Expert Point of View: Solange Peters, MD, PhD

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Solange Peters, MD, PhD

Solange Peters, MD, PhD, of the Lausanne University Hospital, Switzerland, put these updates in context of what is known about programmed cell death protein 1 (PD-1) antibodies in non–small cell lung cancer (NSCLC), concluding that nivolumab (Opdivo) is “one of the best options” for advanced/metastatic disease. The CheckMate 017 and CheckMate 063 “tails of the curve” are consistent and suggest that long-term survival may be achievable in at least one-quarter of patients, she noted.

“In the past 15 years, there have been a number of randomized phase III trials challenging docetaxel as the standard of care.… Some have been positive,” added Dr. Peters.

These trials showed, in unselected squamous cell populations, median overall survival of 7.9 months with afatinib (Gilotrif), 6.8 months with erlotinib, 6.3 months with docetaxel alone, and 9.5 months with docetaxel plus ramucirumab (Cyramza). Nivolumab as a single agent yielded a median survival of 9.2 months in unselected patients, with much better tolerability than docetaxel, she pointed out.

“I can conclude two things,” stated Dr. Peters. “One is that nivolumab represents one of the best options you have for second-line treatment. Second is that unselected squamous cell cancer of the lung remains a disease characterized by a high unmet medical need.”

The community-based study also showed that “the elderly, PS2 [performance status of 2], pretreated patients, regardless of histology, can benefit from nivolumab, and with a similar safety profile,” she said, adding that it will be important to see patient-related outcome data.

Search for the Right Biomarker

The pressing question, Dr. Peters continued, is whether PD-L1 (ligand of PD-1) expression is the right biomarker for nivolumab. Other options to be considered include tumor mutational load, presence of tumor-infiltrating lymphocytes, and tumor molecular characteristics.

Moreover, she emphasized that PD-L1 positivity is “a flexible concept” that depends on sampling, assays, interpretation, and more. The survival benefit with nivolumab has been independent of its expression in squamous cell cancers, she said.

Dr. Peters suggested that immunotherapy must induce a T-cell response, and this may be more likely when PD-1 antibodies are combined with other immunotherapy strategies. Even then, patient selection may be a pipe dream.

“Are we ready to select patients for these treatments?” she asked. “The complexity of immune surveillance and escape might prevent us from identifying a simple and unique predictive biomarker.” ■

Disclosure: Dr. Peters reported relationships with Bristol-Myers Squibb, F. Hoffmann-La Roche, Eli Lilly, AstraZeneca, Pfizer, Boehringer-Ingelheim, Daiichi-Sankyo, Morphotek, Merrimack, Merck Sharp and Dohme, and Merck Serono.


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Nivolumab in Lung Cancer Supported by Updated Trial Data

For the treatment of advanced squamous non–small cell lung cancer (NSCLC), the programmed cell death protein 1 (PD-1) antibody nivolumab (Opdivo) continues to show results in key trials that now report 18-month data. The updates were reported at the 16th World Conference on Lung Cancer in Denver,...