Abstract
Pembrolizumab vs placebo for early-stage non‒small-cell lung cancer after resection and adjuvant therapy: Subgroup analysis of patients who received adjuvant chemotherapy in the phase 3 PEARLS/KEYNOTE-091 study.
Author
person
Kersti Oselin
North Estonia Medical Centre, Tallinn, Estonia
info_outline
Kersti Oselin, Byoung Yong Shim, Morihito Okada, Maciej Bryl, Laura Bonanno, Guzin Demirag, Ida Colantonio, Martin Kimmich, Urska Janzic, Johan F. Vansteenkiste, Reyes Bernabe Caro, Amina Scherz, Alessandra Curioni-Fontecedro, Martin Früh, Mira Wollner, Jing Yang, Nazly Shariati, Sandrine Marreaud, Solange Peters, Mary ER O'Brien
Full text
Authors
person
Kersti Oselin
North Estonia Medical Centre, Tallinn, Estonia
info_outline
Kersti Oselin, Byoung Yong Shim, Morihito Okada, Maciej Bryl, Laura Bonanno, Guzin Demirag, Ida Colantonio, Martin Kimmich, Urska Janzic, Johan F. Vansteenkiste, Reyes Bernabe Caro, Amina Scherz, Alessandra Curioni-Fontecedro, Martin Früh, Mira Wollner, Jing Yang, Nazly Shariati, Sandrine Marreaud, Solange Peters, Mary ER O'Brien
Organizations
North Estonia Medical Centre, Tallinn, Estonia, The Catholic University of Korea, St. Vincent's Hospital, Suwon, Korea, Republic of (South), Hiroshima University Hospital, Hiroshima, Japan, Wielkopolskie Centrum Pulmonologii i Torakochirurgii im. Eugenii i Janusza Zeylandów, Poznań, Poland, Medical Oncology 2, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy, Ondokuz Mayıs Üniversitesi Tıp Fakültesi, Samsun, Turkey, Azienda Ospedaliera S. Croce e Carle Cuneo, Cuneo, Italy, Robert-Bosch-Krankenhaus - Klinik Schillerhöhe, Stuttgart, Germany, Klinika Golnik, Golnik, Slovenia, University Hospital KU Leuven Leuven, Leuven, Belgium, Hospital Universitario Virgen del Rocío, Sevilla, Spain, Inselspital, Universitätsspital Bern, Bern, Switzerland, Cantonal Hospital and University of Fribourg, Fribourg, Switzerland, Kantonsspital St. Gallen, St. Gallen, Switzerland, Rambam Medical Center, Haifa, Israel, Merck & Co., Inc., Rahway, NJ, European Organisation for Research and Treatment of Cancer, Brussels, Belgium, CHUV University Hospital of Lausanne, Lausanne, Switzerland, Lung Unit, Royal Marsden Hospital, London, United Kingdom
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA
Background:
In the randomized, triple-blind, phase 3 PEARLS/KEYNOTE-091 study (NCT02504372), at the second interim analysis, pembrolizumab (pembro) significantly prolonged DFS vs placebo (pbo) in the overall population of patients (pts) with completely resected stage IB–IIIA NSCLC per AJCC v7 who may or may not have received adjuvant chemotherapy (chemo; up to 4 cycles) as recommended per local guidelines (n = 1177; HR, 0.76 [95% CI, 0.63–0.91];
P
= 0.0014). Here we present outcomes for those pts who received 1–4 cycles of prior adjuvant chemo, per protocol.
Methods:
Eligible adults had pathologically confirmed, completely resected stage IB (T ≥4 cm), II, or IIIA NSCLC (AJCC v7) of any PD-L1 expression, ECOG performance status of 0 or 1, and had not received neoadjuvant radiotherapy or chemo. Pts were randomized 1:1 to pembro 200 mg or pbo Q3W for 18 doses (~1 year); receipt of adjuvant chemo (yes vs no) was one of the stratification factors. Dual primary endpoints were DFS in the ITT and PD-L1 TPS ≥50% populations. No alpha was assigned to this subgroup analysis of pts who received adjuvant chemo for 1–4 cycles per local guidelines.
Results:
Of 1177 pts in the ITT population, 1010 (85.8%) received adjuvant chemo and were included in this analysis (pembro, n = 506; pbo, n = 504). Pts received a median of 17 and 18 study doses, respectively. As of data cutoff (Sep 20, 2021), 52.6% in the pembro arm vs 64.9% in the pbo arm had completed treatment. Median time from randomization to data cutoff was 37.4 mo. Median (95% CI) DFS was 58.7 mo (39.2 mo–not reached [NR]) in the pembro arm vs 34.9 mo (28.6 mo–NR) in the pbo arm (HR, 0.73 [95% CI, 0.60–0.89]). Estimated 18-mo DFS rates were 73.8% and 63.1%, respectively. In pts with PD-L1 TPS ≥50% (pembro, n = 143; pbo, n = 141), median DFS was NR in both treatment arms (HR, 0.80 [95% CI, 0.54–1.20]). Grade 3–5 adverse events (AEs) occurred in 170 pts (34.3%) in the pembro arm and 128 (25.7%) in the pbo arm (grade 5, 2.2% vs 1.0%). Immune-mediated AEs and infusion reactions occurred in 195 pts (39.3%) in the pembro arm and 69 (13.8%) in the pbo arm.
Conclusions:
Consistent with the ITT population, pembro substantially improved DFS vs pbo in the subgroup of pts with stage IB (T2a ≥4 cm), II, or IIIA NSCLC who received adjuvant platinum-based chemo following complete resection. Based on these results, pembro was approved for adjuvant treatment in this pt population by the US FDA. Clinical trial information: NCT02504372.
Clinical status
Clinical
1 clinical trial
12 organizations
4 drugs
3 targets
Clinical trial
A Randomized, Phase 3 Trial With Anti-PD-1 Monoclonal Antibody Pembrolizumab (MK-3475) Versus Placebo for Patients With Early Stage NSCLC After Resection and Completion of Standard Adjuvant Therapy (PEARLS)Status: Active (not recruiting), Estimated PCD: 2023-01-24
Organization
North Estonia Medical Centre FoundationOrganization
The Catholic University of KoreaOrganization
Hiroshima University HospitalOrganization
Ondokuz Mayıs Üniversitesi Tıp FakültesiOrganization
Azienda Ospedaliera S. Croce e Carle CuneoOrganization
Robert-Bosch-Krankenhaus - Klinik SchillerhöheOrganization
Klinika GolnikOrganization
Merck & Co., Inc.Organization
Lung Unit, Royal Marsden HospitalDrug
pembrolizumabDrug
placeboDrug
CisplatinTarget
PD-1Target
PembrolizumabTarget
Placebo