A Combination of Immunotherapy and a Smart Drug Receives FDA Approval for the First Time in Cancer Treatment

Kidney cancerfirst-line treatment with the immunotherapy pembrolizumab (Keytruda) plus the tyrosine kinase inhibitor axitinib (Inlyta), on 19 April 2019, received FDA approval.

This is also the first FDA approval of a combination of immunotherapy and a smart cancer drug.

The approval was based on a randomized, multicenter, open-label clinical trial in previously untreated advanced kidney cancer involving 861 patients, KEYNOTE ‑ 426. Patients were enrolled regardless of tumor PD-L1 positivity and randomly assigned to two groups:

• In the experimental arm, every 3 weeks intravenous pembrolizumab at 200 mg, and 2 times daily oral axitinib at 5 mg,
• In the control arm, oral sunitinib once daily at 50 mg (4 weeks of treatment followed by a 2-week break).

Treatment continued until disease progression or unacceptable side effects. Immunotherapy with pembrolizumab was given for up to 24 months.

The main efficacy measures were overall survival and progression-free survival.

Study results

• Pembrolizumab plus axitinib was found to reduce the risk of death by %47 compared with sunitinib, the previous standard treatment for advanced kidney cancer.
• Although death was reported in % 18 of patients, median overall survival was not reached in either arm.
• The 12-month overall survival rate was %90 in the pembrolizumab plus axitinib arm, compared with %78 among patients treated with sunitinib.
• Patients receiving pembrolizumab plus axitinib had a %31 lower risk of cancer progression than those receiving standard treatment.
• The study’s most noteworthy result was median progression-free survival of 15.1 months with pembrolizumab plus axitinib versus 11.1 months in patients receiving sunitinib.

Severe (grade 3 or 4) hepatotoxicity (liver damage) occurred in % 20 of patients. Hepatotoxicity led to permanent discontinuation of pembrolizumab or axitinib in %13. In patients receiving pembrolizumab plus axitinib, the most common effects occurring in %20 or more were side effects such as diarrhea, fatigue / weakness, hypertension, hypothyroidism, decreased appetite, hepatotoxicity, palmar-plantar erythrodysesthesia, nausea, stomatitis / mucosal inflammation, dysphonia, rash, cough and constipation.

For first-line treatment of advanced kidney cancer, the recommended pembrolizumab dose is every 3 weeks intravenously at 200 mg, with axitinib twice daily at 5 mg.

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Below, you can see approved treatments for kidney cancer, median survival times and side-effect comparisons:

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