medwireNews: Extended follow-up of patients with unresectable locally advanced or metastatic urothelial carcinoma (mUC) in the CheckMate 032 trial shows sustained antitumor activity of nivolumab alone and in combination with ipilimumab.
The “greatest antitumor activity” was seen with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (NIVO1+IPI3), which “not only supports additional study of NIVO1+IPI3 in mUC, but demonstrates the potential benefit of immunotherapy combinations in this disease,” say the researchers.
The multicenter phase I/II study included 274 patients with platinum-treated mUC who received one of three doses and combinations of nivolumab plus ipilimumab until disease progression or unacceptable toxicity.
Padmanee Sharma (The University of Texas MD Anderson Cancer Center, Houston, USA) and colleagues report that after a minimum 7.9 months of follow up, the highest objective response rate (ORR) was observed among the 92 patients who received NIVO1+IP3, at 38.0%.
This compared with an ORR of 26.9% among the 104 patients treated with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (NIVO3+IPI1) who were followed up for a minimum of 38.8 months.
And the lowest ORR was 25.6% among the 78 patients who received nivolumab 3 mg/kg monotherapy every 2 weeks (NIVO3) and were followed-up for a minimum of 37.7 months.
The researchers note that responses were observed irrespective of PD-L1 expression levels in all treatment arms but were higher among patients with expression levels of 1% or greater at baseline.
The median duration of therapy was 3.2, 2.1, and 3.5 months with NIVO1+IPI3, NIVO3+IPI1, and NIVO3, respectively, with corresponding median response durations of 22.9, 22.3, and 30.5 months.
Sharma and team also point out that the “promising efficacy observed with the NIVO1+IPI3 combination” was reflected in longer progression-free and overall survival times, at 4.9 and 15.3 months, respectively, versus 2.6 and 7.4 months with NIVO3+IPI1 and 2.8 and 9.9 months with NIVO3.
There were no unexpected safety signals observed and the rates of grade 3 to 4 treatment-related serious adverse events were 21.7%, 20.2%, and 7.7% with NIVO1+IPI3, NIVO3+IPI1, and NIVO3, respectively. Grade 5 treatment-related pneumonitis was reported in one patient in the NIVO3 arm and one in the NIVO3+IPI1 arm.
Writing in the Journal of Clinical Oncology, Sharma et al say that their findings “in this heavily pretreated population are encouraging as it is known that these patients have limited subsequent treatment options.”
The authors accept that the study is limited by the lack of direct comparison among the treatment arms or with current clinical practice, but “the ongoing phase III CheckMate 901 trial will further evaluate the NIVO1+IPI3 combination versus chemotherapy in patients with previously untreated mUC,” they write.
The team concludes that their findings “provide a strong rationale by which to evaluate NIVO1+IPI3 in the first-line setting for mUC.”
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group
J Clin Oncol 2019; doi:10.1200/JCO.19.00538
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