Episode 8: Rechallenging with immune checkpoint inhibitors does not benefit mRCC patients after progression

In this episode of WND, Prof Emmanuel Seront from UCL Louvain and Prof Vulsteke from Maria Middelares Gent discuss the CONTACT-03 trial, recently presented at ASCO, which has significant consequences for clinical practice.

In metastatic renal cell cancer (mRCC), immune checkpoint inhibitors (ICI) are SOC in first-line treatment, either in combination with IO-IO or IO-TKI. Following the progression after ICI, treatment options are limited to single agents like the TKI cabozantinib. The CONTACT-03 trial addresses an important question, being the benefit of rechallenging with ICI in combination with TKI post-ICI progression. In this phase 3 trial, patients with mRCC, predominantly clear cell carcinoma cases, were randomized between treatment with cabozantinib alone or combined with atezolizumab.

With over 500 patients enrolled, the trial’s primary endpoints focused on PFS and OS and interestingly, the outcome was negative. This indicates that there is no benefit in terms of PFS or OS from adding an ICI to cabozantinib treatment. Moreover, there was no observed increase in ORR or DOR. Additional analysis did not reveal any subgroup of patients that benefit from the combined treatment either. Importantly, the addition of atezolizumab increased toxicity, leading to treatment discontinuation in the combination arm.

The outcome of this trial is very clear: discontinuation of ICI upon disease progression is advisable. The findings in the CONTACT-03 trial also warrant caution for this approach in other cancers.