medwireNews: Results from two studies presented at the virtual 2020 ASCO Annual Meeting suggest that the strategy of using single-agent nivolumab followed by response-adaptive or salvage add-on ipilimumab cannot be recommended for patients with advanced renal cell carcinoma (RCC).
Discussant Laurence Albiges (Institut Gustave Roussy, Villejuif, France) put these findings in the context of the recently reported and very similar TITAN RCC study, and noted the “limited activity and lack of complete responses” with nivolumab monotherapy.
She also drew attention to the 8–48% of patients who were unable to receive subsequent ipilimumab due to rapid disease progression in the current studies.
Albiges therefore believes that although treatment optimization is a key goal for the field, “this strategy cannot be yet implemented in routine [care],” but added that it could be perhaps considered for frail patients.
The first study, reported by Rana McKay (University of California San Diego, USA), addressed the questions of optimal duration of nivolumab maintenance therapy in responders and feasibility of a response-adaptive approach to adding ipilimumab in nonresponders.
A total of 83 patients with treatment-naïve or previously treated metastatic RCC were enrolled in the phase 2 OMNIVORE trial and initiated induction treatment with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks. Patients who responded within 6 months stopped treatment whereas those with stable or progressive disease were then offered two doses of add-on ipilimumab 1 mg/kg at 3-week intervals.
The objective response rate (ORR) within 6 months of nivolumab treatment was 14% (all partial responses), with similar rates for treatment-naïve and pretreated participants, at 17% and 12%, respectively.
These 12 responders stopped treatment, with five remaining off nivolumab at 1 year post-discontinuation, although one patient restarted nivolumab after 19 months. Three patients remain off nivolumab with a follow-up of less than 8 months, while four patients restarted nivolumab – two with add-on ipilimumab – within 6 months of discontinuation.
For the 57 nonresponding patients with stable or progressive disease, add-on ipilimumab achieved a partial response in two patients, giving an ORR of 4%. Both had received prior treatment for advanced disease and had progressive disease as the best response to nivolumab induction.
The majority (95%) discontinued treatment over a median of 3.7 months, primarily due to disease progression (65%), with unacceptable toxicity the next most common reason (21%).
McKay therefore concluded: “Currently we cannot recommend a strategy of nivolumab followed by response-based addition of ipilimumab.”
She added that “while a subset of patients treated with nivolumab alone can maintain durable responses off treatment at 1 year, early nivolumab discontinuation in the absence of toxicity cannot currently be recommended.”
Michael Atkins (Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA) presented the phase 2 HCRN GU16-260 trial, which evaluated first-line nivolumab monotherapy in 123 patients with metastatic clear cell RCC, followed by the use of salvage nivolumab plus ipilimumab in nonresponders.
Participants received six doses of nivolumab 240 mg every 2 weeks, followed by four doses at 360 mg every 3 weeks and then at a dose of 480 mg every 4 weeks for up to a total of 96 weeks.
After a median follow-up of 15.9 months, the ORR was 31.7%, with complete responses in 5.7% and partial responses in the remaining 26.0%.
Sixty-five participants had stable or progressive disease at the 48-week mark and were therefore eligible to receive salvage treatment with four doses of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks, followed by maintenance nivolumab for up to 48 weeks.
Of these, 34 went on to receive salvage therapy, which achieved an ORR of 13.3% (all partial responses) among the 30 evaluable patients.
Atkins said that nivolumab monotherapy could be “an alternative frontline approach,” especially for patients who are averse to ipilimumab or VEGFR–tyrosine kinase inhibitors.
He admitted, however, that the nivolumab–ipilimumab combination “is likely preferred over [nivolumab] monotherapy when possible” due to better outcomes than those observed with the single agent and “the limited ability to salvage patients with later use of the combination.”
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This independent news story was supported by an educational grant from Pfizer and Merck KGaA
2020 ASCO Annual Meeting; 29–31 May (Abstract 5005)
2020 ASCO Annual Meeting; 29–31 May (Abstract 5006)