Camrelizumab–apatinib has antitumor activity in previously treated SCLC patients
medwireNews: Phase 2 PASSION trial data point to the potential of camrelizumab plus apatinib for the second-line treatment of extensive-stage small-cell lung cancer (ES-SCLC).
Presenting the findings at the 2020 AACR Virtual Annual Meeting I, researcher Jie Wang (Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing) explained that “nearly all [ES-SCLC] patients progress after first-line treatment with platinum–etoposide doublet” and outcomes with second-line topotecan are poor.
They therefore investigated the combination of the PD-1 inhibitor camrelizumab and the VEGFR2 tyrosine kinase inhibitor apatinib as a potential second-line option for these patients.
In the first stage of the trial, patients were assigned to receive camrelizumab 200 mg every 2 weeks alongside three different schedules of apatinib 375 mg/day, namely, continuous dosing (n=6), 5 days on followed by 2 days off (n=6), and 7 days on followed by 7 days off (n=6).
Wang reported that based on the tolerability and efficacy during the initial 28 days, the continuous dosing regimen was selected for the expansion cohort, which enrolled a further 41 participants.
In this cohort of 47 patients in total, the objective response rate (ORR) was 34.0%, with similar rates for the 16 chemotherapy-sensitive (relapse ≥90 days after chemotherapy) and the 31 chemotherapy-resistant (relapse <90 days) patients, at 37.5% and 32.3%, respectively. The corresponding disease control rates were 68.1%, 75.0%, and 64.5%.
The median progression-free survival (PFS) was 3.6 months in the expansion cohort, with durations of 3.6 and 2.7 months for the chemotherapy-sensitive and resistant patients, respectively. The median overall survival durations were a corresponding 8.4, 9.6, and 8.0 months.
Describing the safety profile as “tolerable,” Wang reported that treatment-related adverse events (TRAEs) of at least grade 3 occurred in 72.9% of the 59 patients enrolled across all dosing regimens of the trial. Hypertension was the most common event of this severity, at 25.4%, followed by platelet count decrease and hand–foot syndrome, each at 13.6%.
A total of 8.5% of participants discontinued treatment due to TRAEs, but no deaths were deemed related to the study drugs.
Wang therefore concluded that these “phase 2 data warrant further clinical studies of camrelizumab plus apatinib in SCLC.”
Discussant Ferdinandos Skoulidis (The University of Texas MD Anderson Cancer Center, Houston, USA) remarked that “the data provide preliminary evidence of antitumor activity for the combination” in patients with ES-SCLC.
He noted, however, that outcomes differed significantly by smoking status, with corresponding ORRs of 69.2% and 23.9% for never and ever smokers, for instance.
Therefore, “precise estimates of efficacy [of the combination] are confounded by a high proportion of never smokers” in the trial, and “the clinical efficacy in smokers needs to be further defined,” concluded Skoulidis.
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