IMmotion151 supports atezolizumab–bevacizumab for untreated metastatic RCC
medwireNews: In patients with previously untreated metastatic renal cell carcinoma (RCC), progression-free survival (PFS) is significantly longer with the combination of atezolizumab and bevacizumab than with sunitinib, phase III study findings indicate.
Following encouraging results in a phase II trial of the combination, which pointed to “a complementary effect,” the IMmotion151 investigators randomly assigned 915 patients to receive first-line atezolizumab 1200 mg plus bevacizumab 15 mg/kg by intravenous infusion every 3 weeks or oral sunitinib 50 mg/day on the standard 4 weeks on, 2 weeks off schedule.
At a median follow-up of 15 months, the co-primary endpoint of investigator-assessed PFS in the programmed cell death ligand 1 (PD-L1)-positive population (≥1% expression in tumor infiltrating immune cells) was significantly improved for the 178 patients given atezolizumab plus bevacizumab compared with the 184 who received sunitinib, at a median of 11.2 versus 7.7 months and a hazard ratio (HR) of 0.74.
The other primary endpoint of overall survival in the intention-to-treat (ITT) population – comprising 454 participants in the combination arm and 461 in the sunitinib arm – was immature at this first interim analysis, presenting author Robert Motzer (Memorial Sloan Kettering Cancer Center, New York, USA) told delegates of the 2018 ASCO Genitourinary Cancers Symposium, held in San Francisco, California, USA.
PFS in the ITT group – a secondary endpoint of the trial – was again longer for the patients who received the combination of the PD-L1 inhibitor and the VEGF blocker versus those given the multikinase inhibitor sunitinib (median 11.2 vs 8.4 months, HR=0.83).
Forty-three percent of patients in the combination group achieved an objective response, the median duration of which was unreached at data cutoff – this compared with a response rate of 35% in the sunitinib arm, lasting a median of 12.9 months.
Motzer commented that the safety profile of the atezolizumab–bevacizumab duo is “one of its strongest attributes,” with adverse events of grade 3 or 4 occurring in 40% of participants, compared with 54% of sunitinib-treated patients, and “a relatively small” number of discontinuations as a result of toxicity, at 12% versus 8%.
He pointed out that proteinuria was the only grade 3 or 4 event that occurred more frequently with the combination than with sunitinib, while a number of toxicities – including diarrhea, hand–foot syndrome, fatigue, and asthenia – were more common with sunitinib.
The incidence of adverse events of special interest, that is, immune-related events, was in general low and few were of grade 3–4, at around 3% for the combination and around 4% for sunitinib alone.
“These study results support the use of atezolizumab plus bevacizumab as a first-line treatment option in metastatic RCC,” the presenter concluded.
Speaking to the press, he emphasized: “For an aggressive cancer like this, where less than 20% of people survive 5 years after diagnosis, we think a 3.5 month longer progression-free survival, given the tolerability for this new combination treatment regimen, is an important development.”
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