2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Poster Session
Time: Sunday June 2, 8:00 AM to 11:00 AM
Location: Hall A
Randomized multicenter phase II trial evaluating the sequencing of PD-1 inhibition with pembrolizumab (P) and standard platinum-based chemotherapy (C) in patients (pts) with metastatic non-small cell lung cancer (NSCLC) (AFT-09).
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #411)
J Clin Oncol 37, 2019 (suppl; abstr 9088)
Author(s): Thomas A. Hensing, Xiaofei F. Wang, Junheng Gao, Tom Stinchcombe, Michael V. Knopp, Arkadiusz Z. Dudek, Stephen L. Graziano, Jyoti D. Patel, Bryan Faller, Konstantin H. Dragnev, David E. Kozono, Everett E. Vokes; NorthShore University Health System/University of Chicago, Evanston, IL; Duke University Medical Center, Durham, NC; Duke University Health System, Durham, NC; Duke Cancer Institute, Durham, NC; Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH; Health Partners Cancer Care Center, St. Paul, MN; Regional Oncology Center, Syracuse, NY; The University of Chicago Medical Center, Chicago, IL; Missouri Baptist Medical Center, St Louis, MO; Dartmouth-Hitchcock Medical Center, Lebanon, NH; Dana-Farber Cancer Institute, Boston, MA; Section of Hematology/Oncology, Department of Medicine, The University of Chicago Medicine, Chicago, IL
Background: KEYNOTE-024 established single-agent P as a 1st-line option for pts with metastatic NSCLC without targetable alterations and PD-L1 tumor proportion score (TPS) ≥ 50%. KEYNOTE-189 and 407 established concurrent C + P as a treatment option irrespective of PD-L1 expression. In this randomized phase II selection trial, we explored sequencing of C and P in this pt. population. Methods: Eligible pts were randomized 1:1 to (arm A) C (carboplatin (AUC 6) + pemetrexed 500 mg/m2 (non-squamous) or paclitaxel 200 mg/m2 (squamous)) x 4 cycles followed by P 200 mg x 4 cycles, or the reverse sequence (arm B) of P x 4 cycles followed by C x 4 cycles. After 8 cycles, pts on both arms were eligible to receive maintenance P for up to 24 months. Primary endpoint was objective response rate (ORR) per RECIST 1.1 by independent review. Secondary endpoints included progression free survival (PFS) per RECIST 1.1 and overall survival (OS). Efficacy endpoints were also evaluated by PD-L1 expression. Results: 89 pts (47 arm B & 42 arm A) were enrolled and are included in the analysis (PD-L1 TPS 0/1-49%/≥50% = 24 pts (34%)/25 pts (36%)/21 pts (30%)). There was no significant difference in ORR (36% vs 38%, p = 0.829), median PFS (2.7 vs 5.5 months (mo), HR 1.25, 95% CI 0.77-2.02, p = 0.363) or OS (13.1 vs 19.8 mo, HR 1.25, 95% CI 0.69-2.25, p = 0.4573), arm B (Px4→C) vs arm A (Cx4→P). Multivariable Cox regression analysis demonstrated significant interaction between treatment and PD-L1 TPS ( < 50% vs ≥ 50%) for PFS (HR 6.76, 95% CI 2.14-21.35, p = 0.0011) and a trend for OS (HR 5.02, 95% CI 0.92-27.55, p = 0.0632), arm B vs arm A. Incidence of grade ≥3 adverse events was 71% for arm A and 65% for arm B. No new safety signals were observed. Conclusions: In pts with stage IV NSCLC and PD-L1 TPS ≥ 50% there was an observed improvement in PFS and OS in favor of C followed by P vs P x 4 followed by C. Given small # of pts and trial design, this observation should be considered hypothesis-generating, but supports further exploration of sequential C + P in this setting. Support:Merck Sharp & Dohme Corp.;