by Dr. C.H. Weaver M.D. 2/2019
It is estimated there will be 73,820 individuals diagnosed with kidney cancer this year and 14,770 will succumb to their disease.1 Metastatic renal cell cancer currently has a 5-year survival rate of 12%.2
Checkpoint inhibitors are novel precision cancer immunotherapy drugs that helps to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD -L1 are proteins that inhibit certain types of immune responses, allowing cancer cells to evade an attack by the body’s immune cells. Checkpoint inhibitor drugs block the PD-1 pathway and enhance the ability of the immune system to fight cancer. Checkpoint inhibitors have improved the outcomes of many cancers including melanoma and lung cancer.
Results from the KEYNOTE-426 clinical trial show that first-line therapy with a combination of the PD-1 checkpoint inhibitor Keytruda (pembrolizumab) and the VEGF-targeted tyrosine kinase inhibitor Inlyta (axitinib) improve overall survival and delay cancer progression-free survival for patients with clear-cell metastatic renal cell carcinoma (mRCC), compared with the current standard of care, Sutent (sunitinib).
The US Food and Drug Administration (FDA) previously approved another checkpoint inhibitor Opdivo (nivolumab) combined with Yervoy as first-line, treatment for patients with advanced kidney cancer based on results from the CheckMate 214 clinical study which enrolled 1,100 patients with previously untreated advanced renal cell carcinoma. At 18 months after initiating treatment, 75% of patients treated with the Opdivo combination were still alive, compared with only 60% of those treated with Sutent. At a median follow-up of 25 months, the median overall survival for patients treated with the Opdivo combination had not been reached. For patients treated with sunitinib, it was 26 months.
Keytruda® is the first checkpoint inhibitor to have received FDA approval in the U.S for the treatment of cancer and Opdivo is the first to be approved for the treatment of advanced renal cell cancer. Bavencio (avelumab), another checkpoint inhibitor is currently being reviewed by the US FDA. Doctors will continue to evaluate the best way to use these and other checkpoint inhibitors for the management of renal cell carcinoma. There are several checkpoint inhibitor drugs available or in development.
- Keytruda® (pembrolizumab)
- Opdivo (nivolumab)
- Imfinzi (durvalumab)
- Tecentriq® (atezolizumab)
- Bavencio® (avelumab)
Inlyta is an oral targeted drug known as a small-molecule tyrosine kinase inhibitor. It works by blocking certain proteins that play a role in cancer growth. In the US, Inlyta is approved for the treatment of advanced RCC after failure of one prior systemic therapy. The developers of both Keytruda and Bavencio elected to combine their checkpoint inhibitor drugs with Inlyta in order to determine their effectiveness in the treatment of advanced RCC.
Results of Keynote 426: Keytruda + Inlyta
At a median follow-up of 12.8 months, a comparison of patients receiving Keytruda + Inlyta compared to Sutent in the treatment of advanced renal cell carcinoma demonstrated that;
· The combination therapy was associated with a 47% reduction in the risk of death compared with Sutent.
· The 12-month overall survival rate was 90% in the combination group vs 78% in the Sutent group.
· Combination patients lived a median of 15.1 months without disease progression vs. 11.1 months with Sutent.
· Serious treatment-related side effects were seen in 63% of people on the combination therapy compared to 58.% who received Sutent.
The initial results from the JAVELIN clinical study evaluating Bavencio® (avelumab) in combination with Inlyta® compared to Sutent® as initial therapy for patients with advanced renal cell carcinoma have also been released and the study shows a statistically significant improvement in progression-free survival (PFS) for all patients treated with the combination. Tull results of the clinical trial will be updated at a major medical meeting in the near future.
National Cancer Institute: SEER Stat Fact Sheets: Kidney and renal pelvis. Available from: . Accessed July 2018.
Ljungberg B, Campbell S and Cho H. The Epidemiology of Renal Cell Carcinoma. Eur Urol. 2011;60:615-621.
American Cancer Society. What is kidney cancer? Available from: . Accessed July 2018.
Escudier B, Porta C, Schmidinger M et al Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annal Oncol. 2014; 25(Suppl3):iii49-iii56.
World Cancer Research Fund International: Kidney cancer statistics. Available from: . Accessed July 2018.