September 19, 2017
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Nivolumab plus ipilimumab outperforms sunitinib in certain kidney cancers

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Bernard Escudier

MADRID — The immunotherapy combination of nivolumab plus ipilimumab improved objective response rate and prolonged PFS compared with sunitinib in intermediate- and poor-risk patients with previously untreated advanced or metastatic renal cell carcinoma, according to a phase 3 study presented at the European Society for Medical Oncology Congress.

Perspective from Manuela Schmidinger , MD

“There is an unmet need for additional treatment options in the first-line setting that may provide a meaningful survival benefit including more durable, complete responses for patients with advanced renal cell carcinoma,” Bernard Escudier, MD, former chair of the genitourinary group of the Institut Gustave Roussy in Villejuif, France, said during his presentation. “These results for the combination of nivolumab [Opdivo, Bristol-Myers Squibb] and ipilimumab [Yervoy, Bristol-Myers Squibb] are very encouraging in patients with first-line metastatic renal cell carcinoma who have a very poor prognosis.”

The randomized, open-label CheckMate-214 study compared nivolumab and ipilimumab with sunitinib (Sutent, Pfizer) for the first-line treatment of 1,096 adults with measurable clear-cell metastatic renal cell carcinoma and a Karnofsky performance score of 70 or greater.

Patients in the combination arm (n = 550) received 3 mg/kg nivolumab plus 1 mg/kg ipilimumab every 3 weeks for four doses, followed by 3 mg/kg nivolumab every 2 weeks.

The 546 patients assigned sunitinib received 50 mg once daily for 4 weeks and 2 weeks off in 6-week cycles.

ORR, PFS and OS served as co-primary endpoints. Researchers also evaluated efficacy according to baseline tumor PD-L1 expression.

Minimum follow-up was 17.5 months.

Among intermediate- and poor-risk patients — who comprised 425 patients assigned the combination and 422 assigned sunitinib — ORR was 41.6% for the nivolumab-ipilimumab combination compared with 26.5% for sunitinib (P < .0001). Additionally, 9.4% of patients assigned the combination achieved complete response compared with 1.2% of patients assigned sunitinib.

The median duration of response was not reached (95% CI, 21.82 to not reached) in the combination arm vs. 18.2 months (95% CI, 14.82 to not reached) with sunitinib.

Patients assigned the combination also demonstrated significantly longer median PFS (11.6 months vs. 8.4 months; HR = 0.82; P = .0331).

Notably, greater benefit occurred among intermediate- and poor-risk patients with PD-L1 levels of at least 1% at baseline in terms of ORR (58% vs. 22%) and median PFS (22.8 months vs. 5.9 months; HR = 0.48; 95% CI, 0.28-0.82).

In patients with favorable-risk disease, the combination did not improve ORR (29% vs. 52%; P = .0002) or PFS (15.3 months vs. 25.1 months; HR = 2.17; 95% CI, 1.46-3.22).

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No significant difference occurred between arms for ORR or PFS in the overall composite of patients at any risk.

Researchers noted that PD-L1 expression of at least 1% at baseline was more common in intermediate- and poor-risk patients (combination, 26%; sunitinib, 29%) than among favorable-risk patients (combination, 11%; sunitinib, 12%).

Drug-related adverse events occurred in 93% of patients in the nivolumab-ipilimumab cohort and 97% of patients assigned sunitinib. Fifty-four percent of patients assigned the combination experienced a grade 3 to grade 4 adverse event, and 63% of the sunitinib arm experienced a grade 3 to grade 5 event.

Discontinuation due to toxicity occurred in 22% of patients assigned the combination and 12% assigned sunitinib.

Seven of 159 deaths (1%) in the combination arm were considered drug related, and four of 202 (1%) in the sunitinib arm were considered drug related.

“Patients reported better symptom control with nivolumab and ipilimumab compared with sunitinib,” Escudier said. “These results support the use of nivolumab and ipilimumab as a new first-line standard of care option for intermediate- and poor-risk patients with metastatic renal cell carcinoma.”– by Chuck Gormley

 

Reference:

Escudier B, et al. Abstract LBA5. Presented at: European Society for Medical Oncology Congress; Sept. 8-12, 2017; Madrid.

 

Disclosures: Bristol-Myers Squibb and Ono Pharmaceutical Co. Ltd. funded this study. Escudier reports honoraria from Bristol-Myers Squibb, Bayer, Novartis, Pfizer, Exelixis and Roche. Please see the abstract for a list of all other researchers’ relevant financial disclosures.