Immunochemotherapy regimen shows ‘encouraging’ results in advanced gastric cancer
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Key takeaways:
- Researchers noted the combination achieved the trial’s primary endpoint of a pathologic complete response rate.
- Median disease-free survival and OS had not been reached.
A regimen of pembrolizumab plus chemotherapy given before and after surgery induced a pathologic objective response in approximately 60% of patients with advanced gastric cancers, phase 2 study results published in JAMA Oncology showed.
The regimen appeared well tolerated among the patients with resectable metastatic gastric and gastroesophageal junction adenocarcinoma, according to researchers.
“Despite perioperative chemotherapy, a majority of patients with gastric/[gastroesophageal junction] tumors who undergo an attempt at curative resection experience disease recurrence,” Gulam Abbas Manji, MD, PhD, associate professor of medicine in the division of hematology and oncology at Columbia University Irving Medical Center, told Healio.
“We wanted to know whether addition of immunotherapy with pembrolizumab would increase pathological complete response as a surrogate for improved recurrence-free survival,” Manji added. “This single-arm study also provided encouraging 2-year recurrence-free survival.”
Background and methodology
Combining an immune checkpoint inhibitor with chemotherapy can improve outcomes for patients with metastatic gastric and gastroesophageal junction adenocarcinoma, according to background information provide by study investigators. The current unknown, they added, is whether this combination’s can be effective if given before and after surgery.
Manji and colleagues conducted an open-label study to evaluate the safety and preliminary activity of perioperative chemotherapy and immune checkpoint blockade followed by maintenance immune checkpoint blockade among patients with metastatic gastric and gastroesophageal adenocarcinoma.
The study enrolled 36 patients with resectable metastatic gastric and gastroesophageal adenocarcinoma with a median follow-up of 35.2 months (range, 17.4-73).
Study participants received three cycles of 625 mg/m2 capecitabine twice orally for 21 days, 130 mg/m2 IV oxaliplatin and 200 mg IV pembrolizumab (Keytruda, Merck), with optional 50 mg/m2 epirubicin, every 3 weeks before and after surgery. Patients also received an additional cycle of pembrolizumab before surgery and an additional 14 doses of maintenance pembrolizumab.
Of the 36 enrolled patients, researchers deemed 34 (median age, 65.5 years; 67.6% men) evaluable for efficacy analysis, with 28 patients (82.4%) undergoing curative resection.
Pathologic complete response rate served as the study’s primary endpoint, with secondary endpoints including overall response rate, DFS, OS and safety.
Results
Of the 34 evaluable patients, seven (20.6%; 95% CI, 10.1-100) achieved a pathologic complete response and six (17.6%) had a pathologic near-complete response.
Among the 28 patients who underwent resection, four (14.3%) experienced disease recurrence. Researchers noted that the median DFS and OS had not been reached by the study’s data cutoff date.
Researchers reported a 2-year DFS rate of 67.8% (95% CI, 0.53-0.87) and a 2-year OS rate of 80.6% (95% CI, 0.68-0.96).
Grade 3 or higher treatment-related adverse events occurred in 20 (57.1%) patients, with 12 (34.3%) experiencing grade 3 or higher immune-related adverse events.
Next steps
The study met its primary endpoint of pathologic complete response rate, leading the researchers to call for further development of studies that investigate potential uses for this combination in the perioperative setting for this patient population.
“This study demonstrates that providing immunotherapy in combination with chemotherapy is feasible and results in tumor downstaging,” Manji told Healio.
“There are multiple ongoing studies evaluating whether addition of immune checkpoint blockade to chemotherapy will result in an overall survival benefit. Clearly, not all patients benefit from this combination, and the question is, why,” he added. “Discovering who is more likely to benefit will be informative so that future trials are done in that biomarker-select population.”
For more information:
Gulam A. Manji, MD, PhD, can be reached at Division of Hematology and Oncology and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 161 Ft. Washington Ave., Suite 8-809, New York, NY 10032; email: gam2140@cumc.columbia.edu.
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