September 2014, Vol 3, No 6
Ramucirumab Conveys Survival Benefit in NSCLCUncategorized
The investigational monoclonal antibody ramucirumab improved overall survival (OS) when added to docetaxel, versus chemotherapy alone, in patients with stage IV non-small cell lung cancer (NSCLC), according to a phase III trial highlighted in a press briefing at ASCO.
“This is the first treatment to have shown a significant survival advantage over chemotherapy alone in second-line therapy of NSCLC, and the first treatment in approximately a decade to improve outcomes in the second-line setting,” said Maurice Pérol, MD, head of thoracic oncology at Cancer Research Center of Lyon, France.
“This study met the primary endpoint of OS, reducing the risk of death by 14% and prolonging median survival by 1.4 months,” Pérol reported. The combination reduced the risk of progression by 24%.
“Ramucirumab represents a potential new option for treatment in the second-line setting,” Pérol suggested.
Ramucirumab, which recently became FDA-approved for advanced gastric cancer, targets VEGFR-2 and thus blocks the formation of new blood vessels to feed the tumor. If further studies validate these findings and the drug is approved by the FDA, it would be the first antiangiogenic drug approved for second-line NSCLC treatment.
The improvement in survival was demonstrated in patients with both squamous and nonsquamous histology – but the median OS benefit, though statistically significant, was quite modest. Nevertheless, he said the drug could be useful in patients lacking a specific mutation (EGFR, ALK) that would make them candidates for targeted therapy.
In EGFR-mutated patients, the approved second-line chemotherapy includes docetaxel, pemetrexed, and erlotinib and median OS with these agents is 7 to 9 months.
The double-blind, placebo-controlled, phase 3 REVEL trial enrolled 1253 patients with stage IV NSCLC (26% with squamous histology) that progressed on standard platinum-based therapy. Patients were randomized to treatment with ramucirumab plus docetaxel or docetaxel plus placebo.
The combination significantly improved response rate (RR), progression-free survival (PFS), and OS compared with docetaxel alone. The median PFS was 4.5 months with the novel agent versus 3 months without (P< 0.0001), and median OS was 10.5 months versus 9.1 months (P=0.0235), respectively.
The safety profile was in line with other angiogenesis inhibitors. No increase in pulmonary hemorrhage was observed with the combination.
Is 1.4 Months Additional Survival Meaningful?
“This combination shows good activity in the difficult-to-treat second-line setting of NSCLC,” said Gregory Masters, MD, of the Helen F. Graham Cancer Center, Newark, DE, who moderated a press conference where these data were presented.
Masters fielded questions regarding the drug’s true value, specifically, whether 1.4 months’ additional survival represented “value,” and especially in light of ASCO’s recent recommendation that new NSCLC treatments (in the first-line setting) extend survival by at least 3 months.
He responded that the drug may be a small step along the pathway that ultimately constitutes improvement. “Progress is slow and step-wise, and we build one step at a time. The cumulative progress is what we find encouraging…A study like REVEL may not change the way we treat NSCLC, but it can influence our design of further studies,” he said, adding that there is a mandate to “balance benefit with cost, and figure out how best to treat patients.”
Don Dizon, MD, of Massachusetts General Hospital, Boston, who represented ASCO at the press briefing, commented that the 3-month OS threshold is “guidance” but is not the “be-all and end-all” for investigational studies. “When we decide that a treatment has value, we consider three key things: efficacy, toxicity, and cost,” he said.
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