LUNG CANCER

PD-L1 positivity predicts response

Immune-checkpoint inhibitors have substantially improved the outcomes of a subset of patients with non-small-cell lung cancer (NSCLC). However, the lack of a response in many patients, added to the high costs and risks of adverse events, indicates a need for better biomarkers to guide patient selection. Now, the outcomes of an open-label phase II trial, in which patients were stratified by programmed cell death 1 ligand 1 (PD-L1) expression, demonstrate the validity of this biomarker.

A total of 288 patients with recurrent stage IIIB or stage IV NSCLC without detectable EGFR or ALK alterations received 2-weekly nivolumab (3 mg/kg) plus 6-weekly ipilimumab (1 mg/kg) for ≥2 years or until disease progression or unacceptable toxicities. The overall response rate (ORR) was 30% among all patients including complete responses in 2.4% of patients, with a median progression-free survival (PFS) of 4.2 months. The ORR among patients with PD-L1 expression on ≥1% of tumour cells was 41% versus 15% in those with tumour PD-L1 <1%. Similarly, among the 98 patients with sufficient tumour material available to evaluate tumour mutational burden (TMB), those with a TMB ≥10 mutations per megabase (mut/Mb) had an ORR of 44% versus 12% in those with a TMB <10 mut/Mb. PD-L1 expression did not affect the response rate of patients with a TMB ≥10 mut/Mb (ORR 48% in patients with PD-L1 ≥1% versus 47% in those with PD-L1 <1%). Grade ≥3 treatment-related adverse effects (TRAEs) were observed in 29% of patients; 15.6% of patients discontinued both agents owing to such events.

These findings demonstrate the efficacy of combining immune-checkpoint inhibition in the first-line setting for patients with metastatic NSCLC. The substantially improved response rates of patients with ≥1% PD-L1 expression provide a potential biomarker to guide the selection of patients who are most likely to benefit from this combination.

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  1. Ready, N. et al. First-line nivolumab plus ipilimumab in advanced non-small-cell lung cancer (CheckMate 568): outcomes by programmed death ligand 1 and tumor mutational burden as biomarkers. J. Clin. Oncol. https://doi.org/10.1200/JCO.18.01042 (2019)

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Correspondence to Peter Sidaway.

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Sidaway, P. PD-L1 positivity predicts response. Nat Rev Clin Oncol 16, 337 (2019). https://doi.org/10.1038/s41571-019-0199-z

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