Triplet Regimen Bests Single-Agent Cabometyx in Soft Tissue Sarcoma

The average progression-free survival for the three-drug group was 5.4 months, compared to 3.8 months in the Cabometyx-only arm.

Combining Cabometyx (cabozantinib) with the immunotherapy agents Opdivo (nivolumab) and Yervoy (ipilimumab) improved disease-control rate and progression-free survival (time from treatment until disease worsens) compared with single-agent Cabometyx in patients with metastatic soft tissue sarcoma, according to results from a phase 2 trial presented at the 2023 ASCO Annual Meeting.

Opdivo and Yervoy are checkpoint inhibitors that work by blocking the PD-1 and CTLA-4 proteins, respectively, which appear on cancer cells and help them hide from the immune system.

“The combination of (Cabometyx) with PD-1 and CTLA-4 inhibition has been studied in other solid tumors and has been shown to be safe in phase 1 studies,” study author, Dr. Brian Van Tine, a professor of medicine in the division of oncology, section of medical oncology, Washington University School of Medicine, said while presenting the findings.

READ MORE: Adding Cabometyx to Immunotherapy Combination Improves Outcomes for Advanced Kidney Cancer

Sixty-nine patients in the study were randomly assigned to receive the three-drug regime, while 36 patients received Cabometyx alone. Additionally, 19 patients crossed over to the Cabometyx/Opdivo/Yervoy regimen when their disease progressed on single-agent Cabometyx.

To be eligible for the trial, patients needed to have an ECOG score of 0 to 1, have undergone one to two prior lines of therapy and be diagnosed with sarcomas that lack translocations. Median age was 59 (range, 35-77) and 61 (range, 19-77) in the triplet and single-agent arms, respectively. On average, patients had 1.7 (range, 1-4) and 1.5 (range, 1-3) prior therapies, respectively among the two groups.

Regarding tumor subtype, 39 and 19 patients in the triplet and single-agent arms, respectively, had a diagnosis of leiomyosarcoma; two and one patient had dedifferentiated liposarcoma; two and three patients had undifferentiated pleomorphic sarcoma; and 26 and 13 patients had a disease histology classified as “other.”

Study findings showed similar response rates between the two groups: 11% in the immunotherapy-containing arm, which included five partial responses (disease shrunk but did not disappear) and two complete responses (disease completely disappeared); and 6% in the Cabometyx-only arm (two partial responses and no complete responses).

“What becomes interesting is the crossover arm — it's allowed after RECIST (criteria-determined) progression — we added (Yervoy) and (Opdivo) and we had an additional two (partial responses) in (patients with) leiomyosarcoma,” Van Tine explained.

The average progression-free survival for the three-drug group was 5.4 months, compared to 3.8 months in the Cabometyx-only arm, indicating a significant improvement in this endpoint thanks to the addition of the two immunotherapy agents.

Disease control rate for the Cabometyx/Opdivo/Yervoy group was 80%, including 41 patients who had stable disease, and then the five partial and two complete responses. Meanwhile, in the Cabometyx group, the disease control rate was 42% (11 stable disease and two partial responses).

Regarding side effects, the most common moderate to severe side effects that affected 10% or more of patients in the three-drug group included hypothyroidism, diarrhea, mucositis, oral dysesthesia (painful and burning feelings in the mouth), nausea, vomiting, elevated AST and ALT (levels that could indicate liver damage), anorexia, taste changes, headache, itchy skin, macopapular rash and high blood pressure.

For patients who were only given Cabometyx, the most common side effects were diarrhea, oral dysesthesia, fatigue, hand-foot syndrome and hypertension.

“Correlative work is ongoing, and updated response data will be presented soon,” Van Tine concluded.

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