medwireNews: Real-world study data show that a high proportion of patients with metastatic clear cell renal cell carcinoma (ccRCC) gain clinical benefit from treatment with cabozantinib following progression with immune checkpoint inhibitors (ICIs).
Toni Choueiri (Dana-Farber Cancer Institute, Boston Massachusetts, USA) and co-investigators say the findings compare favorably with those of the pivotal METEOR trial, which showed that cabozantinib is effective in the second-line treatment of metastatic ccRCC.
However, only 9% of patients randomly assigned to treatment with cabozantinib in that trial had previous ICI exposure and these drugs are now beginning to play a larger role in earlier lines of therapy, they explain.
Choueiri and team therefore assessed activity of the VEGF receptor inhibitor in 86 patients (median age 63 years) with metastatic ccRCC who had progressed on anti-PD1/PD-L1-based ICIs.
Of these, 64% had previously received an ICI alone or in combination with another ICI, 29% received an ICI in combination with a VEGF inhibitor, and 7% were treated with an ICI plus investigational immunotherapy or targeted therapy agents. The median number of prior lines of therapies was two.
Just over half (52%) of patients initiated cabozantinib at the full dose of 60 mg/day and 44% started at 40 mg/day.
During a median 12 months of follow-up, the objective response rate (ORR) was 36%, all of which were partial responses. A further 43% of patients had stable disease, resulting in a clinical benefit rate of 79%.
The median time to treatment failure was 6.5 months and the median overall survival duration was 13.1 months, with 55% of study participants alive at 12 months.
When the researchers analyzed the data according to prior ICI exposure, they found that the ORR was 42% when cabozantinib was given after ICI monotherapy or combined ICI therapy, and 28% when given after an ICI–VEGF inhibitor combination.
In terms of safety, 45% of patients needed a dose reduction due to a treatment-related adverse event (TRAE). The most common reasons for dose reductions were fatigue (27%), palmar–plantar erythrodysesthesia (16%), and diarrhea (10%).
In addition, 16.3% of patients discontinued treatment because of TRAEs, with fatigue, liver function test abnormalities, diarrhea, and pulmonary toxicity all occurring in two patients each.
Writing in the European Journal of Cancer, Choueiri and co-authors conclude that their findings “suggest that cabozantinib is an effective therapy for the treatment of patients with metastatic ccRCC who had been previously treated by [ICI]-based regimens.”
They add that “[t]he efficacy of cabozantinib appears to be conserved regardless of whether patients had received VEGF [inhibitors], either sequentially or concurrently with [ICIs], and even in patients who had been very heavily pretreated.”
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