Good news for patients with metastatic renal cell carcinoma20 Jul 2015
A clinical trial in metastatic renal cell carcinoma (RCC) ended early after an interim analysis showed a significant survival advantage with the immunotherapeutic agent nivolumab (Opdivo) versus everolimus (Afinitor), according to trial sponsor Bristol-Myers Squibb.
The company provided few details beyond the fact that an independent data monitoring committee had concluded that the CheckMate-025 phase 3 trial had met the primary endpoint of overall survival advantage and should not continue.
Almost simultaneously, sponsors of another phase 3 trial in metastatic RCC reported that treatment with the tyrosine kinase inhibitor cabozantinib (Cometriq) reduced the risk of progression or death by 42% as compared with everolimus. A preliminary analysis of overall survival showed a statistically significant 33% decrease in the hazard with cabozantinib, according to a statement from study sponsor Exelixis.
Immunotherapy’s mechanism of action
CheckMate-025 involved 821 patients with previously treated advanced or metastatic RCC. They were randomized to open-label nivolumab or everolimus and followed until progression, death, or unacceptable toxicity.
An immune checkpoint inhibitor, nivolumab targets the programmed death-1 (PD-1) receptor on activated T-cells to prevent activation of PD-1 ligand (PD-L1). The activity stimulates the immune system's response to cancer cells, which have turned off the response by abnormally perpetuating a normal checkpoint or braking effect on the immune system.
Nivolumab received FDA approval in 2014 for treatment of metastatic melanoma. A few months later, the FDA expanded the drug's indications to include advanced squamous non-small cell lung cancer. The agent is being evaluated in wide-ranging clinical development program that spans multiple tumor types.
Results of the second phase 3 trial
Exelixis officials reported the outcome of the METEOR study, a randomized, phase 3 trial involving 658 patients with previously treated RCC. They were randomized to cabozantinib or everolimus and continued treatment until progression, death, or unacceptable toxicity. The trial had a primary endpoint of progression-free survival (PFS).
The scientists reported that:
- The primary analysis showed that the cabozantinib arm had a hazard ratio of 0.58 for progression or death versus the everolimus arm.
- The preliminary survival analysis showed that the cabozantinib arm had a hazard ratio of 0.67 as compared with the everolimus group.
The survival follow-up will continue until 408 deaths have occurred.
“Preliminary but encouraging data on overall survival”
The METEOR results suggest that switching patients to a different TKI after progression is a reasonable strategy, said Toni Choueiri, MD, of Dana-Farber Cancer Institute in Boston, principal investigator of the METEOR trial.
"The data on overall survival also are very encouraging," added Choueiri. "The survival data are preliminary, but they show a strong trend in favor of cabozantinib. Discontinuation because of adverse events was low and similar in both treatment groups, so that is encouraging."
The limited information on the CheckMate-025 results makes them difficult to interpret, but the fact that the trial ended early because of a significant survival benefit is encouraging, he said.
Regardless of what the detailed information shows, the results of the two trials are good news for patients with metastatic RCC and for their physicians, as limited clinical progress has occurred in the field since 2006, when the first-generation TKI sunitinib (Sutent) received FDA approval, he added.Source: MedPage Today