The immunotherapy drug Opdivo (nivolumab) prolonged survival in patients with advanced renal cell carcinoma more effectively than a comparator drug, Afinitor (everolimus), in a recent phase 3 study.
The immunotherapy drug Opdivo (nivolumab) prolonged survival in patients with advanced renal cell carcinoma (RCC) more effectively than a comparator drug, Afinitor (everolimus), in a recent phase 3 study.
In fact, the trial, known as CheckMate-025, was stopped early because of the favorable results.
Due to these findings, Bristol-Myers Squibb (BMS), the manufacturer of Opdivo, announced that eligible patients in the Afinitor arm can cross over to receive Opdivo in an open-label extension of the study.
“The results of CheckMate-025 mark the first time an immuno-oncology agent has demonstrated a survival advantage in advanced renal cell carcinoma, a patient group that currently has limited treatment options,” Michael Giordano, senior vice president, Head of Development, Oncology, BMS, said in a statement.
Opdivo works by stopping the activity of PD-1, a protein that sits on some immune cells. Uninhibited, PD-1 helps cancer cells hide from the body’s immune system; blocking its activity allows the body to recognize and fight the cells. Afinitor blocks a different action, that of the protein kinase, or enzyme, mTOR. This quiets messages that tell cancer cells and tumor blood vessels to develop.
CheckMate-025 randomized 821 previously treated patients with advanced or metastatic clear-cell RCC to 3 mg/kg of intravenous Opdivo every two weeks or 10 mg of oral Afinitor daily until progression or unacceptable toxicity. Prior treatment with one or two antiangiogenic treatment regimens for advanced or metastatic disease (therapies that stop the growth of blood vessels to tumors) was required, along with evidence of disease progression within six months of enrollment. Overall survival (OS) was the primary endpoint, with secondary outcome measures including objective response rate (ORR) and progression-free survival (PFS).
Previously published phase 2 data demonstrated clinical activity for Opdivo with acceptable toxicity in 168 patients with metastatic RCC (mRCC) who had previously received anti-VEGF (antiangiogenic) therapy.1 Seventy percent of patients in the study (n = 118) had received more than one prior systemic regimen.
In a blinded 1:1:1 randomization, patients received either 0.3 (n = 60), 2.0 (n = 54) or 10 mg/kg (n = 54) of intravenous Opdivo once every three weeks. PFS was the primary outcome measure, with secondary endpoints including ORR and OS.
In order of increasing dosage, median PFS was 2.7, 4.0 and 4.2 months, respectively, with ORRs of 20 percent, 22 percent and 20 percent. In the three treatment arms, median OS was 18.2 months, 25.5 months and 24.7 months, respectively.
Fatigue was the most frequently reported side effect, with rates of 24 percent, 22 percent and 35 percent in the 0.3-, 2.0- and 10-mg/kg cohorts, respectively. Severe treatment-related side effects were reported for 11 percent of patients (n =19) in the overall study population.
“Through our Opdivo clinical development program, we aim to redefine treatment expectations for patients with advanced RCC by providing improved survival,” Giordano said.
Results from another successful trial in RCC were also released this week. In the phase 3 METEOR trial, the multikinase inhibitor Cometriq (cabozantinib), which targets multiple enzymes involved in cancer growth, improved PFS and OS versus Afinitor in the second-line setting for the treatment of patients with mRCC. Exelixis, the company developing Cometriq, plans to file for regulatory approval of the drug in this setting in early 2016.
Opdivo was initially approved in December 2014 for patients with unresectable or metastatic melanoma following treatment with Yervoy (ipilimumab) or an inhibitor of the mutated BRAF protein, which contributes to cancer growth. In March 2015, Opdivo was approved for the treatment of patients with advanced squamous non—small cell lung cancer who have progressed on or after platinum-based chemotherapy.
The FDA is currently reviewing an application for Opdivo in combination with Yervoy in the frontline setting for patients with advanced melanoma. A decision is expected by September 30 of this year.