TY - JOUR
T1 - Pembrolizumab Plus Chemotherapy Per PD-L1 Stratum In Patients With Metastatic Non-Small Cell Lung Cancer
T2 - Real-World Effectiveness Versus Trial Efficacy
AU - Verschueren, Marjon V
AU - Peters, Bas Jm
AU - Bloem, Lourens T
AU - Kruik, Veerle R
AU - Uitvlugt, Elien B
AU - Bijsmans, Annette R
AU - Egberts, Antoine CG
AU - van de Garde, Ewoudt Mw
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2024/3
Y1 - 2024/3
N2 - BACKGROUND: Clinical trial efficacy and real-world effectiveness of oncological treatments can differ. This study assessed the real-world survival outcomes of first-line pembrolizumab plus chemotherapy per PD-L1 stratum in patients with metastatic non-small cell lung cancer (mNSCLC) and compared them to clinical trial results.PATIENTS AND METHODS: All patients with nonsquamous and squamous mNSCLC who received first-line pembrolizumab plus chemotherapy in 7 Dutch teaching hospitals between January 1, 2019 and December 31, 2021 were included. Hazard ratios (HR) with confidence intervals (95% CI) for overall survival (OS) and progression-free survival (PFS) were estimated to determine the efficacy-effectiveness gap (EE gap) between real-world and clinical trial, stratified by PD-L1 stratum.RESULTS: The nonsquamous cohort (n = 486) consisted of 269 patients with PD-L1 < 1%, 158 with PD-L1 1% to 49%, and 59 with PD-L1 ≥ 50%. The squamous cohort (n = 117) consisted of 70 patients with PD-L1 < 1% and 47 with PD-L1 ≥ 1%. For OS, an EE gap was observed in nonsquamous patients with PD-L1 < 1% (HR 1.38 (95% CI 1.06-1.78; median OS 10 vs. 17.2 months) and HRs consistently >1 in all other nonsquamous and squamous PD-L1 strata, although not statistically significant. No EE-gap for PFS was observed in any stratum.CONCLUSION: No significant EE gap was found for pembrolizumab plus chemotherapy, except in the stratum nonsquamous mNSCLC with <1% PD-L1 tumor expression. In these patients, the survival in real-world was considerably shorter compared to the clinical trial results. Further studies are needed to determine which patient, treatment and or context factors contribute to this disparity.
AB - BACKGROUND: Clinical trial efficacy and real-world effectiveness of oncological treatments can differ. This study assessed the real-world survival outcomes of first-line pembrolizumab plus chemotherapy per PD-L1 stratum in patients with metastatic non-small cell lung cancer (mNSCLC) and compared them to clinical trial results.PATIENTS AND METHODS: All patients with nonsquamous and squamous mNSCLC who received first-line pembrolizumab plus chemotherapy in 7 Dutch teaching hospitals between January 1, 2019 and December 31, 2021 were included. Hazard ratios (HR) with confidence intervals (95% CI) for overall survival (OS) and progression-free survival (PFS) were estimated to determine the efficacy-effectiveness gap (EE gap) between real-world and clinical trial, stratified by PD-L1 stratum.RESULTS: The nonsquamous cohort (n = 486) consisted of 269 patients with PD-L1 < 1%, 158 with PD-L1 1% to 49%, and 59 with PD-L1 ≥ 50%. The squamous cohort (n = 117) consisted of 70 patients with PD-L1 < 1% and 47 with PD-L1 ≥ 1%. For OS, an EE gap was observed in nonsquamous patients with PD-L1 < 1% (HR 1.38 (95% CI 1.06-1.78; median OS 10 vs. 17.2 months) and HRs consistently >1 in all other nonsquamous and squamous PD-L1 strata, although not statistically significant. No EE-gap for PFS was observed in any stratum.CONCLUSION: No significant EE gap was found for pembrolizumab plus chemotherapy, except in the stratum nonsquamous mNSCLC with <1% PD-L1 tumor expression. In these patients, the survival in real-world was considerably shorter compared to the clinical trial results. Further studies are needed to determine which patient, treatment and or context factors contribute to this disparity.
KW - Efficacy-effectiveness gap
KW - First-line immunochemotherapy
KW - Metastatic non–small cell lung cancer
KW - PD-L1 expression
KW - Real-world versus trial
UR - http://www.scopus.com/inward/record.url?scp=85184154207&partnerID=8YFLogxK
U2 - 10.1016/j.cllc.2023.12.011
DO - 10.1016/j.cllc.2023.12.011
M3 - Article
C2 - 38246791
SN - 1525-7304
VL - 25
SP - 119-127.e1
JO - Clinical lung cancer
JF - Clinical lung cancer
IS - 2
ER -