NEW YORK (Reuters Health) – The combination of the multikinase inhibitor Lenvatinib and the anti-PD-1 antibody Pembrolizumab has “encouraging” antitumor activity and manageable side effects and could be an option. selected after immune checkpoint inhibitor therapy (Immune-checkpoint inhibitor: ICI) in studies reporting that patients with metastatic renal cell carcinoma (Renal-cell carcinoma: RCC).

Despite advances in first-line treatment of metastatic RCC, there is still an “unmet need” for options to address disease progression during or after ICI therapy, says Dr. -Han Lee of Memorial Sloan Kettering Cancer Center, in New York City, and colleagues write in The Lancet Oncology.

Pembrolizumab and Lenvatinib are acting as monotherapy in RCC. Phase 1b/2 111/KEYNOTE-146 study investigators tested this combination in 145 patients with metastatic RCC. Two patients with obvious non-cellular RCC were excluded from the efficacy analysis but included in the safety analysis.

The effective population included 22 treatment-nave patients, 17 patients previously treated with at least one line of therapy but no anti-PD-1 or anti-PD-L1 ICI, and 104 patients. ICI-treated patients (previously treated with anti-PD-1 or anti-PD-L1 ICI).

The regimen consisted of oral Lenvatinib 20 mg once daily plus Pembrolizumab 200 mg intravenously every three weeks. Patients continued treatment until their disease progressed, unacceptable drug toxicity developed, or the patient’s consent changed. The mean follow-up time was 19.8 months.

“Investigator-assessed objective response rates at 24 weeks per irRECIST were high in all three patient groups,” the researchers report.

Sixteen of 22 (73%) untreated patients had an objective response at week 24, as did 7 of 17 (41%) previously treated ICI-free patients, and 58 of 104 (56%) patients had pre-ICI treatment.

Of the 145 patients, 82 (57%) had Grade 3 treatment-related adverse events and 10 (7%) had Grade 4 treatment-related adverse events.

Hypertension was the most common Grade 3 treatment-related adverse event occurring in 30 patients (21%). Serious treatment-related adverse events occurred in 36 (25%) of patients, and there were three treatment-related deaths (upper gastrointestinal bleeding, sudden death, and pneumonia).

“To our knowledge, this is the largest study to date with TKI plus ICI in the treatment of metastatic renal cell carcinoma after disease progression with prior ICI therapy (ie, anti-renal carcinoma). -PD-1 or anti-PD-L1). Notably, the safety impact of the combination matched the safety impact of each drug,” the team wrote.

Lenvatinib in combination with pembrolizumab could be “a potential future standard of care treatment for patients with metastatic clear-cell RCC after disease progression with ICI therapy,” they said.

This combination is being studied further in phase 3 trials involving patients with various tumor types, including one in renal cell carcinoma. progression or metastasis”.

Refer: https://bit.ly/3qsvAbx The Lancet Oncology, online June 15, 2021.

Source: https://www.medscape.com/viewarticle/954223

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Translator: ToanTran.