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Cabometyx-Tecentriq Combination Produces 'Encouraging Clinical Activity' in Previously Treated Bladder Cancer
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At a median follow-up of 19.7 months, patients who received the combination achieved an objective response rate (the proportion of patients who had a complete or partial response to treatment) of 27%.
New data from the COSMIC-021 trial presented at the 2020 ASCO Virtual Scientific Program showed that the combination of Cabometyx (cabozantinib) and Tecentriq (atezolizumab) demonstrated promising objective responses in patients with urothelial carcinoma whose disease had progressed after receiving treatment with platinum-containing chemotherapy.
“Cabozantinib has shown promising activity in combinations with immune-checkpoint inhibitors in multiple tumor types, including recent results with a combination of cabozantinib and nivolumab (Opdivo) in the phase 3 CheckMate 9ER trial on first line renal cell carcinoma,” said Dr. Sumanta K. Pal, co-director of the Kidney Cancer Program at City of Hope in California, in a pre-recorded presentation of the data.
“Monotherapy with immune-checkpoint inhibitors, including the PD-L1-targeted antibody atezolizumab, is approved for patients with locally advanced or metastatic urothelial carcinoma with disease progression after platinum-containing chemotherapy.”
COSMIC-021 is a multi-center phase 1b study evaluating the combination of Cabometyx with Tecentriq in various solid tumors. Here, Pal presented results from a urothelial cancer expansion cohort of 30 patients.
At a median follow-up of 19.7 months, patients who received the combination achieved an objective response rate (the proportion of patients who had a complete or partial response to treatment) of 27%. Two patients achieved a complete response and six reached a partial response. More than half (53%) of the patients experienced a reduction in the size of their lesion; the disease control rate was 63%.
A median duration of response has not yet been reached; currently, the longest ongoing response is more than 15.6 months. Investigators observed 22 progression-free survival events (PFS), meaning the amount of time from the start of treatment until disease progression. The median PFS was 5.4 months.
“A combination of cabozantinib and atezolizumab demonstrated encouraging clinical activity in patients with urothelial carcinoma previously treated with platinum-containing chemotherapy, with an objective response rate of 27% and deep and durable responses,” Pal said.
“Additional cohorts evaluating the combination in urothelial carcinoma have been initiated in cisplatin-ineligible and cisplatin-eligible disease without prior systemic therapy, as well as urothelial carcinoma previously treated with checkpoint-inhibitor therapy.”
The COSMIC-021 trial is divided into two parts: a dose-escalation phase and an expansion-cohort phase.
Investigators determined that the optimal dose of Cabometyx is 40 milligrams (mg) per day when administered in combination with 1,200 mg of Tecentriq every three weeks.
The expansion cohort consists of 24 cohorts across 12 tumor types, including, but not limited to:
- urothelial carcinoma;
- renal cell carcinoma;
- non-small cell lung cancer;
- metastatic castration-resistant prostate cancer, and
- triple-negative breast cancer.
To be eligible for the urothelial carcinoma cohort, patients had to be diagnosed with inoperable locally advanced, metastatic, or recurrent disease that progressed on or after receiving treatment with a platinum-containing chemotherapy.
Ninety percent of the patients experienced a side effect associated with treatment. The most common side effects patients reported, which were not considered severe or serious, were weakness (37%); diarrhea (27%); and decreased appetite (23%).
More than half of the patients (56.3%) experienced a grade 3 or 4 side effect related to treatment, which is serious or severe. The most common occurrences included a sudden blockage in a lung artery (13%) and weakness (6.7%).
The investigators did not observe any treatment discontinuations as a result of the treatment-related side effects.
Pal noted that further research assessing the combination in urothelial carcinoma is ongoing.
“Additional cohorts evaluating the combination in urothelial carcinoma have been initiated in cisplatin-ineligible and cisplatin-eligible disease without prior systemic therapy, as well as urothelial carcinoma previously treated with checkpoint-inhibitor therapy,” he concluded.
A version of this story originally appeared on OncLive® as “Cabozantinib/Atezolizumab Combo Shows Promise in Previously Treated Urothelial Carcinoma”.
