Ramucirumab plus chemotherapy improved outcomes in advanced NSCLC

CHICAGO — Second-line ramucirumab added to standard docetaxel chemotherapy significantly improved response rate, PFS and OS in patients with advanced non–small cell lung cancer, according to results of the phase 3 REVEL trial presented at the ASCO Annual Meeting.

Perspective from Gregory A. Masters, MD, FACP

“Despite the advances in the field of personalized medicine, oncogenesis arising from a single genetic targetable abnormality still affects the minority of patients with lung cancer,” study researcher Maurice Pérol, MD, head of thoracic oncology at Cancer Research Center of Lyon in France, said during a press conference. “The majority of these patients have not benefited from targeted therapy, and for these patients the treatment of choice is chemotherapy. No other trials evaluating the addition of a new agent to standard second-line chemotherapy have demonstrated an improvement of OS outside of subgroup analyses; therefore, there is a large unmet medical need in this setting.”

The analysis included 1,253 patients with stage IV squamous (26.2%) or non-squamous (78.3%) NSCLC who progressed after platinum-based therapy.

Pérol and colleagues randomly assigned 628 patients 75 mg/m² docetaxel plus 10 mg/kg ramucirumab (Cyramza, Eli Lilly) — a monoclonal antibody that targets the VEGF receptor 2 — on day 1 of 21-day cycles until disease progression, unacceptable toxicity or death. The other 625 patients received docetaxel plus placebo.

Overall, researchers reported a significantly higher objective response rate in the ramucirumab arm (22.9% vs. 13.6%; P˂.001).

Patients assigned ramucirumab demonstrated significantly longer median PFS (4.5 months vs. 3 months; HR=0.762; P<.0001) and OS (10.5 months vs. 9.1 months; HR=0.857; 95% CI, 0.751-0.98) compared with those assigned placebo.

The survival benefit associated with ramucirumab was observed among patients with squamous and non-squamous histology, Pérol said.

More patients in the ramucirumab arm experienced grade ≥3 neutropenia (34.9% vs. 28%), febrile neutropenia (15.9% vs. 10%), fatigue (11.3% vs. 8.1%), leukopenia (8.5% vs. 7.6%) and hypertension (5.4% vs. 1.9%). Pneumonia occurred in 5.1% of patients assigned ramucirumab and 5.8% of patients assigned placebo.

Researchers observed similar rates of grade 5 adverse events (5.4% for ramucirumab vs. 5.8% for placebo). Rates of pulmonary hemorrhage of any grade were similar among the entire patient population (2.1% for ramucirumab vs. 1.6% for placebo) and among those with squamous histology (3.8% for ramucirumab vs. 2.4% for placebo).

“The addition of ramucirumab to docetaxel represents the first combination since a decade that demonstrated a significant OS benefit over chemotherapy alone in second-line setting,” Pérol told HemOnc Today. “This is an important new therapeutic option in a setting with very limited options.” - by Sasha Todak

For more information:

Pérol M. Abstract #LBA8006. Presented at: ASCO Annual Meeting; May 30-June 3, 2014; Chicago.

Disclosure: The study was funded by ImClone, a wholly owned subsidiary of Eli Lilly. The researchers report consultant/advisory roles and employment/leadership positions with; honoraria, research funding or other remuneration from; and stock ownership in Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Clovis, Genentech, ImClone Systems, Lilly, Pfizer and Roche.

Perspective

Gregory A. Masters, MD, FACP

This study expands the treatment options for patients with recurrent or refractory NSCLC. Ramucirumab is an effective targeted agent when added to chemotherapy, with low toxicity. This will be a significant benefit to those patients whose cancer progresses following initial chemotherapy.

What we try to focus on in designing clinical trials is to come up with more effective therapies, and to make progress in the diseases as we understand the disease better, and try to target therapies at our understanding of the ways tumors can grow and progress. The progress that’s being made in lung cancers and in many cancers is slow, and is a step-wise progress. We try to build on those steps one bit at a time, and I think it’s the cumulative understanding of the diseases, and the cumulative progress, that we find most encouraging. Each individual trial is only one small step; it doesn’t necessarily mean that an individual study with a small improvement in survival will automatically change the entire way that we treat patients, but it can influence clinical trials and it can influence our understanding of how drugs work and which drugs are most worthy of further study.

Our understanding of using targeted drugs will build on our ability to make more progress and to help patients better. We do have to balance the small benefits and the costs. We need to continue to make progress to figure out how this drug works in, but it’s not necessarily going to change the way patients are treated tomorrow.

Gregory A. Masters, MD, FACP

Medical oncologist, Helen F. Graham Cancer Center

Newark, Del.

Member, ASCO Cancer Communications Committee

Disclosures: Masters reports no relevant financial disclosures.