by Dr. C.H. Weaver M.D. updated 6/2020

Keytruda® (pembrolizumab) anti-PD-1 therapy in combination with Inlyta® (axitinib), a tyrosine kinase inhibitor (TKI) improved both overall survival (OS) and delayed the time to cancer progression compared to Sutent (sunitinib) when used in the first-line treatment of advanced or metastatic renal cell carcinoma (RCC).

Results from Phase 3 KEYNOTE-426 Study presented at the 2019 Genitourinary Cancers Symposium (ASCO GU) and published in the New England Journal of Medicine showed risk of progression or death reduced by 31 Percent and have led to recent FDA approval.(1)

Keytruda - Inlyta is the first combination regimen to significantly improve the response to treatment, overall survival, and progression-compared to Sutent. Benefit was seen across all subgroups of advanced renal cell cancer, including favorable, intermediate and poor risk groups, regardless of PD-L1 expression.

About Renal Cell Carcinoma

Each year in the United States, more than 61,000 people are diagnosed with kidney cancer. The most common type of kidney cancer is RCC, which starts in the lining of very small tubes (tubules) in the kidney. For people with advanced or metastatic RCC (cancer that has spread to other parts of the body), targeted therapies can play an important role in treatment. Approximately 20% to 30% of patients with RCC will have metastases at diagnosis and as many as 40% will demonstrate metastasis after treatment for earlier stage RCC. With a 5-year survival rate ranging from 5-10% for patients with advanced RCC, the overall prognosis for these patients is poor. (2,3,4)

About KEYNOTE-426

KEYNOTE-426 is a phase III clinical trial designed to evaluate the safety and effectiveness of Keytruda in combination with Inlyta as first-line treatment for advanced or metastatic RCC compared to Sutent. In the trial, 861 patients were randomly assigned to receive Keytruda 200 mg intravenously every three weeks plus Inlyta 5 mg orally twice daily for up to 24 months, or Sutent 50 mg orally once daily for four weeks followed by no treatment for two weeks, continuously.

About Keytruda

Keytruda® (pembrolizumab) belongs to a new class of medicines called PD-1 inhibitors that help the immune system recognize and attack cancer. PD-1 is a protein that inhibits certain types of immune responses. Drugs that block PD-1 may enhance the ability of the immune system to fight cancer. Keytruda® works by blocking PD-1. This treatment strategy has previously produced impressive results in melanoma and other cancer types.1

About Inlyta

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 renal cell carcinoma (RCC) after failure of one prior systemic therapy.

The US Food and Drug Administration initially approved Inlyta® (axitinib) for the treatment of advanced renal cell (kidney) cancer that has not responded to another drug based on a study in 723 patients with metastatic, clear-cell, renal cell cancer. All patients had experienced cancer progression after initial treatment that included Sutent® (sunitinib), Avastin® (bevacizumab), Torisel® (temsirolimus), or cytokine therapy. Study participants were assigned to treatment with either Inlyta or Nexavar® (sorafenib). Inlyta delayed the worsening of the cancer: progression-free survival was 6.7 months among patients treated with Inlyta and 4.7 months among patients treated with Nexavar.

Keynote 0426 Trial Results

According to a report at the ASCO20 Virtual Scientific Program KEYNOTE-426 continued to confirm Keytruda-Inlyta's benefit when compared with Sutent for treated of advanced RCC. (9)

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Now with a median follow-up period of 27 months the combination treatment was significantly associated with an improved 24-month overall survival rate (74% vs 66%) compared with Sutent.

Overall 38% of Keytruda-Inlyta treated patients survive without cancer progression compared to 27% for Sutent 2 years from treatment - the combination is significantly associated with a 29% decreased risk of cancer progression

Keytrude + Inlyta when directly compared to Sutent

  • Showed a reduction in the risk of progression of disease or death of 31 percent
  • Achieved a response to treatment of 59.3% compared to 35.7%
  • Complete response rate of 5.8%
  • Median duration of response was not reached in the Keytruda combination and is 15.2 months for Sutent

Learn More About the Treatment of Renal Cell Cancer...

Combining two precision cancer medicines for the treatment of RCC appears promising. The combination of an immune PD-1 checkpoint inhibitor with a TKI for patients with advanced RCC represents a new approach for the treatment of this disease. Recently another PD-1 inhibitor, Bavencio® when combined with Inlyta® was also reported to delay the time to cancer progression in previously untreated patients with advanced RCC.(7)


  2. National Cancer Institute: SEER Stat Fact Sheets: Kidney and renal pelvis. Available here. Accessed July 2018.
  3. Ljungberg B, Campbell S and Cho H. The Epidemiology of Renal Cell Carcinoma. Eur Urol. 2011;60:615-621.
  4. American Cancer Society. What is kidney cancer? Available here. Accessed July 2018.
  5. 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.
  6. World Cancer Research Fund International: Kidney cancer statistics. Available here
  7. Accessed July 2018.
  8. FDA News Release. FDA approves Inlyta to treat patients with a type of advanced kidney cancer. January 27, 2012.
  9. Plimack ER, Rini BI, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced renal cell carcinoma (RCC): Updated analysis of KEYNOTE-426. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 5001.