Checkpoint inhibitor rechallenge fails to improve outcomes in metastatic kidney cancer
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Key takeaways:
- Patients treated with atezolizumab plus cabozantinib had 1-year PFS of 44% compared with 48% cabozantinib alone.
- Investigators noted increased toxicity with the combination therapy.
CHICAGO — The addition of atezolizumab to cabozantinib failed to improve clinical outcomes for patients with metastatic renal cell carcinoma who experienced progression on or after immune checkpoint inhibitor therapy, study results showed.
Subgroup analysis of the randomized phase 3 CONTACT-03 trial, presented at ASCO Annual Meeting, did not identify any subset of patients who may benefit from the combination, according to researchers.
“We are noticing, in practice, some practitioners rechallenging with an immune checkpoint inhibitor after prior progression on immune checkpoint inhibitors,” Toni K. Choueiri, MD, director of Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, told Healio. “So, when we looked at the data not just in renal cell cancer but others, as well, there weren’t many phase 3 trials ... and yet we found no benefit (in this study) ... not in PFS, not in OS and not in response rate; instead we found a bit of increased toxicity.”
Background and methodology
Patients with advanced kidney cancer typically receive immune checkpoint inhibitors as first-line treatment. Prospective evidence supports the use of VEGF tyrosine kinase inhibitors, such as cabozantinib (Cabometyx, Exelixis) for patients with metastatic disease who previously received checkpoint inhibitor-based regimens.
Choueiri and colleagues conducted CONTACT-03 to assess the effects of cabozantinib with or without the anti-PD-L1 antibody atezolizumab (Tecentriq, Genentech) in the second-line setting after immune checkpoint inhibitor therapy.
The study included 522 patients with advanced/metastatic clear cell or nonclear cell renal cell carcinoma with or without a sarcomatoid component and radiographic progression on or after prior immune checkpoint inhibitor treatment.
Patients in the combination group (n = 263; median age, 62 years; 77.6% men) received 1,200 mg atezolizumab IV every 3 weeks along with 60 mg cabozantinib daily, whereas patients in the control group (n = 259; median age, 63 years; 76.1% men) received 60 mg cabozantinib daily.
Centrally reviewed PFS and OS served as primary endpoints, with investigator-assessed PFS, objective response rate, duration of response and safety as secondary endpoints.
Results
Centrally reviewed median PFS did not differ significantly between patients in the combination group (10.6 months; 95% CI, 9.8-12.3) and the control group (10.8 months; 95% CI, 10-12.5), with an HR of 1.03 (95% CI, 0.83-1.28).
Researchers reported 12-month PFS rates of 44% (95% CI, 38-50) with the combination and 48% (95% CI, 42-54) in the control group.
An interim analysis of OS showed a 12-month OS rate of 79% (95% CI, 73-84) among patients treated with the combination and 76% (95% CI, 71-81) among patients treated with cabozantinib alone (stratified HR = 0.94; 95% CI, 0.7-1.27).
A higher proportion of patients in the combination group experienced grade 3/grade 4 treatment-related adverse events (55.3% vs. 47.3%), death due to treatment-related adverse events (1.1% vs. 0%) and serious treatment-related adverse events (24% vs. 11.7%).
The CONTACT-03 trial was the first randomized, phase 3 trial to examine the safety and efficacy of rechallenge with a PD-L1 inhibitor following progression on or after prior PD-L1/PD-1 therapy, according to Choueiri.
“We tried to look at whether any specific subgroups could experience any benefit, but all the hazard ratios were close to 1, so I think the practice of rechallenging with an immune checkpoint inhibitor, specifically atezolizumab and a PD-(L)1 inhibitor, should be examined in depth,” Choueiri told Healio.
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Choueiri TK, et al. Abstract LBA4500. Presented at: ASCO Annual Meeting 2023; June 2-6, 2023: Chicago.
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