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Everolimus prolongs PFS for lung, GI neuroendocrine tumors
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Everolimus conferred a statistically significant and clinically meaningful PFS benefit with an acceptable safety profile in patients with advanced, progressive neuroendocrine tumors of the lung or gastrointestinal region, according to phase 3 trial results presented at European Society of Medical Oncology’s European Cancer Congress.
Everolimus (Afinitor, Novartis) is a mammalian target of rapamycin inhibitor currently approved for the treatment of advanced pancreatic neuroendocrine tumors (NETs). However, patients with advanced, nonfunctional NETs of the lung or GI region represent an unmet medical need with very few available treatment options, according to study background.
“This is the first randomized clinical trial to show any benefit in lung NETs,” James C. Yao, MD, professor in the department of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center, told HemOnc Today. “There is no other treatment available for those patients. Outside the pancreatic area, there is really no approved treatment that shows any benefit for progressive NETs.”
Yao and colleagues conducted the double blind, controlled phase 3 RADIANT-4 trial to determine the safety and efficacy of everolimus in patients with advanced lung or GI NETs. They randomly assigned 302 patients (median age, 63 years; 53% women) daily everolimus (10 mg; n = 205) or placebo (n = 97) along with best supportive care.
Patient stratification factors included tumor origin, WHO performance status and prior somatostatin analogue (SSA) treatment. Both arms had similar rates of prior SSA treatment (53% vs. 56%), chemotherapy receipt (26% vs. 24%) and radiotherapy (22% vs. 20%).
PFS served as the primary endpoint. Secondary endpoints included OS, objective response rate (ORR), disease control rate (DCR) and safety.
According to a central review assessment, patients assigned everolimus achieved a median PFS of 11 months (95% CI, 9.2-13.3), which represented a significant improvement compared with the 3.9-month median PFS (95% CI, 3.6-7.4) in the placebo arm (HR = 0.48; 95% CI, 0.35-0.67).
The researchers reached a similar PFS assessment (14 months vs. 5.5 months; HR = 0.39; 95% CI, 0.28-0.54).
Four patients assigned everolimus and one patient assigned placebo achieved a partial response. The everolimus arm also had a higher DCR (82% vs. 65%).
Nine percent of the everolimus arm had progressive disease as best outcome, compared with 27% of the placebo arm. Tumor response was unknown in the remaining patients.
The researchers conducted an interim OS analysis, which showed an HR of 0.64 (95% CI, 0.4-1.05), which favored everolimus but did not reach statistical significance.
The most frequent grade 3 or grade 4 adverse events in the everolimus vs. placebo arms included diarrhea (9% vs. 2%), stomatitis (7% vs. 0%), abdominal pain (5% both arms) and anemia (5% vs. 2%).
“Further analyses are planned,” Yao said. “We have collected quality-of-life data. Also, our interim OS analysis shows a trend toward OS benefit in addition to PFS benefit. Global regulatory filings are forthcoming, including in the U.S.” – by Cameron Kelsall
For more information:
James C. Yao, MD, can be reached at The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030; email: jyao@mdanderson.org.
Reference:
Yao J, et al. Abstract 5LBA. Presented at: European Cancer Congress; September 25-29, 2015; Vienna.
Disclosure: Yao reports consultant roles with Ipsen, Lexicon and Novartis, as well as institutional research funding from Novartis. Please see the abstract for a list of all other researchers’ relevant financial disclosures.