Anti–PD-L1 monoclonal antibody benmelstobart plus anlotinib for the frontline treatment of advanced renal cell carcinoma (RCC), a type of kidney cancer, demonstrated improved clinical outcomes compared with Sutent (sunitinib), according to findings from the phase 3 ETER100 trial presented during the 2024 ESMO Congress.
Patients in the combination group (benmelstobart plus anlotinib; 264 patients) achieved a median progression-free survival (PFS; how long a person lives without their disease getting worse) of 18.96 months versus 9.76 months in the Sutent group (263 patients). The median overall survival (OS; the time from the start of treatment when a patient with cancer is still alive) was not estimable compared with NE, respectively. Of note, when median OS is not estimable in a clinical trial, it means that there was insufficient data for researchers to calculate this.
The respective overall response rates (ORRs; the percentage of people whose disease shrinks or disappears after treatment) were 71.6% versus 25.1%; 1.1% of patients in the combination group achieved a complete response.
“Based on our findings, we believe that benmelstobart in combination with anlotinib has the potential to become a new standard first-line treatment for advanced RCC,” Dr. Xinan Sheng, of Peking University Cancer Hospital and Institute in Beijing, China, said during the presentation. “At the [data cutoff] date, [findings from] the analysis showed a significant improvement in the combination group over the [Sutent] group. The combination treatment reduced the risk of progression [of disease] or death by 47% compared with [Sutent].”
Design of the ETER100 Study
ETER100 was a multicenter study that enrolled patients with locally advanced or metastatic clear cell RCC who did not undergo prior systemic antitumor therapy. To be eligible for the study, patients needed to be 18 to 80 years of age, have an ECOG performance status of 1 or less (1 being lightly active, 0 being fully active) and have at least 1 measurable lesion. Patients with prior exposure to any VEGFR-directed TKIs or immune checkpoint inhibitors were excluded.
Patients were randomly assigned to receive anlotinib plus benmelstobart or Sutent. Treatment in both groups continued until disease progression or intolerable toxicity.
The primary focus was PFS. The secondary focus included investigator (healthcare professional)-assessed PFS, OS, ORR, disease control rate, duration of response (the length of time a person's disease remains in remission after treatment) and safety.
Additional Findings from ETER100
Findings from a subgroup analysis showed that the PFS benefit observed with anlotinib plus benmelstobart versus Sutent was sustained across all subgroups. Patients with sarcomatoid differentiation (highly aggressive form of RCC) and those with liver metastasis experienced the greatest positive effects from the treatment.
In terms of safety, patients in the investigational and control groups both experienced any-grade treatment-emergent side effects at rates of 99.24%. Patients in both groups also had grade 3 (severe) or higher (life-threatening or death) treatment-emergent side effects (75% versus 74.62%), any-grade treatment-related side effects (98.11% versus 98.11%), grade 3 or higher treatment-related side effects (67.42% versus 65.91%) and serious side effects (38.64% versus 28.03%), respectively. Additionally, patients in the combination group experienced immune-related side effects (33.33%), grade 3 or higher immune-related side effects (9.47%) and immune-related reactions (4.92%).
One-hundred and thirty-eight patients in the combination group discontinued treatment due to disease progression (84 patients), side effects (12 patients), patient withdrawal (six patients), death (17 patients), lost to follow-up (three patients) and other reasons (16 patients). Among patients in the Sutent group, 209 discontinued treatments due to disease progression (142 patients), side effects (12 patients), patient withdrawal (21 patients), death (eight patients), lost to follow-up (one patient) and other reasons (25 patients).
“The addition of benmelstobart to anlotinib as a first-line treatment for [patients with] advanced RCC provided superior [results] compared with [Sutent],” Sheng said in conclusion. “The combination [of drugs] was generally well-tolerated, with a safety profile consistent with each agent.”
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