October 2016 Edition Vol.11, Issue 10

At ESMO: One Anti-PD1 Agent Moves to the Head of the Line in Advanced NSCLC

At ESMO: In Advanced NSCLC, One Anti-PD1 Agent Moves to the Front of the Line (cont.)

Nivolumab Studies

The first-line study of nivolumab, however, failed to live up to expectations set by its earlier trials, when CheckMate 026 failed to show an improvement in PFS for single-agent nivolumab versus a platinum-based doublet.

The trial randomized 541 PD-L1-positive patients (≥1% PD-L1) to nivolumab (3 mg/kg) or chemotherapy by physician’s choice.

“Nivolumab did not meet the primary endpoint of superior PFS compared with chemotherapy in patients with PD-L1 expression ≥5%,” reported Mark Socinski, MD, Executive Medical Director of Florida Hospital Cancer Institute.

Median PFS was 4.2 months with nivolumab and 5.9 months with chemotherapy (HR=1.15; P=.2511). Median overall survival was also similar: 14.4 months versus 13.2 months (HR=1.02; 95% CI, 0.80, 1.30; no P value was shown).

Crossover was allowed, and 57% of the chemotherapy arm ultimately received nivolumab on study. Responses were observed in 26.1% and 33.5%, respectively, with median duration of response being 12.1 months and 5.7 months. Treatment-related events, however, were much less with nivolumab.

Atezolizumab Trials

Also reported at ESMO were first results from the phase 3 OAK study of atezolizumab versus docetaxel as second- and third-line treatment in 1,225 patients.

Atezolizumab received Breakthrough Therapy designation earlier this year and is currently under priority review with the FDA for late-line treatment of PD-L1-positive patients.

Median OS was superior with atezolizumab: 13.8 months versus 9.6 months with docetaxel (HR=0.73; P=0.0003); in patients with PD-L1 expression ≥1%, OS was 15.7 months versus 10.3 months, respectively (HR=0.74; P=0.0102, and was improved regardless of PD-L1 expression levels. Even PD-L1-negative patients derived benefit (HR=0.75; P=0.0215).

Implications of Phase 3 Trials

Until now, nivolumab has often been the favored anti-PD1 agent in the second-line setting, since testing for PD-L1 expression is not required for its use. “Now, we will test all patients, and the results will determine what we do next,” said David Spigel, MD, Director of the Lung Cancer Research Program at Sarah Cannon Research Institute, Nashville.

“I will ask for the Merck PD-L1 assay in essentially 100% of my patients and they will get pembrolizumab if they are eligible…Pembrolizumab will become a new standard of care in the first-line setting for about one third of our patients—those with at least 50% expression of PD-L1.”

Roy Herbst, MD, PhD, Ensign Professor of Medicine (Medical Oncology), Professor of Pharmacology and Chief of Medical Oncology at Yale Cancer Center, agreed.

“Patients with targetable mutations should still get targeted treatment, but those who do not—whether squamous or non-squamous histology—should get pembrolizumab,” he said. “We predicted the biomarker would be important in the front-line setting, and we are seeing that today.”

This means that for all newly diagnosed advanced NSCLC patients, testing for PD-L1 expression will be required.

“Once pembrolizumab is approved,” Dr. Langer added, “PD-L1 assessment must be part of our diagnostic work-up, on a reflex and not reactive basis. Patients cannot wait for these results.”

The experts agreed, however, that pembrolizumab’s run as the preferred first-line treatment for non-mutated patients could be short-lived.

“I think that pembrolizumab will be the [favored] first-line drug for a while,” Dr. Spigel said, “but I think there will be better strategies than single-agent checkpoint inhibitors. I think ipilimumab plus nivolumab will yield higher response rates than either single agent alone…I think a year from now, when the combination data read out, there could be a new first-line treatment overtaking pembrolizumab and PD-L1 expression may not matter anymore. Combinations may show us we don’t need it.”

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For related lung cancer videos, please check out our coverage of the ASCO 2016 annual meeting:

     

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