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

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.

• Authors: Miaomiao Gou, Yong Zhang, Zhikuan Wang, Niansong Qian, Guanghai Dai
• Journal: Investigational new drugs (Invest New Drugs) Vol. 42 Issue 2 Pg. 171-178 (Apr 2024) ISSN: 1573-0646 [Electronic] United States
• PMID: 38347177 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: © 2024. The Author(s).

Chemical References

• Paclitaxel
• Immune Checkpoint Inhibitors
• apatinib
• B7-H1 Antigen
• Albumins
• Pyridines

Topics

• Humans
• Paclitaxel (adverse effects)
• Immune Checkpoint Inhibitors (therapeutic use)
• Stomach Neoplasms (drug therapy, etiology)
• B7-H1 Antigen
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Albumins (therapeutic use)
• Pyridines