4499 - Association of PD-L1 expression with prognosis among patients with 10 select cancers

Background

In the phase 2 KEYNOTE-158 trial (NCT02628067), pembrolizumab demonstrated enhanced activity across multiple tumor types that were PD-L1-positive or microsatellite instability-high (MSI-H). The prognostic effect of these biomarkers across cancers treated with standard of care (SOC) therapy is uncertain. This study investigated PD-L1-positive and MSI-H prevalence and associations with clinical outcomes among patients (pts) who received SOC for the tumor types included in KEYNOTE-158.

Methods

This retrospective observational study evaluated PD-L1 expression and MSI status across 10 advanced solid tumors (anal, biliary, endometrial, cervical, vulvar, thyroid, and salivary gland cancers, small-cell lung cancer, neuroendocrine tumors, and mesothelioma). Archived tumor tissue blocks (FFPE) obtained from 40–45 pts per tumor type (samples identified via a pathology network and representative of pts with cancer in Denmark) were freshly cut and centrally evaluated for PD-L1 expression using the PD-L1 IHC 22C3 pharmDx (Agilent Technologies, Carpinteria, CA) and for MSI using PCR and/or IHC. Samples with PD-L1 combined positive score (CPS) ≥1 were considered positive. OS was analyzed by biomarker status using the Kaplan-Meier method and log-rank test. Cox model HRs were adjusted for age, gender, sample year, and ECOG PS.

Results

Among 404 eligible pts (63% female) with available samples and clinical data, median age was 66 [IQR, 64–67] years and most had ECOG PS of 0 (37%) or 1 (22%). Of 398 samples evaluable for PD-L1 expression (99% of pts), 61% (95% CI, 56–66) were positive. Overall, OS following first-line treatment after index diagnosis was shorter among pts with PD-L1-positive (median 23.0 mo [95% CI, 18.1–37.1]) vs PD-L1–negative tumors (median 39.7 mo [95% CI, 23.7–73.5]; P = 0.01; adjusted HR 1.46 [95% CI, 1.11–1.92]). OS after second-line treatment (PD-L1-negative, n = 33; PD-L1-positive, n = 58) did not differ significantly by PD-L1 status (P = 0.77). Among 360 samples evaluable for MSI (89% of pts), only 8 (2%) were positive.

Conclusions

PD-L1 was commonly expressed across the 10 cancers evaluated and was associated with worse prognosis for pts who received SOC. MSI-H prevalence was very low in this population.

Clinical trial identification

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Editorial Acknowledgement

Medical writing and editorial assistance was provided by Sheri Arndt, PharmD, of C4 MedSolutions, LLC (Yardley, PA), a CHC Group company. This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

T. Steiniche: Research funding, travel, accommodation, expenses: MSD. M. Ladekarl: Travel, accommodation, other expenses: Celgene, Bayer. S. Andreasen: Stock or other ownership interest: Novo Nordisk. M. Busch-Sørensen: Employment and stock or other ownership interest: MSD Denmark. W. Zhou, K-L. Liaw: Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. S.K. Pruitt, A.K. Joe: Employment, stock or other ownership interest: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. All other authors have declared no conflicts of interest.