Patients with locally advanced or metastatic renal cell carcinoma who express the PD-L1 protein benefit more from the combination of Tecentriq (atezolizumab) plus Avastin (bevacizumab) than from treatment with Tecentriq alone or from Sutent (sunitinib), according to data from a Phase 2 trial.
Results from the Genentech trial were presented at the 2017 Genitourinary Cancers Symposium Feb. 16-18 in Orlando, Florida.
Renal cell carcinoma, the most common type of kidney cancer, forms in the small tubes in the kidneys. The American Cancer Society estimates that about 63,990 people will be diagnosed with kidney cancer in the U.S. in 2017 alone, and 14,400 will die from the disease.
The IMmotion150 Phase 2 trial (NCT01984242) is a global, multi-center, open-label, randomized study designed to assess the safety and effectiveness of Tecentriq in combination with Avastin (arm A), Tecentriq alone (arm B), or Sutent alone (arm C) in 305 patients with locally advanced or metastatic renal cell carcinoma who had not received any prior therapy.
Patients included in arm A received intravenous Tecentriq (1,200 mg) plus Avastin (15 mg) every three weeks in six-week cycles until disease progression or unacceptable toxicity. Those in arm B received Tecentriq as a monotherapy. And participants in arm C received oral Sutent (50 mg) daily for four weeks plus two weeks rest in six-week cycles, also until disease progression or unacceptable toxicity.
The study was designed so that patients in arms B and C who had disease progression would crossover to arm A and start receiving the combo therapy.
The study’s primary endpoints were progression-free survival in the intent-to-treat population (an analysis that is performed based on the initial treatment assignment and not on the treatment eventually received) and in the PD-L1 selected (IC1/2/3) subgroup. Secondary endpoints included overall response rate, duration of response, and safety.
Results showed that patients expressing the PD-L1 protein in their tumor-infiltrating immune cells had a 36 percent lower risk of their disease progressing when given Tecentriq plus Avastin, compared to Sutent alone. Patients in this arm had a median progression-free survival that nearly doubled that seen in the Sutent group (14.7 months vs. 7.8 months).
In the intent-to-treat analysis, however, no progression-free survival benefit was observed in the combo arm.
After a median of 20.7 months of follow-up, median duration of response had not been reached in any of the treatment arms.
The researchers noted that the safety profiles of the combo therapy was consistent to those observed in prior studies assessing each drug alone.
“These Phase 2 results support the scientific rationale for potentially combining Tecentriq and Avastin in people with this type of kidney cancer,” Sandra Horning, MD, chief medical officer and head of Global Product Development for Genentech, said in a news release. “There is a significant need for new treatment options for people living with advanced RCC, a disease where currently only about one in 10 people are alive beyond five years following diagnosis.”
Genentech is currently evaluating this combination vs. Sutent in a Phase 3 trial for the same indication (IMmotion151; NCT02420821) to further validate their findings.