NEW YORK (TheStreet) — In 2005, U.S. regulators approved the first targeted drug to treat renal cell carcinoma, the most common form of kidney cancer. Ten years later, doctors treating kidney cancer patients have seven targeted drugs at their disposal, all approved on data showing an ability to significantly delay growth of tumors. The demonstration of a clinically meaningful survival benefit, however, has proven elusive.
That’s now changed with newly presented data for Opdivo, the immune system-boosting drug from Bristol-Myers Squibb (BMY – Get Report) . In a phase III study of previously treated kidney cancer patients, Opdivo achieved a median overall survival of 25 months, or more than five months longer than Afinitor, a current standard of care in this patient population sold by Novartis (NVS – Get Report) .
In a separate phase III study involving similar, previously treated kidney cancer patients, Exelixis’ (EXEL) Cometriq reduced the risk of tumor progression or death by 42% compared to Afinitor. An interim analysis of overall survival showed a 33% lower risk of death favoring Cometriq over Afinitor but the data are still immature and therefore did not yet reach statistical significance.
Both studies were published Friday night in the New England Journal of Medicine and will be presented formally at the European Cancer Congress on Saturday.
Based on these positive data, Bristol and Exelixis are both likely to secure new approvals next year for Opdivo and Cometriq to treat second-line kidney cancer patients. Which drug grabs a larger share of patients? Investors will be probing kidney cancer doctors at this weekend’s meeting to see which drug they prefer.
Dr. David Quinn of the Norris Comprehensive Cancer Center at the University of Southern California, believes Opdivo has the edge over Cometriq. In a NEJM editorial accompanying the publication of the two studies, Quinn says the benefit of both drugs for kidney cancer patients is "unequivocal" but then he adds:
Given the overall survival advantage it confers and its relatively good side-effect profile, nivolumab [Opdivo] is the choice for patients who have disease progression while they are receiving VEGF-targeted therapy. Cabozantinib [Cometriq] is a salvage treatment for patients whose tumors progress during VEGF therapy, however, without a significant overall survival benefit and with significant side effects… it will not precede nivolumab in the therapeutic sequence.
Opdivo belongs to the class of cancer immunotherapies known as checkpoint inhibitors, which work by blocking the interaction between PD-L1, a protein found on the surface of tumor cells, and PD-1, a receptor found on immune cells. Blocking the PD-1/PD-L1 connection allows a patient’s immune system to recognize and kill cancer cells. [Merck’s (MRK – Get Report) Keytruda is also a checkpoint inhibitor.]
In Bristol’s phase III study known as CheckMate-025, patients with kidney cancer no longer responding to front-line therapy were randomized to receive an injection of Opdivo every two weeks or a daily dose of oral Afinitor. The study was stopped early after an analysis showed Opdivo reduced the risk of death by 27% compared to Afinitor. At the median, overall survival of Opdivo patients was 25 months compared to 19.6 months for Afinitor patients.
In some cancer, checkpoint inhibitors are more effective against tumors which express higher levels of the PD-L1 protein. That wasn’t observed in the CheckMate-025 study. The Opdivo survival benefit was statistically significant regardless of the level of PD-L1 expression found in the kidney cancer tumors. However, three-quarters of the kidney cancer patients enrolled into the study had low levels of PD-L1 expression, yet their survival trended higher than the quarter of patients with higher levels of PD-L1.
In the study, patients treated with Opdivo also reported an overall response rate of 25% compared to 5% for Afinitor. The median duration of response to Opdivo lasted 12 months. Opdivo was associated with a lower incidence of serious adverse events (19%) compared to Afinitor (37%.)
Like in Bristol’s study, Exelixis enrolled second-line kidney cancer patients into its phase III study dubbed METEOR and randomized them to treatment with a daily dose of oral Cometriq or a daily oral dose of Afinitor. Cometriq demonstrated a 42% reduction in the risk of disease progression or death compared to Afinitor. At the median, progression-free survival was 7.4 months for Cometriq against 3.8 months for Afinitor.
A survival benefit trended in favor of Cometriq but was not statistically significant. The response rate attributable to Cometriq was 21% compared to 5% for Afinitor. while the incidence rate of serious adverse events was higher with Cometriq (68%) versus Afinitor (58%.)
Exelixis disclosed partial results from the METEOR study last July.
Renal cell carcinoma is the most common form of kidney cancer, with more than 330,00 cases diagnosed and more than 140,000 deaths worldwide each year. Pfizer’s (PFE – Get Report) Sutent is the most commonly used therapy for newly diagnosed kidney cancer patients. If approved, Opdivo and Cometriq would be used in patients who no longer respond to Sutent or some other targeted therapy.
Cometriq is already approved for a rare form of thyroid cancer. Opdivo is approved to treat skin cancer and lung cancer.
Adam Feuerstein writes regularly for TheStreet. In keeping with company editorial policy, he doesn’t own or short individual stocks, although he owns stock in TheStreet. He also doesn’t invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback; click here to send him an email.
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