US-based pharmaceutical company Merck announced that the US Food and Drug Administration (FDA) has approved the combination of KEYTRUDA and LENVIMA to treat endometrial carcinoma.

KEYTRUDA is Merck’s anti-PD-1 therapy, while LENVIMA is the orally available kinase inhibitor discovered by Eisai.

The combination treatment is for patients with advanced endometrial carcinoma with disease progression after systemic therapy and is not candidates to curative surgery or radiation.

Eisai Oncology Business Group vice-president, chief medicine creation and chief discovery officer Takashi Owa said: “At least 75% of endometrial cancer cases are not microsatellite instability-high or mismatch repair deficient, and these women have been in need of new treatment options.

“We are excited for the advancement that today’s approval of the KEYTRUDA plus LENVIMA combination treatment represents for these women whose advanced endometrial carcinoma is not microsatellite instability-high or mismatch repair deficient, has progressed following prior systemic therapy and who are not candidates for curative surgery or radiation, and we look forward to the possibilities that our collaboration holds.”

FDA approval is based on the tumour response rate and durability of response

The FDA approval marks the first US approval for the combination of KEYTRUDA plus LENVIMA and the first time an anti-PD-1 therapy is approved in combination with a kinase inhibitor for advanced endometrial carcinoma in the US.

Merck has secured an accelerated approval reviewed under the FDA’s Real-Time Oncology Review (RTOR) pilot program, following submission on 17 June 2019.

The FDA approval is based on data from KEYNOTE-146/Study 111, a phase 2, multi-cohort, multicenter, open-label, single-arm trial that enrolled 108 patients with metastatic endometrial carcinoma that had progressed following at least one prior systemic therapy in any setting.

Using KEYTRUDA may cause Immune-mediated adverse reactions including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT).

In addition, the drug is also associated with causing severe or life-threatening infusion-related reactions, and may cause foetal harm when administered to a pregnant woman, based on its mechanism of action.

The use of KEYTRUDA should be kept on hold or discontinued based on the severity of the adverse reaction, and corticosteroids are administered if needed.

Use of LENVIMA may cause adverse reactions including hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, renal failure or impairment, proteinuria, diarrhea, fistula formation and gastrointestinal perforation, QT interval prolongation.

In addition, it may also hypocalcemia, reversible posterior leukoencephalopathy syndrome, hemorrhagic events, impairment of thyroid stimulating hormone suppression/thyroid dysfunction, and wound healing complications.

LENVIMA administration should be interrupted, reduced or discontinued based on the type and severity of the adverse reaction. It may cause damage to the foetus when administered to a pregnant woman.