NCCN Recommends Biomarker Testing for All Patients with Newly Diagnosed Non–Small-Cell Lung Cancer

Wayne Kuznar

May 2017, Vol 7, No 5 - NCCN Conference Highlights


Orlando, FL—Molecular analysis and PD ligand 1 (PD-L1) testing for patients with non–small-cell lung cancer (NSCLC) are critically important. Optimally, multiple biomarker testing should be done at diagnosis, but it also has value before choosing therapy for second-line or later.

Even with upfront testing, “over the last year and a half, we’ve learned that you actually have to test biomarkers again during the course of disease, and the best example of that we have is with patients with EGFR-mutated lung cancer,” said Gregory J. Riely, MD, PhD, Vice Chair, Clinical Trials Office, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, at the 2017 National Comprehensive Cancer Network (NCCN) annual conference.

Molecular analysis and PD-L1 testing are central to guiding first-line treatment of NSCLC with targeted therapy, such as pembrolizu­mab (Keytruda) or with platinum-based chemotherapy, said Dr Riely. This strategy is in accordance with the most recent version (version 5.2017) of the NCCN guideline for the management of NSCLC, which recommends molecular testing of all histologic subtypes of lung cancer.

The NCCN guideline specifies testing for EGFR and ROS1 mutations, but “testing should be conducted as part of a broad molecular profiling program,” Dr Riely said.

Immunohistochemistry Is the PD-L1 Test

As a biomarker for drug efficacy, immunohistochemistry testing has not traditionally been used in lung cancer.

“Over the last year or so, we really discovered that we need to do an immunohistochemistry test, and that immunohistochemistry test is the PD-L1 test,” said Dr Riely. The PD-L1 test “decides whether a patient has enough of the marker to warrant initial immunotherapy,” he added.

The first-line use of pembrolizumab has broached the field of PD-L1 testing. Expression of PD-L1 ≥50% was shown to be a sensitive marker for the efficacy of pembrolizumab; the use of pembrolizumab in the subset of patients with ≥50% PD-L1 expression led to an improvement in overall survival compared with platinum-based chemotherapy; setting the bar at ≥5% PD-L1 expression did not improve outcomes with pembroliz­umab over conventional therapy.

PD-L1 testing “is all over the map,” with multiple antibodies for PD-L1 typically linked to a drug in development, said Dr Riely. Anti–PD-L1 testing stained with SP142 was recently shown to be discordant with the PD-L1 assays 22c3 and E1L3N.

The NCCN recommendation is to perform PD-L1 testing in patients with newly diagnosed NSCLC; because PD-L1 is probably “stable,” there is no clear benefit to repeat biopsy for assessment of PD-L1 unless the previous sample is exhausted, he said.

Testing to Guide Treatment

In 2017, routine, broad testing for driver oncogenes should be the standard of care for patients with NSCLC, according to the NCCN. Lung cancer associated with EGFR, ALK, or ROS1 mutations are examples of oncogene-addicted lung cancers. In numerous clinical trials, EGFR tyrosine kinase inhibitors (TKIs) were shown to be superior to platinum-based doublet chemotherapy in patients with EGFR mutation–positive NSCLC. If EGFR mutations are missed upfront, “it’s good to get these results even at a second line, so you can offer that patient the appropriate therapy,” said Dr Riely.

In addition to detecting PD-L1 and EGFR mutations, immunohistochemistry can be used to detect ALK and ROS1 mutations. FISH (fluorescence in situ hybridization) testing can be used to detect ALK, ROS1, and RET rearrangements, and DNA sequencing is useful for identifying any gene mutation. Biomarker testing needs to be customized to the institution, often with a combination of techniques, with the goal of providing results to the treating physician within 10 days.

Repeat Testing

All patients will have acquired resistance to EGFR TKIs, and need to repeat molecular profiling at the time of treatment resistance to first-line EGFR TKI. In more than 60% of patients with EGFR mutation–positive NSCLC, EGFR T790M is the second mutation that occurs. Patients’ plasma should be tested for the T790M mutation at clinical progression to determine which patients are candidates for second-line treatment with osimertinib (Tagrisso) or who should undergo biopsy with tumor EGFR testing.

Patients with the EGFR T790M mutation should receive osimertinib, whereas patients without this mutation should receive chemotherapy, advised Dr Riely. Osimertinib is now considered a standard of care (category 1 recommendation) in the NCCN guideline for patients with the EGFR T790M mutation who had previously received an EGFR inhibitor.