary Background Immune checkpoint inhibitors have been approved for first- and third-line treatment of advanced gastric cancer. However, pembrolizumab alone in the second line did not improve overall survival compared to chemotherapy in the KEYNOTE-061 study. In this study, we aimed to explore the efficacy and safety of a three-drug regimen of PD-1 inhibitor combined with albumin paclitaxel and apatinib (a VEGFR inhibitor) for the second-line treatment of patients with metastatic gastric cancer (mGC). Methods This was a single-center, single-arm, phase II clinical study. Patients with mGC with stable microsatellite and negative HER-2 expression who failed first-line chemotherapy were enrolled. The enrolled patients were treated with PD-1 inhibitor (selected according to patients’ requirements) in combination with albumin paclitaxel (125 mg/m2, intravenously, days 1 and 8, or 250 mg/m2, intravenously, day 1) and apatinib (250 or 500 mg, orally, days 1–21) every 3 weeks. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response, and adverse events (AEs). Results From July 11, 2019, to October 13, 2022, a total of 43 patients were enrolled, of whom 10 were PD-L1 negative, 11 were PD-L1 positive, and 22 had unknown PD-L1 expression. As of the data cutoff on April 1st, 2023, nine patients had partial response, 29 had stable disease, and five experienced progressive disease, with the ORR of 20.9% and DCR of 88.3%. The median PFS was 6.2 months (95% CI, 3.9–9.3), and the median OS was 10.1 months (95% CI, 7.5–14.1). All patients suffered from alopecia and neurotoxicity. The other main AEs of grade 1 or 2 were bone marrow suppression (N = 21, 48.8%), hand-foot reaction (N = 19, 44.2%), hypertension (N = 18, 41.9%), hypothyroidism (N = 11, 25.6%), gastrointestinal bleeding (N = 3, 7.0%), and liver function damage (N = 5, 11.6%). Two patients reported grade 3–4 immune-related liver damage. Conclusion Second-line PD-1 inhibitor combined with albumin paclitaxel and apatinib showed certain efficacy and safety in patients with mGC. Trial registration Clinical trials, NCT04182724. Registered 27 November 2019; retrospectively registered, https://clinicaltrials.gov/study/NCT04182724

Prognosis and Treatment of Gastric Cancer: A 2024 Update

“…New therapeutic options are emerging every year, as in the case of advanced PD-L1-positive GC patients with extensive peritoneal metastases, where the combination of nivolumab plus modified oxaliplatin (L-OHP) with l-leucovorin (l-LV) and a bolus or continuous infusion of 5-fluorouracil (5-FU) (mFOLFOX6) has been proven to be safe and have moderate effectiveness [50]. In patients with metastatic GC, the second-line therapy, programmed cell death protein 1 (PD-1) inhibitor (selected according to patients' requirements) in combination with albumin paclitaxel (125 mg/m 2 , intravenously, days 1 and 8, or 250 mg/m 2 , intravenously, day 1) and apatinib (250 or 500 mg, orally, days 1-21) every 3 weeks, has demonstrated modest efficacy and safety [51]. Chemotherapy plus a cell division control protein 42 (Cdc42) inhibitor has demonstrated encouraging antitumor effectiveness in patients with resistant GC HER2+, offering valuable information for developing treatment plans for patients with trastuzumab-resistant GC [52].…”