The CABATEN/GETNE-T1914 study constituted a comprehensive investigation across multiple cohorts to assess the synergistic impact of cabozantinib, a multi-kinase inhibitor, and atezolizumab, a PD-L1 inhibitor. The outcomes yielded results of moderate significance. The scrutiny of signals from novel drugs or their combinations holds paramount importance, particularly in rare cancer types. Lessons drawn from the DUNE trial, encompassing nearly 130 patients with neuroendocrine tumours, underscored the discouraging implications of immunotherapy, rendering it an irrepeatable strategy for a substantial patient cohort.
The CABATEN study was distinctive in its design, featuring six cohorts, albeit criticized for its aggressive approach, each comprising a mere nine patients. Patients not exhibiting an initial response were not transitioned to a secondary treatment stage. This design posed the risk of potentially overlooking patients who might have benefited due to the limited sample size. Conversely, a substantial treatment response would have been conspicuous within this small cohort. Absent such a response, it is prudent to explore alternative combinations rather than focusing on minute subgroups potentially responsive to the treatment.
The combination of cabozantinib and atezolizumab demonstrated efficacy in adrenocortical and anaplastic thyroid cancer groups, with the latter exhibiting prior responses to immunotherapy in earlier studies. Furthermore, the combination of durvalumab and tremelimumab augmented positive responses by 30%.
This prompts the question of whether treatment with a PD-L1 inhibitor in isolation suffices. Insights from this and preceding studies suggest no added benefit from dual immunotherapy. Evaluation of PD-L1 expression will be conducted through CPS and TPS scores. Next-generation sequencing (NGS) testing for mutations, encompassing not only MSI (Microsatellite Instability) due to its rarity, will be conducted to elaborate on our findings.
Presently, the evidence does not substantiate the necessity for a CPS score within the CABATEN study cohorts. The foremost analysis in anaplastic tumours will focus on BRAF mutations. Affirmation of such mutations will prompt the commencement of patients on BRAF inhibitors, either independently or in combination with MEK inhibitors. In cases where BRAF mutations are absent, a regimen comprising a multi-kinase inhibitor and a PD-L1 inhibitor will be initiated. Combination therapy remains the preferred & approach, given the inadequacy of immunotherapy in isolation.
References:
Capdevilla Castillon J. – Cabozantinib plus atezolizumab in advanced and progressive neoplasms of the endocrine system: A multi-cohort basket phase II trial (CABATEN/GETNE-T1914). ESMO2023
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