Eli Lilly today detailed the extent to which its marketed oncology drug Cyramza® (ramucirumab), assessed as second-line treatment following Nexavar® (sorafenib), failed a Phase III trial—yet generated positive results within a patient subgroup.

Cyramza missed its primary endpoint of a statistically significant improvement in overall survival (OS) in patients with liver cancer. The REACH trial's primary endpoint of overall survival favored the Cyramza arm, but the improvement was not statistically significant, Lilly said. Median OS was 9.2 months on the trial’s ramucirumab arm compared to 7.6 months on the placebo arm.

Lilly disclosed topline results last year of Cyramza’s disappointing outcome in hepatocellular carcinoma (HCC). Yesterday, detailed results from the Phase III trial were published in The Lancet Oncology.

Those results also showed encouraging single-agent Cyramza activity, with meaningful improvements in key secondary endpoints as well as within certain patient subgroups. The REACH trial defined key secondary endpoints to include progression-free survival; overall response rate; time to progression; and safety.

Lilly cited a subgroup of patients with an elevated baseline of alpha-fetoprotein (AFP) of ≥400 ng/mL that showed statistically significant OS improvement with Cyramza treatment. Median OS in this subgroup of patients was 7.8 months in the Cyramza arm compared to 4.2 months in the placebo arm.

The results were among REACH study analyses presented earlier this year at the Gastrointestinal Cancers Symposium. Lilly concluded that a greater reduction in the risk of death in patients with progressively higher baseline AFP values was promising enough to warrant further study.

As a result, Lilly said, it will soon begin enrollment in a new Phase III trial to evaluate the benefit of Cyramza treatment in advanced liver cancer patients with an elevated baseline AFP. The trial will be named REACH-2 (NCT02435433).

“We are encouraged by the efficacy seen overall in the REACH study, especially in specific subpopulations, and we hope to confirm those results with the new Cyramza Phase III trial,” Richard Gaynor, M.D., senior vice president of product development and medical affairs for Lilly Oncology, said in a statement.

He also noted that there are no approved therapies for second-line HCC in the United States, the European Union, or Japan.

REACH is a global, randomized, double-blind study that began in 2010 and has enrolled 565 patients in 27 countries. REACH compared Cyramza plus best supportive care to placebo and best supportive care as a second-line treatment in patients with hepatocellular carcinoma who have been previously treated with sorafenib in the first-line setting.

Safety data was consistent with results from previous single-agent Cyramza studies, as well as product safety information within the U.S. Prescribing Information for the drug. The most common clinical-grade adverse events occurring more frequently in patients on the Cyramza arm compared to the control arm were hypertension (12% vs. 4%), fatigue (5% vs. 2%), and malignant neoplasm progression (6% vs. 4%).

Cyramza’s safety profile in patients with elevated baseline AFP was consistent with that observed in the overall safety population, Lilly added.

Cyramza is a vascular endothelial growth factor receptor-2 (VEGFR-2) antagonist designed to work by binding and blocking activation of VEGF-2, and by binding VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D.

Cyramza is indicated in the United States for:

  • Advanced gastric or gastroesophageal junction adenocarcinoma—a form of cancer located in the region where the esophagus joins the stomach—with disease progression on or after prior chemotherapy containing fluoropyrimidine or platinum, alone or with paclitaxel.
  • Metastatic non-small cell lung cancer with disease progression on or after platinum-based chemotherapy, in combination with docetaxel.
  • Metastatic colorectal cancer with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine, in combination with Folfiri. This indication was approved in April.

Lilly took over development of Cyramza in 2008 when it acquired ImClone Systems.








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