CONTACT-03: Primary PFS Analysis of Atezolizumab Plus Cabozantinib After Progression in mRCC

Updated progression-free survival (PFS) data for the first phase 3, randomized trial to test the benefit of immune checkpoint inhibitor (ICI) rechallenge by direct addition to a control arm in metastatic renal cell carcinoma (mRCC) was presented as a late-breaking abstract at the American Society of Clinical Oncology 2023 Annual Meeting.

ICI-based regimens are considered standard of care for first-line treatment of mRCC. Treatment options after disease progression during or after ICI therapy include single-agent tyrosine kinase inhibitors, including cabozantinib.

CONTACT-03 was designed to evaluate atezolizumab in combination with cabozantinib versus cabozantinib alone for patients with mRCC who progressed during or after ICI treatment. The study enrolled 522 patients with histologically confirmed, inoperable, locally advanced or metastatic clear cell or non-clear cell RCC, regardless of PD-L1 status, who progressed on or after ICI treatment. Patients received either atezolizumab plus cabozantinib (n=263) or cabozantinib alone (n=259). Stratification factors were International mRCC Database Consortium risk factors (0 vs 1-2 vs ≥3); most recent line of prior ICI therapy (adjuvant vs first-line vs second-line); and histology (dominant clear cell without sarcomatoid vs dominant non-clear cell [papillary or unclassified] without sarcomatoid vs clear cell or non-clear cell with any sarcomatoid component).

The primary end points were centrally reviewed Response Evaluation Criteria in Solid Tumours v1.1 PFS and overall survival (OS), and secondary end points included investigator-assessed PFS and safety.

Researchers noted that of the patients in the experimental and control arms, 55% and 51%, respectively, had most recent ICI therapy in the first-line and 10% and 11%, respectively, had sarcomatoid RCC.

After a median follow-up of 15.2 months, no PFS or OS benefit was observed in patients receiving atezolizumab plus cabozantinib.

All-cause grade 3/4 adverse events (AEs) occurred in 68% and 62% of safety-evaluable patients receiving atezolizumab plus cabozantinib versus cabozantinib alone, respectively, and all-cause grade 5 AEs occurred in 6% and 4%, respectively. AEs led to treatment withdrawal in 16% of patients in the experimental arm.

In their concluding remarks, authors commented that “the addition of atezolizumab to cabozantinib did not improve clinical outcomes and led to increased toxicity in patients with RCC who progressed on or after prior ICI treatment,” adding that the results “prompt caution with this approach in other cancers.”