This indirect comparison and meta-analysis was conducted to comprehensively compare the therapeutic effects of PD-1/L1 antibodies, chemotherapy or their combination as first-line treatments for NSCLC.
RCTs that compared the efficacy of first-line PD-1/L1 inhibitors (I) with chemotherapy (C), or with their combination (I+C) for NSCLC patients were comprehensively searched. HR of PFS and OS and their 95% CI were pooled. Subgroup analyses were conducted according to different PD-L1 expression. Traditional meta-analyses were conducted to compare the efficacy of I vs. C, or I+C vs. C. Indirect treatment comparisons (ITCs) were then conducted to compare I+C and I.
A total of 9 studies involving 6,056 patients were included. The combined ORRs of I, C and I+C were 32.0%, 31.0% and 50.6%. The combined 9m-PFS rate were 37.9%, 26.6% and 43.3%, and 2y-OS rate were 39.0%, 34.2% and 47.0% in I, C and I+C arm. Overall, I showed no significant difference with C either according to PFS (HR 0.90, 0.65-1.24) or OS (HR 0.84, 0.64-1.09), while I+C was significantly superior to C both in PFS (HR 0.63, 0.56-0.71) and OS (HR 0.68, 0.53-0.88). In indirect comparison, I+C showed advantages than I in PFS (HR 0.70, 0.50-0.99) but not OS (HR 0.81, 0.56-1.16). In PD-L1≥50% population, I had better OS than C (HR 0.71, 0.59-0.86), and I+C also had better OS than C (HR 0.57, 0.44-0.73). In indirect analysis, I+C was superior to I in terms of PFS (HR 0.50, 0.32-0.77), but not OS (HR 0.8, 0.58 to 1.10). In PD-L1 positive subgroup, I was similar with C regarding OS (HR 0.92, 0.70-1.22) and PFS (HR 1.09, 0.98-1.21), but I+C had longer PFS in this population than I (HR 0.47, 0.38 to 0.58). In PD-L1 negative subgroup, adding I to C was significantly beneficial both in OS (HR 0.76, 0.64-0.91) and PFS (HR 0.76, 0.67-0.86).
Single agent PD-1/L1 inhibitor was preferable only in PD-L1 high expression population but remained optional in all PD-L1 positive patients. Adding chemotherapy to PD-1/L1 inhibitors provided additional benefit not only in low but also in high PD-L1 expression patients. PD-1/L1 inhibitors plus chemotherapy was better than chemotherapy alone in PD-L1 negative patients. In all, we suggest combination regimen as first-line treatment for NSCLC regardless of PD-L1 expression.
Clinical trial identification
Legal entity responsible for the study
The First Affiliated Hospital of Guangzhou Medical University.
Has not received any funding.
All authors have declared no conflicts of interest.