Impact on overall survival after adjusting for treatment crossover in first-line metastatic NSCLC trials for pembrolizumab plus chemotherapy.

8596 Background: High crossover rates were observed in the chemotherapy alone arm in KEYNOTE(KN)-189 and KEYNOTE-407, attributable to protocol-permitted crossover to pembrolizumab monotherapy and subsequent anti-PD1/PD-L1 therapies per clinical practice. The objective was to assess the impact on overall survival (OS) by adjusting for treatment crossover. Methods: The analysis used pooled data from KN-189 global (NCT02578680; cut-off date: 08MAR2022) and Japan extension (NCT03950674; cut-off date: 07FEB2023), and pooled data from KN-407 global (NCT02775435; cut-off date: 23FEB2022) and China extension (NCT03875092; cut-off date: 10FEB2023). The survival time of participants (pts) in the chemotherapy alone arm who crossed over to pembrolizumab or subsequent anti-PD1/PD-L1 therapy was adjusted using a Two-Stage Estimation model (TSE) and Rank-Preserving Structural Failure Time model (RPSFT). Subsequently, a stratified Cox regression model was used to estimate the treatment effect of pembrolizumab+chemotherapy (P+C) relative to chemotherapy. Results: Overall, 646 and 669 patients were included in the analysis for KN-189 NCT03950674 ; NCT02775435 ; NCT03875092 . KN-189 KN-407 Population N Unadjusted ITT TSE RPSFT N Unadjusted ITT TSE RPSFT All comers 431 vs 215 0.60 (0.50; 0.72) 0.44 (0.33, 0.58) 0.46 (0.35, 0.61) 332 vs 337 0.65 (0.55, 0.76) 0.47 (0.35, 0.63) 0.52 (0.40, 0.67) TPS <1% 140 vs 66 0.51 (0.37, 0.70) 0.41 (0.27, 0.63) 0.42 (0.28, 0.63) 115 vs 121 0.75 (0.56, 0.99) 0.59 (0.35, 0.98) 0.64 (0.42, 0.98) TPS ≥1% 267 vs 132 0.65 (0.52, 0.82) 0.48 (0.32, 0.71) 0.50 (0.34, 0.73) 207 vs 209 0.60 (0.48, 0.74) 0.40 (0.28, 0.59) 0.45 (0.32, 0.63) TPS 1-49% 132 vs 61 0.66 (0.47, 0.92) 0.48 (0.27, 0.86) 0.54 (0.33, 0.88) 114 vs 124 0.59 (0.45, 0.79) 0.38 (0.22, 0.64) 0.45 (0.30, 0.70) TPS ≥ 50% 135 vs 71 0.66 (0.47, 0.93) <jats:td colspan="1" rowspa