Impact of Real-World Response to First-Line Immunotherapy and Chemotherapy on Subsequent Treatment Outcomes in Patients With Advanced or Metastatic Non–Small Cell Lung Cancer

PURPOSE This study examined real-world overall survival (rwOS) in patients with advanced or metastatic non–small cell lung cancer (a/mNSCLC) treated with combination immunotherapy (IO) and platinum chemotherapy in first line (1L), followed by second-line or beyond (2L+) non-IO, nonplatinum chemotherapy and explored the association between real-world duration of response (rwDOR) to 1L treatment and rwOS on the 2L+ treatment. METHODS This study used two US-based data sets: ConcertAI Patient360 NSCLC data set (ConcertAI) and the Flatiron Health Research Database (FHRD), and included adults with a/mNSCLC diagnosed from January 1, 2018, to March 31, 2023 (data cutoff: March 31, 2024). Kaplan-Meier and multivariate Cox regression analyses estimated rwOS for the index regimen by rwDOR to 1L. RESULTS Patients with rwDOR ≤6 (≈60%) v >6 months (≈40%) in 1L were similar across the 596 ConcertAI patients and 1,094 FHRD patients. Across the ConcertAI data set/FHRD, 52.6%/55.7% of patients achieved complete/partial response as real-world best overall response to 1L combination IO and platinum chemotherapy and 17.8%/19.1% had stable disease. The median rwOS on 2L+ treatment was 8.3 v 5.2 months ( P = .001; ConcertAI) and 8.3 v 5.1 months ( P < .001; FHRD) for patients with 1L rwDOR >6 v ≤6 months. The adjusted hazard ratio for patients with 1L rwDOR >6 v ≤6 months was 0.74 (95% CI, 0.61 to 0.90; P = .002) and 0.76 (95% CI, 0.67 to 0.88; P < .001) in the ConcertAI data set and FHRD, respectively. CONCLUSION Our findings demonstrate that patients with rwDOR ≥6 months on 1L combination IO and platinum chemotherapy exhibit longer rwOS on subsequent treatments. This emphasizes the need for 1L treatments that extend DOR and delay the onset of acquired resistance, which remains an unmet need for approximately 60% of patients who do not achieve a sustained response in clinical practice.