The Lynx Group

Cabozantinib plus Atezolizumab Combination Shows Meaningful Activity in Metastatic Prostate Cancer

August 2020, Vol 11, Special Issue: Payers' Perspectives in Oncology

The combination of cabozantinib (Cabometyx), a kinase inhibitor, and atezolizumab (Tecentriq), a PD-L1 inhibitor, achieved clinically meaningful activity in patients with metastatic castration-resistant prostate cancer (CRPC), including those with high-risk clinical features, according to the results of the phase 1b COSMIC-021 trial presented at the ASCO 2020 virtual annual meeting.

“The combination of cabozantinib and atezolizumab demonstrated a tolerable safety profile and clinically meaningful activity in men with metastatic CRPC,” said lead investigator Neeraj Agarwal, MD, MBBS, Director, Genitourinary Oncology Program, Huntsman Cancer Institute, University of Utah, Salt Lake City.

“The combination treatment was associated with an increase in the number of activated cytotoxic T-cells with concomitant decrease in immunosuppressive cells in peripheral blood,” Dr Agarwal noted. “Preliminary data do not suggest an association between PD-L1 expression and antitumor activity.”

The cohort with metastatic CRPC “is being further expanded, and cohorts evaluating the contribution of cabozantinib and atezolizumab have been initiated. Further evaluation of cabozantinib and atezolizumab in metastatic CRPC in a phase 3 trial is planned,” he added.

COSMIC-021 Study

The multicenter, open-label, phase 1b COSMIC-021 clinical trial is evaluating the combination of atezolizumab and cabozantinib in patients with locally advanced or metastatic solid tumors. At the ASCO 2020 virtual meeting, Dr Agarwal reported data on the first 44 patients enrolled in the metastatic CRPC cohort. Previous treatment with docetaxel was allowed for patients with hormone-sensitive disease.

A total of 25 (57%) patients had a Gleason score of ≥8 at diagnosis. Moreover, 12 (27%) patients received previous treatment with docetaxel for metastatic castration-sensitive disease, and all 44 patients had received previous novel hormonal therapy.

In the 44 patients with metastatic CRPC who received the combination of cabozantinib and atezolizumab, the overall response rate (ORR) was 32%, with 3 complete responses and 11 partial responses. A total of 21 patients had stable disease, 8 patients had progressive disease, and the data were unavailable for 1 patient. The disease control rate was 80%.

In a subgroup of 36 patients with high-risk features, including visceral metastases and/or extrapelvic lymph node metastases, the ORR was 33%.

The median time to response was 1.6 months (range, 1-7 months), and the median duration of response was 8.3 months (range, 2.8-12.5+ months).

The median follow-up was 15.8 months (range, 9-23 months). A total of 36 (82%) patients had high-risk metastatic CRPC. In addition, 15 (34%) patients had visceral metastases and 27 (61%) patients had extrapelvic lymph node metastases.

A total of 25 (57%) patients had a Gleason score of ≥8 at diagnosis. Moreover, 12 (27%) patients received previous treatment with docetaxel for metastatic castration-sensitive disease, and all 44 patients had received previous novel hormonal therapy.

Cabozantinib was given orally at 40 mg once daily, and intravenous atezolizumab was given at 1200 mg every 3 weeks.

Adverse Events

Grade 3 or 4 adverse events were reported in 59% of patients. The treatment-related grade 3 or 4 adverse events that occurred in at least 5% of patients included fatigue (7%), diarrhea (7%), and hyponatremia (7%).

Immune-related grade 3 or 4 adverse events occurred in 4 patients, and adverse events led to dose reductions of cabozantinib in 19 patients. Treatment discontinuation that was unrelated to the study drugs was reported in 4 patients. There was 1 treatment-related grade 5 adverse event of dehydration.

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