a new review finds. Based on initial data, all appear to show advantages over the standard first-line treatment with the older targeted-therapy drug sunitinib.
However, the review, published in the International Journal of Urology, cautions that uncertainty remains because of the “absence of long-term prognostic as well as safety data regarding these combination therapies.”
The review, led by Ken-ichi Harada MD, PhD, of Kobe (Japan) University, notes that the introduction of targeted therapies and immuno-oncology drugs over the last 2 decades has revolutionized the treatment of advanced renal cell carcinoma. Multiple combination therapies based on immuno-oncology drugs are now recommended by treatment guidelines.
However, the lack of head-to-head data means that “it is still challenging for physicians to make the best decision on first-line therapy,” the authors wrote.
In the review, the authors recapped the evidence regarding several combination therapies:
- Ipilimumab plus nivolumab, a combination of two monoclonal antibodies, has shown higher overall survival than sunitinib in multiple studies. Treatment-related adverse events are common, however, with one trial reporting that they led 69% of patients to discontinue treatment. Even so, “ipilimumab plus nivolumab therapy continues to demonstrate durable efficacy benefits over sunitinib in advanced renal cell carcinoma patients classified into intermediate or poor risk group after long-term follow-up.”
- Avelumab, a monoclonal antibody, plus the tyrosine kinase inhibitor (TKI) axitinib has not shown better overall survival rates versus sunitinib in a single trial, although there are signs of better progression-free survival. “Accordingly, avelumab plus axitinib is either not or discreetly recommended as a standard first-line therapy for advanced renal cell carcinoma patients by major clinical guidelines.”
- Pembrolizumab, a monoclonal antibody, plus axitinib has shown better progression-free survival and overall survival than sunitinib in a single trial. “Accordingly, pembrolizumab plus axitinib could be expected to have a powerful impact on favorable long-term cancer control with less frequent occurrence of severe adverse events, considering almost equivalent landmark overall survival to ipilimumab plus nivolumab.”
- Nivolumab plus cabozantinib, a TKI, beat sunitinib in a single trial in terms of progression-free survival and overall survival. “Nivolumab plus cabozantinib could be regarded as an efficacious therapeutic option for untreated advanced renal cell carcinoma patients with manageable safety.”
- Pembrolizumab plus lenvatinib, a TKI, showed better overall survival versus sunitinib in a single trial.
“These findings suggest that pembrolizumab plus lenvatinib could provide marked benefits with regard to cancer control in treatment-naive advanced renal cell carcinoma patients, and that caution should be exercised regarding the safety profile, considering the initial introduction of lenvatinib in the field of urological malignancies,” the authors wrote.
When compared against each other, most of these treatments appear to perform similarly, the authors wrote. With the exception of avelumab plus axitinib, all “showed almost similar advantages for the improvement of overall survival compared with sunitinib, judging from hazard ratios, and all five immuno-oncology drug-based combination therapies, particularly pembrolizumab plus lenvatinib, significantly prolonged progression-free survival, compared with sunitinib.”
No study funding was reported. The authors report various disclosures including relationships to Novartis, Pfizer, Ono, Takeda, MSD, Merck, and Bristol-Myers Squibb.