Results of an interim analysis of a randomized phase 2 study evaluating maintenance therapy with the programmed cell death ligand 1 (PD-L1) inhibitor, durvalumab, in patients with advanced esophageal/gastric cancer showed a 12-week progression-free rate (PFR) of 100% in patients with a combined PD-L1 proportion in tumor and immune cells of 10% or higher. The findings from this study will be presented at the 2020 Gastrointestinal Cancers Symposium held in San Francisco, California.
Optimal approaches to maintenance therapy following first-line platinum-based chemotherapy are being actively investigated in the setting of advanced esophageal/gastric cancer.
In this open-label, randomized phase 2 clinical trial (PLATFORM; ClinicalTrials.gov Identifier: NCT02678182), 183 patients with HER2-negative locally advanced or metastatic esophageal/gastric cancer who achieved a response or stable disease following first-line platinum-based chemotherapy were randomly assigned to undergo active surveillance or receive maintenance therapy with durvalumab or capecitabine.
The primary study endpoint was progression-free survival, with secondary endpoints of PFR — defined as stable disease, partial, or complete response at 12 weeks — and PFR according to PD-L1 expression status.
Of note, the adaptive design of this study allows for adjustment of the study design during the trial (eg, on-study closure of arms based on study findings, as well as the addition of new arms evaluating other novel treatments).
The median patient age was 65 years, and more than 80% of the patients were men. The primary disease site was the esophagus, the stomach, and the esophageal/gastric junction in 40%, 32%, and 28%, of patients, respectively. Most patients (92%) had metastatic disease.
At interim analysis, 12-week PFR was 51%, 52%, and 49%, in patients undergoing surveillance or receiving capecitabine or durvalumab, respectively.
For patients receiving maintenance capecitabine, the PFR evaluated according to PD-L1 status was 53% and 43% in patients with a combined PD-L1 proportion in tumor and immune cells of less than 10% and 10% or higher, respectively. In contrast, the corresponding PFRs were 51% and 100% in patients with a combined PD-L1 proportion in tumor and immune cells of less than 10% and 10% or higher, respectively, receiving maintenance durvalumab.
This continues to be an ongoing study, as prespecified criteria for futility were not met.
Additional maintenance therapy arms evaluating the poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitor, rucaparib, as well as the combination of capecitabine plus the anti-vascular epithelial growth factor receptor 2 (VEGFR2) antibody, ramucirumab, have been added to the study. Other biomarkers being evaluated include tumor mutational burden and microsatellite instability status.
Disclosure: Some of the authors of the study disclosed financial relationships with pharmaceutical or medical device companies. For a full list of disclosures, please refer to the study abstract.
Cunningham D, Fong CYK, Peckitt C, et al. Evaluating maintenance therapies in advanced osophago-gastric adenocarcinoma (OGA): Interim analysis and biomarker results from the PLATFORM study. J Clin Oncol. 2020;38(suppl 4):Abstract 282.
This article originally appeared on Cancer Therapy Advisor