Blood tumor mutational burden and response to pembrolizumab plus chemotherapy in non–small cell lung cancer: KEYNOTE-782

Jair Bar*, Emilio Esteban, Delvys Rodríguez-Abreu, Santiago Ponce Aix, Zsuzsanna Szalai, Enriqueta Felip, Maya Gottfried, Mariano Provencio, Andrew Robinson, Andrea Fülöp, Suman Bannur Rao, D. Ross Camidge, Giovanna Speranza, Steven M. Townson, Julie Kobie, Mark Ayers, E. J. Dettman, Nathan Hunkapiller, Robert McDaniel, Byoungsok JungDavid Burkhardt, Ruth Mauntz, Tibor Csőszi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number107506
JournalLung Cancer
StatePublished - Apr 2024


FundersFunder number
Kristina Maiuri
Merck Sharp & Dohme LLC


    • Blood tumor mutational burden
    • Cell-free nucleic acids
    • Circulating tumor DNA
    • Non-small cell lung cancer
    • Pembrolizumab


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