medwireNews: Maintenance treatment with cabozantinib after platinum-based chemotherapy does not significantly improve the outcomes of unselected patients with metastatic urothelial cancer (mUC) relative to placebo, indicate findings from ATLANTIS.
Presenting the results at the 2022 ASCO Annual Meeting in Chicago, Illinois, USA, Robert Jones (University of Glasgow, UK) noted that patients included in the cabozantinib comparison of the adaptive trial platform were “unsuitable for inclusion in the precision medicine arms” and “negative patient selection for DNA repair deficiency or androgen receptor biomarkers may have biased this interpretation.”
Robert Jones explains why the ATLANTIS trial findings do not support the use of single-agent cabozantinib for the maintenance treatment of metastatic urothelial carcinoma, and what they mean for the role of VEGFR-targeted therapies in this tumor type (3:23).
He also pointed out that the comparison was underpowered due to changes to the protocol as a result of the COVID-19 pandemic and the release of the JAVELIN Bladder 100 data supporting the use of avelumab in the maintenance setting.
Nevertheless, “this study does not support further investigation of cabozantinib alone as a maintenance therapy” in this population, said Jones, adding that “future trials should consider combining novel agents with maintenance immunotherapy.”
The cabozantinib comparison of the double-blind, phase 2 ATLANTIS trial included 61 patients (instead of the planned 140) with stage IV urothelial cancer who derived clinical benefit (response or stable disease) from four to eight cycles of first-line chemotherapy, and did not harbor DNA repair deficiency or androgen receptor biomarkers. Participants were randomly assigned to receive either cabozantinib 40 mg/day or placebo as maintenance therapy.
The primary endpoint of investigator-assessed progression-free survival did not differ significantly between the cabozantinib and placebo groups, at a median of 13.7 and 15.8 weeks, respectively. The hazard ratio for progression or death of 0.89 numerically favored the multikinase inhibitor but did not meet the prespecified criteria for statistical significance.
Overall survival was similarly comparable between cabozantinib- and placebo-treated participants, at a median of 75.5 versus 82.9 weeks.
With regard to the toxicity profile, patients in the cabozantinib group were significantly more likely than those in the placebo group to experience any-grade fatigue (56.7 vs 32.2%), hypertension (43.3 vs 12.9%), diarrhea (40.0 vs 6.5%), anorexia (30.0 vs 9.7%), rash (26.7 vs 3.2%), hypothyroidism (20.0 vs 3.2%), and neutropenia (16.7 vs 3.2%).
But “these are all recognized and manageable toxicities for cabozantinib,” noted Jones.
Forty-three percent of patients receiving cabozantinib required a dose reduction, compared with 10% of those given placebo, but no patient in either group discontinued treatment as a result of toxicity.
Shilpa Gupta (Taussig Cancer Institute, Cleveland, Ohio, USA), who discussed the presentation, agreed that “single-agent cabozantinib does not warrant further study” in this setting.
She believes that the “[b]iomarker analysis from this trial will be crucial to inform patient selection in future anti-angiogenesis therapy trial designs.”
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This independent news story was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany