Small but Statistically Significant Improvement in Overall Survival With Second-Line Addition of Ramucirumab to Docetaxel in Stage IV NSCLC

Editor’s note: This article covers the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to test the effectiveness of adding a drug called ramucirumab (aka Cyramza) to treatment with the chemotherapy drug docetaxel. The patients who participated all had non-small cell lung cancer (NSCLC) that had worsened during platinum-based chemotherapy. The researchers found that ramucirumab provided patients with a small but significant improvement in survival time.

“In the phase III REVEL trial reported in The Lancet, Garon et al found that the addition of the  antiangiogenic VEGFR-2 inhibitor ramucirumab (Cyramza) to docetaxel produced a statistically significant improvement in overall survival as second-line treatment in patients with stage IV non–small cell lung cancer (NSCLC) after progression on platinum-based therapy…

“In this double-blind trial, 1,253 patients with squamous or nonsquamous stage IV NSCLC from academic medical centers and community clinics in 26 countries on six continents were randomly assigned between December 2010 and January 2013 to receive docetaxel at 75 mg/m² and either ramucirumab at 10 mg/kg (n = 628) or placebo (n = 625) on day 1 of 21-day cycles until disease progression, unacceptable toxicity, withdrawal, or death. Patients had to have progressed during or after a single platinum-based chemotherapy regimen, with or without bevacizumab (Avastin) or maintenance therapy.

“Randomization was stratified by sex, region, performance status, and previous maintenance therapy. The primary endpoint was overall survival in the intent-to-treat population.”


Adding Ziv-Aflibercept to Topotecan Improves Progression-Free Survival but Increases Toxicity in Platinum-Treated Small Cell Lung Cancer

Editor’s note: A recent clinical trial with volunteer patients tested whether a treatment that combines a drug called ziv-aflibercept (Zaltrap) with the drug topotecan would be better than toptecan alone for people with small cell lung cancer (SCLC). All participating patients had previously been treated with platinum-based chemotherapy and had been treated for brain metastases. Patients were randomly assigned to be treated with either topotecan alone, or the topotecan/ziv-aflibercept combination. The researchers found that the combination treatment significantly increased the number of patients who survived three months or more without their disease worsening. However, the combo treatment had worse side effects and did not improve overall survival.

“The phase II Southwest Oncology Group (SWOG) S0802 trial reported in the Journal of Clinical Oncology by Allen et al showed that adding ziv-aflibercept (Zaltrap) to topotecan improved 3-month progression-free survival, but increased toxicity and had no effect on overall survival, in patients with platinum-treated small cell lung cancer (SCLC)…

“In the trial, 189 patients who had experienced disease progression after one line of platinum-based chemotherapy and had treated brain metastases, Eastern Cooperative Oncology Group performance status of 0 or 1, and no recent vascular events or bleeding diatheses were randomly assigned to receive weekly topotecan at 4 mg/m2 with (n = 97) or without (n = 92) ziv-aflibercept at 6 mg/kg every 21 days. Patients were stratified as platinum-refractory (n = 55 vs 51) or platinum-sensitive (n = 42 vs 41). Progression-free survival at 3 months was the primary endpoint.”


Cyramza Yields a Modest Survival Benefit in Second-line NSCLC

“Cyramza™ (ramucirumab, IMC-1121B; Eli Lilly) is a human IgG1 monoclonal antibody directed against the extracellular domain of VEGFR-2. It was recently approved by the Food and Drug Administration (FDA) for advanced gastric cancer or gastroesophageal junction adenocarcinoma. On February 19, 2014, Lilly announced via press release that the REVEL trial was positive for both overall survival (OS) and progression-free survival (PFS) benefit. Results from the randomized, double-blind, placebo-controlled Phase III REVEL trial (NCT01168973) were reported at the 2014 annual meeting of the American Society of Clinical Oncology (ASCO). The trial evaluated docetaxel with or without Cyramza in squamous or non-squamous Stage IV non-small cell lung cancer (NSCLC) patients following disease progression after one prior platinum-based therapy.”

Editor’s note: A new targeted drug called Cyramza (aka ramucirumab) shows promise as a potential treatment for people with advanced non-small cell lung cancer (NSCLC). In a clinical trial, scientists tested the drug on volunteer patients with stage IV NSCLC. Compared to standard chemotherapy alone, patients who were treated with chemo plus Cyramza lived longer and had more time pass before their cancer worsened.

Update 6/9/14: According to Dr. Jack West of GRACE, the benefit of Cyramza is very minimal in the above-mentioned clinical trial, and is therefore not so promising.


ELCC 2014 News: Cabazitaxel Fails to Meet the Primary Endpoint in a Randomised Phase II Study in SCLC Patients

“Cabazitaxel failed to meet a primary endpoint of showing superior progression-free survival (PFS) and additionally showed less favourable median overall survival (OS) compared to topotecan in an international, randomised open-label phase II trial performed in patients with small-cell lung cancer (SCLC), who had progressed during or after first-line platinum-based chemotherapy. The results were presented by Dr Tracey Evans of the Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, USA in a proffered papers session at the 4th European Lung Cancer Conference (26-29 March 2014, Geneva, Switzerland).”

Editor’s note: This trial found disappointing results for the drug cabazitaxel in treating small cell lung cancer (SCLC). To read about promising SCLC treatments, see this blog feature.


Cetuximab Plus Chemotherapy Effective in NSCLC

“The addition of cetuximab to platinum-based first-line chemotherapy significantly improved outcomes in patients with advanced non–small cell lung cancer, according to results of a meta-analysis.

“The regimen also appeared well tolerated.”