Lilly Phase 3 REACH-2 Trial Data Shows Improvement in Overall Survival with CYRAMZA

Eli Lilly and Company announced that results from the global Phase 3 REACH-2 study of CYRAMZA (ramucirumab) as a single agent in the second-line treatment of people with AFP-High (alpha-fetoprotein ≥400 ng/mL) hepatocellular carcinoma (HCC) were published online in The Lancet Oncology. Data from REACH-2 are also being presented at the 2019 Gastrointestinal Cancers Symposium in San Francisco. HCC is also known as liver cancer, which is a leading cause of cancer-related death worldwide. In the U.S., liver cancer is one of the few major cancers with incidence rates that continue to rise every year and is the fastest rising cause of cancer death. REACH-2 showed a statistically significant improvement in the primary endpoint of overall survival (OS) as well as in the secondary endpoint of progression-free survival (PFS). The safety profile observed in the REACH-2 study was consistent with what has been previously observed for single-agent CYRAMZA in patients with HCC. Additionally, in a pooled analysis comprised of all AFP-High HCC patients across both the REACH-2 and REACH studies, CYRAMZA treatment also resulted in an improvement in median OS.

“AFP has been used as a prognostic factor for hepatocellular carcinoma for decades. Some studies have suggested that AFP-producing tumors have an aggressive phenotype and increased angiogenesis,” said Andrew X. Zhu, M.D., Director of Liver Cancer Research at Massachusetts General Hospital Cancer Center, Professor of Medicine at Harvard Medical School, and principal investigator of the REACH-2 and REACH trials. “These results not only further add to the body of evidence that poor prognosis tumors with elevated AFP may have a distinct biology, but also show a tailored treatment approach is feasible.” REACH-2, the first positive Phase 3 HCC trial in a biomarker-selected patient population, evaluated the benefit of CYRAMZA treatment in AFP-High HCC patients who were intolerant to, or had disease progression while on or following treatment with, sorafenib. Approximately half of all advanced HCC patients are AFP-High, and these patients are among those with the poorest prognosis relative to the general HCC patient population.

On the primary endpoint of OS, treatment with CYRAMZA significantly improved the OS of patients compared to placebo (HR 0.71; 95 percent CI, 0.53-0.95; P=0.02). The median OS was 8.5 months with CYRAMZA (95 percent CI, 7.0-10.6), compared to 7.3 months with placebo (95 percent CI, 5.4-9.1). On the secondary endpoint of PFS, median PFS was significantly improved with CYRAMZA (2.8 months [95 percent CI, 2.8-4.1] vs. 1.6 months for placebo [95 percent CI, 1.5-2.7]) (HR 0.45; 95 percent CI, 0.34-0.60; P<0.0001). Objective response rate (ORR) was numerically higher with CYRAMZA compared to placebo (4.6 percent vs. 1.1 percent; P=0.1697). Disease control rate (ORR + stable disease) was higher with CYRAMZA than with placebo (59.9 percent vs. 38.9 percent). In a pooled analysis of AFP-High patients (n=542) from REACH-2 and REACH, which provided a larger data set to assess outcomes in this particular patient population, CYRAMZA improved OS compared to placebo (HR 0.69; 95 percent CI, 0.57-0.84; P=0.0002), and an improvement of 3.1 months in median OS was observed (8.1 and 5.0 months with CYRAMZA and placebo, respectively). The HR for OS across all pre-specified pooled subgroup analyses favored the CYRAMZA treatment arm. PFS, ORR and disease control rate were consistent with those in REACH and REACH-2, and supported the pooled OS result.

“Demonstrating a significant improvement in survival for this group of patients with advanced liver cancer and elevated AFP is particularly exciting as these patients have the poorest prognosis – with an expected survival of only a few months following first-line treatment if they don’t go onto a second-line therapy. Treatment options are still limited in second-line liver cancer, and CYRAMZA is the first treatment specifically evaluated in this biomarker-selected population of liver cancer patients,” said Maura Dickler, M.D., vice president, late phase development, Lilly Oncology. “The published results of REACH-2 demonstrate the potential for CYRAMZA to make an impact on the treatment of people with this aggressive cancer, which is encouraging for healthcare providers and the patient community.” The safety profile observed in the REACH-2 study was consistent with what has been previously observed for single-agent CYRAMZA in patients with HCC. The Grade ≥3 adverse events occurring at a rate of five percent or greater in the CYRAMZA arm were hypertension and hyponatremia (low sodium). These data were first presented at the 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO) and 2018 World Congress on Gastrointestinal Cancer. Lilly has made regulatory submissions in the U.S., European Union and Japan based on the REACH-2 results. CYRAMZA is not yet approved for the HCC indication. – Medical Buyer Bureau