Lilly’s CYRAMZA Announces Positive Phase III Results


Eli Lilly and Company (NYSE: LLY) today announced detailed results from REVEL, a global Phase III study of CYRAMZA (ramucirumab) in combination with chemotherapy in patients with second-line non-small cell lung cancer (NSCLC). Data from the trial were published today in The Lancet and also presented at the American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #LBA8006). REVEL is the first positive Phase III study of a biologic in combination with chemotherapy to demonstrate improved overall survival compared to chemotherapy alone in second-line NSCLC.

Lung cancer is the leading cause of cancer death in the U.S. and most other countries, and non-small cell lung cancer accounts for 85 percent of all lung cancer cases. It is estimated that approximately half of NSCLC patients are receiving treatment in the second-line setting. Despite currently available therapies, there continues to be a need for new second-line treatment options for patients with NSCLC.

“While there have been other recent Phase III studies that have evaluated the addition of a cytotoxic or targeted agent in previously-treated NSCLC patient populations, none have demonstrated improved overall survival in the total patient population,” said Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology. “We are pleased that CYRAMZA demonstrated a significant survival improvement in a difficult-to-treat patient population where there continues to be a major unmet medical need in both nonsquamous and squamous NSCLC patients..”

The international study included a total of 1,253 nonsquamous and squamous NSCLC patients from 26 countries on six continents. Overall survival (OS) was the trial’s primary endpoint and secondary endpoints included progression-free survival (PFS) and objective response rate (ORR).

Patients treated on the CYRAMZA-plus-docetaxel arm (n=628) achieved a median OS of 10.5 months compared to 9.1 months for patients on the placebo-plus-docetaxel arm (n=625). The OS hazard ratio was 0.86 (95% CI, 0.751-0.979, p=0.023), which corresponds to a 14 percent reduction in risk of death.

Median PFS was 4.5 months on the CYRAMZA-plus-docetaxel arm compared to 3.0 months on the placebo-plus-docetaxel arm, with a PFS hazard ratio of 0.76 (p<0.001), which corresponds to a 24 percent reduction in risk of progression or death. ORR was 23 percent on the CYRAMZA-plus-docetaxel arm and 14 percent on the placebo-plus-docetaxel arm (p<0.0001).

“In the REVEL study, CYRAMZA demonstrated statistically significant improvement across multiple efficacy endpoints including overall survival, progression-free survival and overall response rate. The improvement of overall survival and progression-free survival on the CYRAMZA-plus-docetaxel arm was also consistent across the majority of subgroups including histology,” saidMaurice Perol, M.D., of the Leon-Berard Cancer Centre in France and co-lead investigator of the REVEL study. “Overall, these results are very encouraging for those of us who treat lung cancer patients.”

The most common (>5% incidence) Grade >/=3 adverse events occurring more frequently in patients on the CYRAMZA arm were neutropenia (48.8% vs. 39.8%), febrile neutropenia (15.9% vs. 10.0%), fatigue (14.0% vs 10.5%), leukopenia (13.7% vs. 12.5%), and hypertension (5.6% vs. 2.1%). Grade 5 adverse events were comparable between arms (5.4% vs. 5.8%). Patients on the CYRAMZA arm experienced more bleeding/hemorrhage events (all grade) (28.9 % vs 15.2%) but the rate of Grade >/=3 bleeding / hemorrhage events were similar between arms (2.4% vs 2.3%).

Dr. Perol presented the REVEL data at ASCO and Edward Garon, M.D., director of the Thoracic Oncology Program at the David Geffen School of Medicine at UCLA / Translational Oncology Research Laboratory and co-lead investigator of the REVEL study, is the lead author in The Lancet publication of the data.

Lilly intends to submit the first application of these data to regulatory authorities in the second half of 2014.