KEY TAKEAWAYS
- MAIN-CAV is a phase III trial aimed to evaluate the OS in patients with mUC who receive a combination of Av and CABO compared to Av alone.
- A total of 654 adult patients will be enrolled within 3-10 weeks after their last dose of chemotherapy.
- Eligible patients must have an ECOG PS of 0-1, not have received prior immunotherapy, not have metastases in the central nervous system, and have undergone major surgery in the past four weeks.
- Researchers determined whether adding cabozantinib to avelumab treatment in patients with mUC can lead to better clinical outcomes than avelumab alone.
The current recommended standard of care for patients with metastatic urothelial carcinoma (mUC) who do not experience progression after initial platinum-based chemotherapy is the administration of first-line platinum-based chemotherapy followed by maintenance avelumab (Av).
CABO is an oral inhibitor of receptors in the MET, VEGFR, and TAM families involved in tumor growth, angiogenesis, and immune cell control. When used with PD-1/PD-1L1 inhibitors, it is effective in treating UC. The mix of CABO and Av will work well in patients with mUC, be safe, and improve the benefits of Av maintenance in mUC.
MAIN-CAV is a phase III randomized, multicenter, international study for patients with locally advanced/mUC (including N3-only disease) who did not get worse after 4–6 cycles of any platinum-based chemotherapy (gem-cis, gem-carbo, MVAC, or ddMVAC). Within 3–10 weeks after their last dose of chemotherapy, 654 adult patients were given either Av 800 mg IV every 2 weeks or a mixture of Av and CABO 40 mg orally every day for up to 2 years.
Patients were put into different groups based on how well they respond to 1L treatment (complete response, partial response, or stable disease) and whether or not they had metastases in their organs.
The main goal was overall survival (OS). Based on the assumptions of a one-sided alpha of 0.025, a power of 80%, a median OS of 21 months on the Av arm, and a hazard ratio (HR) of 0.75, a median OS of 28 months was predicted for the CABO-Av combination arm. Key secondary goals included progression-free survival, safety, tolerability, and activity of CABO-Av compared to Av alone based on RECIST 1.1 and iRECIST criteria and PD-L1 status of patients’ tumors. EQ-5D-5L, PROMIS-Fatigue 4a, EORTC QLQ-C30, and EORTC QLQ-BLM30 was used to compare the quality of life (QOL) between people taking CABO-avelumab and those taking avelumab alone. Researchers used baseline archive tissues, baseline and serial blood, ctDNA, stool, and urine to look for biomarkers of response and resistance to Av.
Imaging studies examined the relationship between known and new radio mic signatures and OS, adverse events, and quality of life (QOL). To predict outcomes, both radiologic and biological traits were used.
Source: https://meetings.asco.org/abstracts-presentations/225900
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT05092958
Shilpa Gupta, Karla V. Ballman, Matt D. Galsky, Michael J. Morris, Srikala S. Sridhar, Ronald C. Chen, Timothy An-thy Chan, Yujia Wen, Petros Grivas, Alan Tan, Shiva Baghaie, Jonathan E. Rosenberg/MAIN-CAV: Phase III randomized trial of maintenance cabozantinib and avelumab versus avelumab after first-line platinum-based chemotherapy in patients (pts) with metastatic urothelial cancer (mUC; Alliance A032001)./J Clin Oncol 41, 2023 (suppl 16; abstr TPS4609) DOI 10.1200/JCO.2023.41.16_suppl.TPS4609
