Systematic Literature Review of Real-World Evidence on Overall Survival in Cancer Patients Before and After the Approval of Anti-PD-(L)1 Therapy

OBJECTIVES: The development and regulatory approval of anti-PD-(L)1 agents, based on positive clinical trial results, has dramatically changed oncology clinical practice and treatment paths. However, the effectiveness of anti-PD-(L)1 therapy in real-world settings is not well understood. Therefore, real-world evidence on the overall survival (OS) of cancer patients who would currently be eligible for anti-PD-(L)1 therapy but were treated with conventional care before its approval and those who received anti-PD-(L)1 therapy after its approval was identified and summarized through a systematic literature review.

METHODS: Observational studies reporting the OS of previously untreated patients with advanced/metastatic non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), or melanoma in the anti-PD-(L)1 therapy pre- and post-approval eras were identified through MEDLINE and Embase searches. Study selection and data extraction were conducted by two independent reviewers. Median OS (mOS) was descriptively summarized within each tumor type.

RESULTS: A total of 86, 42, and 35 studies evaluating first-line treatments for NSCLC, RCC, and melanoma, respectively, were included. Post-approval mOS tended to be numerically longer than pre-approval mOS within certain patient and treatment categories. For example, considering NSCLC patients, pre-approval mOS ranged from 6.9 to 18.4 months (n=18 treatment groups), and post-approval mOS ranged from 10.6 to 46.2 months in patients with PD-L1 tumor expression ≥50% who received anti-PD-(L)1 monotherapy (n=33; with mOS not reached for n=3). Considering RCC patients with poor IMDC/MSKCC risk, pre-approval mOS ranged from 2 to 10.3 months (n=7), and post-approval mOS ranged from 7.8 to 24.3 months (n=4). Also, considering melanoma patients with BRAF mutation, pre-approval mOS was 14.2 months (n=1), and post-approval mOS ranged from 15.9 to 51.2 months (n=6; with mOS not reached for n=3).

CONCLUSIONS: Real-world evidence suggests a survival benefit associated with the approval of anti-PD-(L)1 therapy for first-line populations of advanced/metastatic cancer patients.