medwireNews: Adjuvant treatment with atezolizumab does not improve the outcomes of individuals with renal cell carcinoma (RCC) at increased risk for recurrence after nephrectomy, indicate phase 3 trial results.
Speaking at the ESMO Congress 2022 in Paris, France, researcher Axel Bex (University College London, UK and The Netherlands Cancer Institute, Amsterdam) noted that the primary endpoint of investigator-assessed disease-free survival (DFS) was comparable between the atezolizumab and placebo groups, as were secondary endpoints such as overall survival (OS).
“These study results do not support adjuvant atezolizumab for treatment of renal cell carcinoma,” write the study authors in a simultaneous publication in The Lancet.
The IMmotion010 trial enrolled 778 patients with RCC with a clear cell or sarcomatoid component who had an intermediate or high risk for recurrence following resection, defined as below:
- T2 and grade 4;
- T3a and grade 3 or 4;
- T3b/T3c or T4 and any grade;
- TxN+ and any grade; or
- M1 no evidence of disease.
At a median follow-up of 44.7 months, investigator-assessed DFS did not differ significantly between participants who were randomly assigned to receive adjuvant atezolizumab 1200 mg every 3 weeks for 16 cycles or 1 year and those given placebo, at 57.2 and 49.5 months, respectively, and a nonsignificant stratified hazard ratio (HR) of 0.93.
The 24-month DFS rates were a comparable 67% in the atezolizumab group and 65% in the placebo group.
The OS analysis was immature at the time of data cutoff, but there was no evidence of a significant reduction in the risk for death with the adjuvant use of atezolizumab relative to placebo; the median OS duration was unreached in both treatment arms and the stratified HR was a nonsignificant 0.97.
Bex presented an exploratory analysis of investigator-assessed DFS by PD-L1 status, which revealed “an interesting signal” hinting at a possible benefit of adjuvant atezolizumab in patients with PD-L1 expression levels of at least 5%, which “warrants further investigation.” In this subgroup, the median OS was unreached with atezolizumab and was 49.5 months with placebo, giving a nonsignificant stratified HR of 0.57 in favor of the immunotherapy.
In conclusion, the presenter highlighted that the IMmotion010 results as well as those of other trials of adjuvant immunotherapy in RCC presented at the conference – such as CheckMate 914 – are contradictory to the findings of the KEYNOTE-564 trial of adjuvant pembrolizumab in the same setting.
Thus, “it is clear that further studies are needed to clarify the role of immunotherapy in the adjuvant setting for RCC,” he commented.
Thomas Powles (Barts Cancer Institute, London, UK), who discussed the presentation, said that although the KEYNOTE-564 study is the outlier, it “is strongly positive” for DFS and the findings are unlikely to be due to chance alone.
He suggested that it’s “plausible that atezolizumab is less active” than pembrolizumab in the adjuvant setting, which might explain the negative results of IMmotion010.
The discussant said that it is important to make patients aware that adjuvant treatment with pembrolizumab “delays progression with a chance of life-changing toxicity” and “may improve OS in the future.” But they should also be told that other immune checkpoint inhibitors “have not been able to replicate the pembrolizumab data creating new uncertainty in renal cancer,” he continued.
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ESMO Congress 2022; Paris, France: 9–13 September
Lancet 2022; doi:10.1016/S0140-6736(22)01658-0