No survival advantage with atezolizumab plus bevacizumab in renal cell carcinoma

January 2022 Cancer trials Nalinee Pathak

In previously untreated metastatic renal cell carcinoma (mRCC) patients, combination immunotherapy (atezolizumab + bevacizumab) did not improve overall survival (OS) as compared to sunitinib monotherapy. The final OS analysis of the IMmotion151 trial was recently published in the journal JAMA Oncology.

An open-label, multicentre, phase III randomised clinical study enrolled 915 patients (73.1% men and 26.9% female) with previously untreated, mRCC. Patients were randomly assigned to receive either atezolizumab (1200 mg, every three weeks, intravenous) + bevacizumab (15 mg/kg, intravenous, every three weeks) (median age: 62 years) or sunitinib (50 mg orally once daily, four weeks on and two weeks off) (median age: 60 years) to assess the efficacy and safety of the treatment combination. The study’s two primary endpoints were progression-free survival (PFS) in PD-L1+ patients and OS in the intention-to-treat (ITT) population. Additionally, the exploratory analysis included OS in PD-L1+, transcriptomic subtypes, and safety.

Main findings

An earlier analysis of PFS after a median follow up of 15 months has reported a prolonged PFS in the atezolizumab-bevacizumab arm versus sunitinib treatment group (15.0 versus 7.7 months, hazard ratio (HR) 0.74; 95% CI: 0.57-0.96; P=0.0217). However, after a median follow-up of 40 months, a similar OS was observed between atezolizumab-bevacizumab and sunitinib groups in the ITT populations (36.1 versus 35.3 months, respectively; HR: 0.91; 95% CI: 0.76-1.08) as well as in patients with PD-L1+ disease (38.7 versus 31.6 months, respectively; HR: 0.85; 95% CI: 0.64-1.13). While there was no overall difference in OS between both treatment arms, different survival outcomes were observed in subset populations. For instance, patients in the angiogenic subset had a shorter OS with atezolizumab-bevacizumab; it was prolonged in the T-effector/proliferative, proliferative, and snoRNA subsets. Adverse events (grade 3 or 4) were observed in the combination arm (46%), with proteinuria being the most common event (8%). Additionally, 28% and 12% of patients discontinued treatment due to adverse events in the combination and sunitinib arm, respectively.

Conclusion

The results of the study report no differences in the survival outcomes with atezolizumab-bevacizumab versus sunitinib in mRCC patients. However, analysing OS in biomarker defined subsets provided a molecular basis of different survival outcomes.

References

Motzer RJ, Powles T, Atkins MB, et al. Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. JAMA Oncol. 2021 Dec 23. Epub ahead of print.

X