TITAN-RCC showcases tailored immunotherapy approach
medwireNews: Results from the TITAN-RCC trial add support for the use of ipilimumab alongside nivolumab in patients with intermediate- or high-risk advanced renal cell carcinoma (RCC), showing that a personalized strategy is feasible for nonresponders.
The phase II study results were presented at the ESMO Congress 2019 in Barcelona, Spain, by Marc-Oliver Grimm, from Universitätsklinikum Jena in Germany, who said that “TITAN-RCC is the first study to assess the impact of a tailored approach using an immunotherapeutic boost to nivolumab monotherapy.”
He explained that nivolumab monotherapy given after one or more lines of anti-angiogenic therapy achieved an overall response rate (ORR) of 25%, rising to 42% when combined with ipilimumab as a first-line regimen in this population.
Acknowledging that nivolumab–ipilimumab is associated with a higher rate of grade 3–4 treatment-related adverse events (TRAEs) than nivolumab alone, however, the TITAN-RCC team assessed whether ipilimumab can be directed toward patients who do not respond to initial PD-L1 inhibitor monotherapy.
In all, 207 patients with one or no prior lines of tyrosine kinase inhibitor therapy were recruited to the study and given an 8-week induction course of nivolumab 240 mg every 2 weeks. Patients with a complete or partial response to treatment by week 16 were assigned to continue nivolumab and undergo assessment every 6–12 weeks, while patients who experienced early progressive disease at week 8, or stable or progressive disease by week 16, were assigned to receive two nivolumab 3 mg/kg and ipilimumab 1 mg/kg boosts given at a 3-week interval before reassessment.
Responding patients continued to nivolumab maintenance while those with stable or progressive disease received a further two boost doses of nivolumab–ipilimumab, with the final option of continuing nivolumab for responders.
After a median 36.2 weeks of follow-up, the researchers note that 64.3% of the patients received at least one boost cycle of ipilimumab therapy, including 20.4% of the 108 first-line patients and 26.3% of the 99 second-line patients by the end of nivolumab induction.
The primary endpoint of overall response rate (ORR) among the first-line treatment participants was 28.7% for those given nivolumab alone and 37.0% for those who received an ipilimumab boost, with corresponding rates for the second-line treatment patients of 18.2% and 28.3%.
Ipilimumab boost achieved an improvement in the best response for 29.8% of the 47 first-line patients, including a partial response by 12.8%, and 38.6% of the 57 second-line line patients, including a complete or partial response in 10.5%.
Of note, 47.9% of patients receiving first- or second-line treatment who received an ipilimumab boost after progressive disease continued to progress compared with just 5.4% of those who received a boost for stable disease, the presenter highlighted.
Median progression-free survival (PFS) was 5.54 and 3.67 months for the full first-line and second-line patient groups, respectively, versus rates of not reached and 16.6 months for the patients who responded to nivolumab alone, respectively.
Median overall survival was not reached for the first-line and 20.2 months for the second-line patient groups.
Marc-Oliver Grimm said “no new safety signals were identified” with any-grade events affecting 81.6% patients, most commonly skin, gastrointestinal, and fatigue. Grade 3–4 adverse events were reported for 30.4% of patients, most frequently lipase elevation (5.8%) and diarrhea (4.8%).
“TITAN-RCC provides further evidence to the added value of ipilimumab in combination with nivolumab in advanced RCC”, he concluded.
“Further follow-up is ongoing to characterize duration and depth of response, and may support this innovative treatment strategy based on individual response.”
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This independent news article was supported by an educational grant from Pfizer and Merck KGaA