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Updated NSCLC Guidelines Incorporate PD-L1 Testing and Molecular Assays

Wayne Kuznar
Published: Tuesday, May 30, 2017
Gregory J. Riely, MD, PhD

Gregory J. Riely, MD, PhD

Updates to the National Comprehensive Cancer Network (NCCN) guidelines for the management of advanced non–small cell lung cancer (NSCLC) call for routine molecular analysis and testing for PD-L1 expression, preferably at diagnosis. According to version 5.2017 of the NCCN guidelines,1 multiplexed biomarker testing is critically important to the selection of appropriate firstline and subsequent lines of therapy.

-mutant advanced NSCLC develop acquired resistance to an EGFR tyrosine kinase inhibitor (TKI), another molecular analysis is recommended at the time of resistance.

Initial Evaluation: PD-L1 Testing and Molecular Analysis

The latest version of the guidelines recommends that PD-L1, in addition to molecular analysis, be employed as a biomarker to direct initial therapy, with ≥50% expression established as the threshold for a positive result. The PD-L1 test “decides whether a patient has enough of the marker to warrant initial immunotherapy,” Riely said.

In addition, PD-L1 expression is likely stable, he said, so there is no clear benefit to a repeat biopsy for assessment of PD-L1 unless the prior sample has been exhausted. In the case of molecular analysis, Riely suggested that institutions should customize their approach. Many use a combination of immunohistochemistry, fluorescence in situ hybridization, and DNA sequencing to detect abnormalities in key genes.

Treatment Algorithm

Based on the results of PD-L1 testing and molecular analysis, the NCCN developed an algorithm for initial therapy for patients with stage IV NSCLC. Patients with EGFR, ALK, or ROS1 mutations or rearrangements at diagnosis, which collectively constitute about 25% of NSCLC, should receive targeted therapy as first-line treatment (Table 1).


Table 1. Biomarker-Driven Frontline Therapy for Metastatic NSCLC

 Biomarker-Driven Frontline Therapy for Metastatic NSCLC
Pembrolizumab (Keytruda) is recommended as a first-line choice for patients with NSCLC whose tumors are positive for PD-L1 while being negative or unknown for mutations or rearrangements in EGFR, ALK, and ROS1 (category 1 recommendation). This recommendation is based on the results of the KEYNOTE-024 trial, which proved pembrolizumab superior to a platinum doublet combination on the endpoint of median progression-free survival (PFS; 10.3 vs 6.0 months; P <.001) as first-line therapy in patients with NSCLC with PD-L1 expression ≥50%. (At press time, the guidelines had not been updated to reflect the May 10 approval of pembrolizumab in combination with pemetrexed and carboplatin for previously untreated patients, regardless of PD-L1 expression).
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