Abstract 20P
Background
The KEYNOTE-189(I), KEYNOTE-407(II), and Impower-133 (III) trials established pivotal treatment regimens for metastatic non-small cell lung cancer (mNSCLC) and extensive disease small-cell lung cancer (ED-SCLC). However, the applicability of these trial results to clinical practice remains uncertain due to selection differences in patient populations between prospectively controlled trials and real-world settings. This study evaluates the external validity of these treatment principles in landmark RCTs using comparable real-world data from the Baden-Württemberg Cancer Registry (BWCR), Germany.
Methods
We analyzed patients aged 18+, diagnosed 2011–2023 with mNSCLC or ED-SCLC, who received chemoimmunotherapy (CITx) or chemotherapy (CTx) protocols consistent with those in the RCTs. Patients were selected to match the baseline characteristics of those in the original phase III trials (CITx arms: IA, IIC, IIIE; CTx arms: IB, IID, IIIF). The primary endpoint was overall survival (OS), assessed using Kaplan-Meier and multivariate Cox models, adjusted for age, sex, ECOG, and PD-L1 expression.
Results
A total of 2,353 patients were included, with 782(432) in IA(B), 204(87) in IIC(D) and 412(436) in IIIE(F). The median age was 65 years (58% male). Consistent with the trials results, we observed a plateau in OS among CITx groups. In non-squamous mNSCLC, the 3-year OS was 28.2% for IA with pembrolizumab plus CTx versus 16.3% for CTx only (IB). In squamous mNSCLC, the 3-year OS was 23.8% for IIC versus 13.3% for IID. For ED-SCLC, the 18-month OS was 23.8% for atezolizumab + CTx vs. 13.6% for CTx only. These results closely mirror those of the prospective landmark RCTs. Cox analysis identified age, ECOG, and PD-L1 expression as significant prognostic factors.
Conclusions
Real-world data from the BWCR successfully replicated the outcomes of KEYNOTE-189, KEYNOTE-407, and Impower-133, confirming the external validity of these treatment principles. This highlights the potential of using real-world data from modern state-run cancer registries to bridge the gap between clinical trials and everyday oncology practice, offering valuable insights for clinicians in real-world treatment decisions.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
W.E.E. Eberhardt: Financial Interests, Personal, Advisory Board: from AstraZeneca, BMS, MSD, Pfizer, Sanofi, Daiichi Sankyo, Regeneron, Novartis, Pierre Fabre, Roche, Amgen, Lilly Deutschland, Boehringer Ingelheim.; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Pfizer, Sanofi, Daiichi Sankyo, Regeneron, Novartis, Pierre Fabre, Roche, Amgen, Lilly Deutschland, Boehringer Ingelheim and onkowissen.de; Financial Interests, Institutional, Research Grant: AstraZeneca. All other authors have declared no conflicts of interest.