2019 ASCO Annual Meeting!
Session: Fine-Tuning Checkpoint Inhibition: Biomarkers of Response and Resistance
Type: Clinical Science Symposium
Time: Saturday June 1, 8:00 AM to 9:30 AM
Location: Hall D1
Association of STK11/LKB1 genomic alterations with lack of benefit from the addition of pembrolizumab to platinum doublet chemotherapy in non-squamous non-small cell lung cancer.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 102)
Author(s): Ferdinandos Skoulidis, Kathryn Cecilia Arbour, Matthew David Hellmann, Pradnya Dinkar Patil, Melina Elpi Marmarelis, Mark M. Awad, Joseph Christopher Murray, Jessica Hellyer, Justin F. Gainor, Anastasios Dimou, Christine M. Bestvina, Catherine A. Shu, Jonathan W. Riess, Collin Michael Blakely, Chad Victor Pecot, Laura Mezquita, Fabrizio Tabbò, Matthias Scheffler, Vassiliki Papadimitrakopoulou, John Heymach; The University of Texas MD Anderson Cancer Center, Houston, TX; Memorial Sloan Kettering Cancer Center, New York, NY; Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; Cleveland Clinic, Cleveland, OH; Brigham and Women's Hospital, Boston, PA; Massachusetts General Hospital, Cambridge, MA; Johns Hopkins Oncology, Baltimore, MD; Stanford Cancer Institute, Stanford, CA; Massachusetts General Hospital, Boston, MA; University of Colorado Cancer Center, Aurora, CO; University of Chicago, Chicago, IL; Columbia University Medical Center, New York, NY; UC Davis Comprehensive Cancer Center, Sacramento, CA; University of California San Francisco, San Francisco, CA; UNC Lineberger Cancer Ctr, Chapel Hill, NC; Medical Oncology Department, Gustave Roussy, Villejuif, France; Universita degli Studi di Torino, Torino, Italy; Lung Cancer Group Cologne, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Dept. I of Internal Medicine, Cologne, Germany
Background: Addition of pembrolizumab (P) to platinum-doublet chemotherapy [carboplatin (or cisplatin) and pemetrexed (CP)] prolongs overall survival and is a standard of care (SOC) for the 1st line treatment of metastatic EGFR/ALK wild-type (wt) non-squamous non-small cell lung cancer (mnsNSCLC). Despite widespread adoption of the CPP regimen, molecular determinants of clinical benefit from the addition of P to CP remain poorly defined. We previously identified genomic alterations in STK11/LKB1 as a major driver of primary resistance to PD-1/PD-L1 blockade in mnsNSCLC. Here, we examine the impact of STK11/LKB1 alterations on clinical outcomes with CPP chemo-immunotherapy. Methods: 497 pts with mnsNSCLC and tumor genomic profiling encompassing STK11/LKB1 from 17 academic institutions in the US and Europe were included in this study. Clinical outcomes were collected for two distinct patient cohorts: a) 377 pts treated with first-line CPP (or > 1st line following FDA-approved TKIs) that were alive for 14 days thereafter and b) 120 STK11/LKB1-mt pts that received CP prior to regulatory approval of CPP. Results: Among 377 CPP-treated pts, STK11/LKB1 genomic alterations (N = 102) were associated with significantly shorter PFS (mPFS 4.8m vs 7.2m, HR 1.5, 95% CI 1.1 to 2.0; P = 0.0063) and shorter OS (mOS 10.6m vs 16.7m, HR 1.58, 95% CI 1.09 to 2.27; P = 0.0083) compared with STK11/LKB1-wt tumors (N = 275). ORR also differed significantly between the two groups (32.6% vs 44.7%, P = 0.049). Similar results were obtained when limiting the analysis to EGFR and ALK-wt tumors (N = 333). Importantly, in pts with STK11/LKB1-mt mnsNSCLC, addition of pembrolizumab to CP did not improve PFS (mPFS 4.8m vs 4.3m, HR 1.13, 95% CI 0.83 to 1.54, P = 0.75) or OS (mOS 10.6m vs 10.3m, HR 1.03, 95% CI 0.71 to 1.49, P = 0.79) compared to CP alone. Conclusions: In mnsNSCLC, STK11/LKB1 alterations define a subgroup of pts with inferior clinical outcomes with CPP and lack of benefit from the addition of pembrolizumab to CP chemotherapy. Novel therapeutic strategies are required to establish effective antitumor immunity in STK11/LKB1-mutant NSCLC.