Evaluating First-line Dostarlimab Versus Pembrolizumab With Chemotherapy in mNSCLC

In patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), dostarlimab and pembrolizumab, in combination with chemotherapy, demonstrated similar clinical efficacy as a first-line therapy, according to results of the phase 2 PERLA trial. The findings were published in Nature Communications.

The global, double-blind, parallel PERLA trial investigated the efficacy and safety of anti–PD-1 antibodies dostarlimab and pembrolizumab in conjunction with chemotherapy in previously untreated metastatic nonsquamous NSCLC without known targetable genomic aberrations. Patients were stratified by their PD-L1 tumor proportion score and smoking status, then randomized 1:1 to dostarlimab plus chemotherapy (DCT) or pembrolizumab plus chemotherapy (PCT).

The DCT cohort received ≤35 cycles dostarlimab, 500 mg, every 3 weeks, and the PCT group received ≤35 cycles of pembrolizumab, 200 mg, also every 3 weeks. The chemotherapy regimen was ≤35 cycles of pemetrexed, 500 mg/m², and ≤4 cycles cisplatin (75 mg/m²) or carboplatin (AUC 5 mg/ml/min), every 3 weeks. The primary outcome was overall response rate (ORR), and secondary outcomes were progression-free survival (PFS), overall survival (OS), and safety.

In total, 243 patients were enrolled from November 19, 2020, to February 18, 2022. The trial is active but no longer recruiting, and the published study shows results from the data cutoff of July 7, 2022.

At data cutoff, patients in the DCT group had received a mean of 15 cycles with a duration of exposure of 8.97 months. In the PCT group, the mean number of cycles was 11.3, with a median duration of 5.63 months. The ORR for DCT was 45% (55 of 121 patients; 95% CI, 36%-55%); 4 patients had a complete response (3%) and 51 had a partial response (42%). The ORR in the PCT group was 39% (48 of 122 patients; 95% CI, 31-49%), with 6 complete responses (5%) and 42 partial responses (34%).

Median PFS was 8.8 months in the DCT group (95% CI, 6.7-10.4) and 6.7 months in the PCT group (95% CI, 4.9-7.1). The hazard ratio (HR) for PFS in the DCT versus PCT groups was 0.70 (95% CI, 0.5-0.98). In the DCT group, median OS was 19.4 months (95% CI, 14.5-not reached), compared with 15.9 months in the PCT group (95% CI, 11.6-19.3). The HR for OS in the DCT versus PCT groups was 0.75 (95% CI, 0.53-1.05). The 12-month OS rate was 63% in the DCT group and 58% in the PCT group. Overall safety profiles were similar between treatment arms. The most frequent treatment-related adverse events in the DCT and PCT groups were anemia (41% and 39%, respectively), diarrhea (35% and 38%), asthenia (21% and 23%), nausea (both 20%), and neutropenia (15% and 18%).

“Overall, the antitumor activity of dostarlimab plus chemotherapy in PERLA is in line with previously published data on other [first-line] PD-1 inhibitor-chemotherapy combinations in similar nonsquamous NSCLC patient populations,” the authors summarized. “The current findings support the hypotheses that dostarlimab plus chemotherapy is effective and tolerable in patients with metastatic nonsquamous NSCLC, and that dostarlimab is a suitable PD-1 inhibitor backbone for future combinations under investigation.”