TY - JOUR
T1 - Blood tumor mutational burden and response to pembrolizumab plus chemotherapy in non–small cell lung cancer
T2 - KEYNOTE-782
AU - Bar, Jair
AU - Esteban, Emilio
AU - Rodríguez-Abreu, Delvys
AU - Aix, Santiago Ponce
AU - Szalai, Zsuzsanna
AU - Felip, Enriqueta
AU - Gottfried, Maya
AU - Provencio, Mariano
AU - Robinson, Andrew
AU - Fülöp, Andrea
AU - Rao, Suman Bannur
AU - Camidge, D. Ross
AU - Speranza, Giovanna
AU - Townson, Steven M.
AU - Kobie, Julie
AU - Ayers, Mark
AU - Dettman, E. J.
AU - Hunkapiller, Nathan
AU - McDaniel, Robert
AU - Jung, Byoungsok
AU - Burkhardt, David
AU - Mauntz, Ruth
AU - Csőszi, Tibor
N1 - Publisher Copyright:
© 2024 Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, The Author(s)
PY - 2024/4/1
Y1 - 2024/4/1
N2 - Background: First-line pembrolizumab plus chemotherapy has shown clinical benefit in patients with metastatic non–small cell lung cancer (NSCLC) regardless of tissue tumor mutational burden (tTMB) status. Blood tumor mutational burden (bTMB), assessed using plasma-derived circulating tumor DNA (ctDNA), may be a surrogate for tTMB. The KEYNOTE-782 study evaluated the correlation of bTMB with the efficacy of first-line pembrolizumab plus chemotherapy in NSCLC. Methods: Previously untreated patients with stage IV nonsquamous NSCLC received pembrolizumab 200 mg plus pemetrexed 500 mg/m2 and investigator's choice of carboplatin area under the curve 5 mg/mL/min or cisplatin 75 mg/m2 for 4 cycles, then pembrolizumab plus pemetrexed for ≤31 additional cycles every 3 weeks. Study objectives were to evaluate the association of baseline bTMB with objective response rate (ORR) (RECIST v1.1 by investigator assessment; primary), progression-free survival (PFS; RECIST v1.1 by investigator assessment), overall survival (OS), and adverse events (AEs; all secondary). A next-generation sequencing assay (GRAIL LLC) with a ctDNA panel that included lung cancer-associated and immune gene targets was used to measure bTMB. Results: 117 patients were enrolled; median time from first dose to data cutoff was 19.3 months (range, 1.0–35.5). ORR was 40.2 % (95 % CI 31.2–49.6 %), median PFS was 7.2 months (95 % CI 5.6–9.8) and median OS was 18.1 months (95 % CI 13.5–25.6). Treatment-related AEs occurred in 113 patients (96.6 %; grade 3–5, n = 56 [47.9 %]). Of patients with evaluable bTMB (n = 101), the area under the receiver operating characteristics curve for continuous bTMB to discriminate response was 0.47 (95 % CI 0.36–0.59). Baseline bTMB was not associated with PFS or OS (posterior probabilities of positive association: 16.8 % and 7.8 %, respectively). Conclusions: AEs were consistent with the established safety profile of first-line pembrolizumab plus chemotherapy in NSCLC. Baseline bTMB did not show evidence of an association with efficacy.
AB - Background: First-line pembrolizumab plus chemotherapy has shown clinical benefit in patients with metastatic non–small cell lung cancer (NSCLC) regardless of tissue tumor mutational burden (tTMB) status. Blood tumor mutational burden (bTMB), assessed using plasma-derived circulating tumor DNA (ctDNA), may be a surrogate for tTMB. The KEYNOTE-782 study evaluated the correlation of bTMB with the efficacy of first-line pembrolizumab plus chemotherapy in NSCLC. Methods: Previously untreated patients with stage IV nonsquamous NSCLC received pembrolizumab 200 mg plus pemetrexed 500 mg/m2 and investigator's choice of carboplatin area under the curve 5 mg/mL/min or cisplatin 75 mg/m2 for 4 cycles, then pembrolizumab plus pemetrexed for ≤31 additional cycles every 3 weeks. Study objectives were to evaluate the association of baseline bTMB with objective response rate (ORR) (RECIST v1.1 by investigator assessment; primary), progression-free survival (PFS; RECIST v1.1 by investigator assessment), overall survival (OS), and adverse events (AEs; all secondary). A next-generation sequencing assay (GRAIL LLC) with a ctDNA panel that included lung cancer-associated and immune gene targets was used to measure bTMB. Results: 117 patients were enrolled; median time from first dose to data cutoff was 19.3 months (range, 1.0–35.5). ORR was 40.2 % (95 % CI 31.2–49.6 %), median PFS was 7.2 months (95 % CI 5.6–9.8) and median OS was 18.1 months (95 % CI 13.5–25.6). Treatment-related AEs occurred in 113 patients (96.6 %; grade 3–5, n = 56 [47.9 %]). Of patients with evaluable bTMB (n = 101), the area under the receiver operating characteristics curve for continuous bTMB to discriminate response was 0.47 (95 % CI 0.36–0.59). Baseline bTMB was not associated with PFS or OS (posterior probabilities of positive association: 16.8 % and 7.8 %, respectively). Conclusions: AEs were consistent with the established safety profile of first-line pembrolizumab plus chemotherapy in NSCLC. Baseline bTMB did not show evidence of an association with efficacy.
KW - Blood tumor mutational burden
KW - Cell-free nucleic acids
KW - Circulating tumor DNA
KW - Non-small cell lung cancer
KW - Pembrolizumab
UR - http://www.scopus.com/inward/record.url?scp=85186406154&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2024.107506
DO - 10.1016/j.lungcan.2024.107506
M3 - Article
C2 - 38422883
AN - SCOPUS:85186406154
SN - 0169-5002
VL - 190
JO - Lung Cancer
JF - Lung Cancer
M1 - 107506
ER -