Kate Johnson

May 31, 2014

CHICAGO — The antiangiogenic drug ramucirumab (Cyramza, Eli Lilly) marginally improved survival in the second-line treatment of non-small cell lung cancer (NSCLC), according to a company-sponsored REVEL study.

The clinical meaningfulness of this was the subject of discussion during a press conference here at the 2014 Annual Meeting of the American Society of Clinical Oncology® (ASCO).

Dr. Maurice Pérol

"This represents a new therapeutic option for patients with advanced non-small cell lung cancer," reported lead author Maurice Pérol, MD, head of thoracic oncology at the Cancer Research Center of Lyon in France. "This is the first treatment in approximately a decade to improve the outcome of patients in the second-line setting. There is a large unmet medical need in this setting."

"It's exciting to see progress in this disease, where the steps are small but cumulative," said session moderator Gregory Masters, MD, from the Helen F. Graham Cancer Center in Newark, Delaware, and an ASCO expert in lung and head and neck cancers. "We're excited to have another agent that shows activity, especially in this very difficult-to-treat population."

However, in a subsequent interview with Medscape Medical News, Dr. Masters acknowledged that the drug's overall survival benefit of 1.4 months and progression-free survival benefit of 1.5 months is "very small."

"Sometimes we have to make a little progress and try to build on that," he said.

The 1253 patients enrolled in REVEL had stage IV NSCLC that had recurred despite standard chemotherapy; all received docetaxel 75 mg/m².

The patients were randomized to receive ramucirumab 10 mg/kg on day 1 of a 21-day cycle or placebo until disease progression, unacceptable toxicity, or death.

Overall survival, the primary end point, was better in the ramucirumab group than in the placebo group (10.5 vs 9.1 months; hazard ratio [HR], 0.857). This translated to a mortality risk reduction of 14% (P = .0235).

Median progression-free survival was also better in the ramucirumab group (4.5 vs 3.0; HR, 0.762), with a 24% reduction in the risk for progression (P < .0001).

Survival benefits were consistent across the major subgroups of patients, including those with squamous and nonsquamous disease.

"You have to remember that this is in the context of second-line treatment," Dr. Pérol told Medscape Medical News after the presentation. "That means patients with response rates consistently less than 10% and median progression-free survival consistently less than 3%. It is a small difference, but for a very large number of patients."

"It is both exciting and encouraging to see positive results in the setting of advanced lung cancer," said Natasha Leighl, MD, medical oncologist at the Princess Margaret Hospital/University Health Network and assistant professor in the Department of Medicine at the University of Toronto.

"This study is unique, in that this is the first time a VEGF or VEGFR inhibitor has improved outcome in advanced squamous lung carcinoma patients," she told Medscape Medical News. "The key issue in moving forward with these study results will be whether clinicians, patients, and payors believe that the magnitude of improvement is sufficient to make this combination a new standard of care."

The increase in overall survival of 1.5 months with ramucirumab "is clinically relevant," said Giuseppe Giaccone, MD, PhD, associate director of clinical research at the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC.

However, there was some discussion about this in light of the recent ASCO statement about defining clinically meaningful outcomes (J Clin Oncol. 2014;32:1277-1280).

According to the statement, the survival benefit for lung cancer should be 2.5 to 4.0 months to be considered clinically meaningful. The REVEL results do not meet that standard.

But that standard was for first-line, not second-line, treatment. "It's wrong to extrapolate," said ASCO expert Don Dizon, MD, from Massachusetts General Hospital in Boston.

"In the first-line setting, clinically meaningful outcomes are defined as 3 to 4 months for lung cancer, but would you expect that in the second-line setting? Probably not. The thresholds of importance are different," Dr. Dizon told Medscape Medical News.

Ramucirumab was recently approved by the US Food and Drug Administration for the treatment of gastric cancer.

The study was supported by ImClone, a wholly owned subsidiary of Eli Lilly. Dr. Pérol reports financial relationships with Boehringer Ingelheim, Genentech, Lilly, Pfizer, and Roche. Dr. Masters, Dr. Giaccone, and Dr. Dizon have disclosed no relevant financial relationships.

2014 Annual Meeting of the American Society of Clinical Oncology (ASCO): Abstract LBA8006. Presented June 1, 2014.

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