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The results of the phase 3 trial, according to one expert, support the use of Lenvima with Keytruda as a possible first-line treatment option for patients with advanced renal cell carcinoma.
Treatment with Lenvima (lenvatinib) plus Keytruda (pembrolizumab) resulted in significant improvements in overall survival (OS), progression-free survival (PFS) and objective response rates in patients with advanced renal cell carcinoma (RCC) who received the combination as their first treatment, compared to Sutent (sunitinib) alone.
The data, which were presented during the virtual 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium, also demonstrated that Lenvima plus Afinitor (everolimus) improved PFS (the time from treatment to disease progression or worsening) and objective response rates (the proportion of patients who had a complete or partial response to treatment) compared to Sutent alone in that patient population. However, the combination of Lenvima and Afinitor did not benefit OS when compared to Sutent.
Previously, single-agent Lenvima and Keytruda have been shown to be effective in treating RCC. The combination of Lenvima and Afinitor has also been shown to prolong PFS compared to single-agent Afinitor when administered after initial treatment has failed. And, as Dr. Robert J. Motzer noted during his presentation, results of a recent phase 1b/2 study of Lenvima plus Keytruda demonstrated anti-tumor activity in previously treated patients with RCC.
As a result, researchers aimed to assess the safety and efficacy of Lenvima plus Keytruda, as well as Lenvima plus Afinitor, versus Sutent alone as the first treatment option for patients with advanced RCC.
Motzer, the Kidney Cancer Section Head of the Genitourinary Oncology Service at Memorial Sloan Kettering Cancer Center in New York, presented results of the multi-center, open-label trial during the meeting.
The researchers enrolled 1,069 patients who were treatment-naive, had adequate organ function, had measurable disease and presented with advanced clear-cell RCC.
Patients were randomized to receive either 20 milligrams of Lenvima by mouth once a day plus 20 milligrams of Keytruda delivered via IV every three weeks (355 patients), 18 milligrams of Lenvima by mouth once a day plus 5 milligrams of Afinitor by mouth once a day (357 patients), or 50 milligrams of Sutent by mouth once a day for four weeks on and two weeks off (357 patients).
Measuring PFS was the main goal of the study. Other goals included assessing OS, objective response rates, safety and health-related quality of life.
Treatment with Lenvima plus Keytruda resulted in a median PFS of 23.9 months compared to 9.2 months with Sutent. Patients who received Lenvima plus Afinitor also reached a longer median PFS (14.7 months) than those who received Sutent (9.2 months).
None of the three treatment arms reached a median OS at the time of data cutoff in August 2020; however, Motzer noted the data indicated the OS benefit was best in the Lenvima plus Keytruda arm. Motzer continued to mention that there was no observed OS benefit in the Lenvima plus Afinitor treatment arm compared to Sutent alone.
The data also demonstrated that patients in both the Lenvima plus Keytruda arm and Lenvima plus Afinitor arm (71% and 53.5%, respectively) achieved a greater objective response rate than those in the Sutent arm (36.1%). Of note, Motzer mentioned the “high complete response rate” of 16.1% in the Lenvima plus Keytruda arm.
Patients in the Lenvima plus Keytruda arm also achieved the longest median duration of response to treatment at 25.8 months, compared to 16.6 months in the Lenvima plus Afinitor arm and 14.6 months in the Sutent arm.
Nearly all patients in each treatment arm – Lenvima plus Keytruda (96.9%), Lenvima plus Afinitor (97.7%) and Sutent (92.1%) – experienced any treatment-related side effects. Treatment with Lenvima plus Keytruda (67.3%) and Lenvima plus Afinitor (69.3%) were associated with more treatment-related side effect dose reductions than treatment with Sutent (49.7%). Of note, Motzer highlighted that the number of patients needing to have Lenvima discontinued in either treatment arm was 18.5% and 16.1%, respectively. Moreover, the discontinuation rate of both drugs in the Lenvima plus Keytruda arm was 9.7%.
Motzer noted the safety profiles of both combinations were consistent with each drugs’ known safety profile and were manageable as needed for dose modifications.
“These results support (Lenvima) plus (Keytruda) as a potential first-line treatment for patients with advanced RCC,” he concluded.
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