Efficacy, innovativeness, clinical trials, endpoints, and price of drugs with FDA approval for non-small cell lung cancer (NSCLC)

BackgroundNovel immunotherapies and targeted therapies transformed the treatment of NSCLC. We systemically evaluated the efficacy, innovativeness, and clinical evidence underlying these drug approvals.MethodsWe identified 30 drugs with 56 FDA-approved indications for NSCLC (2000-2022). Clinical trial, approval and price data were collected from FDA labels, clinicaltrials.gov, and Medicare and Medicaid. Hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS), and relative risk (RR) for tumor response were meta-analyzed.ResultsDrugs acted via a targeted (61%), immune-regulating (32%), and cytotoxic (7%) mechanism of action. Approval was granted to small-molecules (59%) and antibodies (41%). Indications were predominantly first- (66%) or second-line (32%), for monotherapy (71%) and biomarker-based (64%). Indications were for EGFR+ (18%), ALK+ (16%), and PD-1/PD-L1+ (14%) patients. Indications utilized FDA’s special approval: orphan (46%), fast track (23%), accelerated approval (36%), priority review (80%), breakthrough therapy (50%). Approval was mostly supported by open-label (82%) phase 3 (63%) randomized-controlled (66%) trials enrolling a median of 307 patients (IQR: 158-716) for 3.1 years (IQR: 2.5-4.2). HRs were 0.76 for OS (95%CI: 0.73-0.80) and 0.66 for PFS (95%CI: 0.60-0.72), tumor response was 1.38 (95%CI: 1.27-1.49). Novel drugs increased OS by a median of 3.0 months (IQR, 1.8-4.3) and PFS by 1.8 months (IQR, 0.5-5.2). Greater OS (4.1 vs. 2.8 months, p=0.067) and PFS (5.2 vs. 1.1 months, p=0.007) benefits were observed for drugs with a biomarker. For immune-regulators, correlations between PFS/ORR with OS was 0.70/-0.97 respectively while that for targeted agents was 0.10/-0.19. Mean prices per month were $18,822 for drugs with and $12,962 (p=0.004) for those without a biomarker.ConclusionsOver the past 22 years, the approval of innovative and effective drugs transformed the landscape of NSCLC treatment. Biomarker-guided targeted therapies resulted in substantial improvements in OS and PFS. Our analysis provides a roadmap informing future drug development efforts, use of surrogate endpoints, unmet needs, and access to new NSCLC treatments.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.