Hyun Cheol Chung, MD
The investigational anti–PD-L1 antibody avelumab demonstrated clinical activity as a second-line and maintenance therapy for patients with unresectable gastric or gastroesophageal junction (GEJ) cancer, according to a report at the 2016 Gastrointestinal Cancers Symposium.
Among 55 patients who received avelumab maintenance after first-line chemotherapy in the phase Ib study, one had a complete response and three others had partial responses, for an overall response rate (ORR) of 7.3%. In the second-line setting, avelumab demonstrated an ORR of 15%. Stable disease rates were 35% in the second-line setting and 47.3% in the maintenance cohort.
“Treatment with avelumab in patients with gastric or gastroesophageal junction cancer was associated with an acceptable safety profile and showed clinical activity, including 1 complete response among patients receiving avelumab in the maintenance setting,” Hyun Cheol Chung, MD, a medical oncologist at Yonsei Cancer Center in Shinchon-Dong, South Korea, and colleagues concluded in a poster presentation.
The phase Ib trial focused on patients whose disease progressed after first-line chemotherapy (n = 20) or those who did not have disease progression during first-line therapy (n = 55). In both cohorts, avelumab was administered at 10 mg/kg every 2 weeks.
Safety and tolerability were the trial’s primary objectives. Secondary endpoints included assessment of best overall response, progression-free survival (PFS), and the association between PD-L1 expression (on tumor cells and immune cells) and subsequent clinical activity of avelumab.
Patients in the second-line and maintenance cohorts had similar baseline characteristics. The median ages were 56 and 57 years, 75% to 80% were male, and the histology was unspecified in 60% to 65% of patients in the second-line and maintenance arms, respectively.
Avelumab led to a partial response in 3 patients and stable disease in 7 others in the second-line cohort, resulting in a disease control rate of 50%. In the maintenance cohort, 4 patients had partial responses and 26 had stable disease for a disease control rate of 54.5%.
Nine patients (4 second-line, 5 maintenance) had tumor shrinkage >30%. These responses included 2 patients who had HER2-positive disease and 2 others with stable disease who did not qualify for response because of the appearance of a new lesion on subsequent scans.
At the time of the analysis, median duration of response had not yet been reached. Responses were observed in patients with PD-L1-positive and PD-L1-negative tumors. Responses occurred within 5 to 10 weeks of starting treatment in the second-line cohort and within about 5 weeks in all responding patients in the maintenance cohort. Four of seven responses were ongoing at the last data analysis, Chung reported.
The second-line cohort had a median PFS of 11.6 weeks. At 24 weeks, 19.3% of patients remained progression free and alive. The maintenance cohort had a median PFS of 14.1 weeks and a 24-week PFS rate of 34.0%. A trend toward longer PFS was observed in patients with PD-L1–positive tumors.
PD-L1 expression status was known in 12 of 20 patients in the second-line cohort and 43 of 55 in the maintenance cohort. Using a cutoff of ≥1% expression in tumor cells, five patients (41.7%) in the second-line cohort had PD-L1-positive tumors, as did 15 of those in the maintenance cohort (34.9%).
Raising the cutoff to ≥5% expression produced PD-L1-positive rates of 16.7% and 16.3% and raising the cutoff to 25% resulted in positive rates of 16.7% and 0% for the second-line and maintenance cohorts, respectively. Assessment of PD-L1 expression in tumor-infiltrating lymphocytes showed that 16.7% of patients in the second-line cohort and none of those in the maintenance group had tumors with PD-L1 expression levels ≥10%.
In patients with PD-L1 expression on ≥5% of cells, the ORR in the second-line setting was 50% (1 out of 2). In the maintenance setting (n = 7), there was 1 response, for an ORR of 14.3%. The median PFS was not reached for those in the second-line group and was 18.0 weeks in the maintenance group.
For those with ≥1% tumor expression, the ORR was 20% in the second-line setting. The ORR was 6.7% in the maintenance setting. The median PFS was 36 weeks in the second-line group and 17.6 weeks for those in the maintenance group.
With respect to safety, 47 of the 75 patients (63%) in both cohorts had treatment-emergent adverse events. The most frequently reported adverse events (all grades) were infusion-related reactions (16%), nausea (9.3%), elevated liver enzymes (9.3% each for AST and ALT), fatigue (8%), vomiting (8%), chills (8%), and pruritus (8%). The only grade 3/4 adverse event that occurred in more than one patient was fatigue (two patients, 2.7%).