Camrelizumab plus apatinib shows ‘potent antitumor activity’ in advanced small cell lung cancer
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The immune checkpoint inhibitor camrelizumab showed clinically significant activity when combined with apatinib among patients with chemosensitive and chemoresistant extensive-stage small cell lung cancer, according to phase 2 results of the randomized PASSION trial presented at the virtual American Association for Cancer Research Annual Meeting.
The combination therapy also had an acceptable safety profile, researchers noted.
“Camrelizumab plus apatinib showed potent antitumor activity in patients with chemoresistant and chemosensitive advanced-stage small cell lung cancer after receiving chemotherapy,” Jie Wang, MD, PhD, professor in the department of internal medicine at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences in Beijing, said during a presentation.
Wang noted that most patients with small cell lung cancer have advanced-stage disease at diagnosis, and nearly all patients with this diagnosis experience disease progression after receiving platinum-based doublet chemotherapy.
Camrelizumab (SHR-1210, Jiangsu Hengrui Medicine Co.) is a PD-1 inhibitor, whereas apatinib (YN968D1, Elevar Therapeutics) is an oral, small-molecule receptor tyrosine kinase inhibitor that selectively binds to and inhibits VEGFR2.
The first phase of the PASSION trial was an open-label, three parallel-cohort study to determine the efficacy and safety of camrelizumab plus apatinib among patients with advanced small cell lung cancer. Researchers randomly assigned patients in in a 1:1:1 ratio to IV camrelizumab dosed at 200 mg every 2 weeks plus oral apatinib dosed at 375 mg once daily, 5 days on/2 days off, or 7 days on/7 days off. Each cohort included six patients.
Dose tolerability and efficacy data from the first 28-day treatment cycle in phase 1 served as the basis for expanding the daily treatment cohort for phase 2. The expanded cohort included 47 patients (median age, 62 years; range 49-70; 85% men), all but one of whom had received just one previous line of therapy.
Objective response rate per RECIST version 1.1 and safety served as the primary endpoints. Data cutoff was Dec. 12.
Results of the daily treatment cohort showed an ORR of 34% (95% CI, 20.9-49.3) median PFS of 3.6 months (95% CI, 1.9-4.6) and median OS of 8.4 months (95% CI, 4.7-12.3).
Chemosensitive (n = 16) and chemoresistant (n = 31) patients — defined as those with disease relapse 90 days or more or less than 90 days after receiving platinum-based chemotherapy, respectively — had comparable ORR (37.5% vs. 32.3%), median PFS (3.6 months vs. 2.7 months) and median OS (9.6 months vs. 8 months).
Nearly three-quarters (72.9%) of all patients experienced grade 3 or greater treatment-related adverse events. The most common serious adverse events included hypertension (25.4%), hand-foot syndrome (13.6%) and decreased platelet count (13.6%).
All reported adverse events were manageable, and no treatment-related deaths occurred, according to the investigators.
Five patients (8.5%) discontinued the study regimen because of treatment-related adverse events.
“These data warrant further clinical study of camrelizumab plus apatinib in small cell lung cancer,” Wang said. – by Drew Amorosi
Reference:
Wang J, et al. Abstract CT083. Presented at: AACR Annual Meeting; April 27-28, 2020 (virtual meeting).
Disclosures: Wang reports no relevant financial disclosures. Please see the abstract for all other researchers’ relevant financial disclosures.
Perspective
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Nicholas Rohs, MD
Although the data for this trial do show some encouraging benefit, I am not sure it has truly differentiated itself from a host of unexciting second-line options for small cell lung cancer. Although an ORR of 34% is notable for second-line small cell lung cancer therapy — particularly with responses in both chemosensitive and chemotherapy-naive disease — it is difficult to interpret in a world where first-line chemoimmunotherapy combination is becoming standard of care. It’s also hard to interpret the benefit of a single-arm study without a comparator to truly see the benefit off adding VEGF targeted therapy to checkpoint inhibition in this setting. Hopefully we can see a subsequent randomized study with more translational science to see if we can predict who may most benefit from this combination therapy, particularly given the non-negligible toxicity that the addition of anti-VEGF therapy brings.
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