Adaptive treatment with nivolumab plus ipilimumab improves outcomes compared with nivolumab alone in patients with intermediate- or poor-risk metastatic renal cell carcinoma (mRCC), according to the final results of the TITAN-RCC trial presented at the European Society for Medical Oncology 2022 congress (ESMO 2022) in Paris, France.

Marc-Oliver Grimm, MD, of Jena University Hospital of Friedrich-Schiller University Jena in Jena, Germany, and colleagues reported findings from 207 patients (median age 65 years) treated with combination therapy after induction therapy between October 2016 and December 2018. After receiving nivolumab induction therapy, patients with early disease progression (week 8) or non-responders at week 16 received 2-4 doses of ipilimumab added to nivolumab. Of the 207 patients, 109 received treatment as first-line therapy and 98 received these treatments as second-line therapy (after tyrosine kinase inhibitor therapy).

The primary study endpoints were objective response rate (ORR) per RECIST criteria in first-line and second-line therapy cohorts. Secondary endpoints included progression-free survival (PFS), overall survival (OS), efficacy of induction, response to boost, and safety.

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At a median follow-up of 27.6 months, the ORR in the first-line group was 36% among recipients of nivolumab with adaptive ipilimumab compared with 28% for those treated with nivolumab alone, a significant difference between the treatment arms. Among patients in the second-line group, the ORR was 32% for patients who received nivolumab with adaptive ipilimumab and 18% for recipients of nivolumab alone.

Median PFS was 6.0 months for the first-line group and 3.7 months for the second-line group. Median OS was 36.1 and 33.7 months, respectively. The investigators observed no new safety signals.

The investigators concluded that TITAN-RCC provides further evidence of improved outcomes associated with the use of nivolumab plus adaptive ipilimumab for mRCC compared with nivolumab alone. Nivolumab plus ipilimumab might be considered as a rescue strategy for patients whose disease progresses after second-line nivolumab, they noted.

The combination of nivolumab plus ipilimumab is a current standard of care for first-line therapy for patients with intermediate- or poor-risk mRCC.

Rana McKay, MD, Associate Professor of Medicine at the University of California, San Diego, and Co-Leader of the Genitourinary Oncology Disease Team at the Moores Cancer Center, La Jolla, California, said this adaptive trial looking at outcomes of therapy escalation with dual checkpoint blockade in patients not demonstrating a response to nivolumab monotherapy is helpful. “The rationale to consider such an approach is to attempt to reduce toxicity and to maximize efficacy by escalating therapy only in those who seem to lack an initial response. As we know, the current frontline strategy is dual therapy for all patients,” Dr McKay said.

This adaptive approach overall showed that the salvage rate and complete response rate are low. “It is critically important to do these studies to understand how we can maximize the efficacy of therapy while also mitigating toxicity,” Dr McKay said.

Pedro C Barata, MD, Associate Professor of Medicine at University Hospitals Seidman Cancer Center in Cleveland, Ohio, agrees, noting that the standard of care in this area is quickly changing and genetic signatures will be playing a bigger role. “There might be some who do fine on monotherapy, but we just don’t know who they are,” Dr Barata said. “We are seeing improved outcomes. Patients are living longer and the quality of life appears to be good. Many are doing better now that we are using combination therapy.”

Disclosures: The study is supported by a grant from Bristol Myers Squibb GmbH & Co. KGaA, Munich, Germany, which also supplied study drugs.


Grimm M, Gonzalez EE, Barthelemy P, et al. Efficacy of a tailored approach with nivolumab and nivolumab/ipilimumab as immunotherapeutic boost in metastatic renal cell carcinoma: Final results of TITAN-RCC. Presented at: ESMO 2022, September 9-13, Paris, France. Abstract 1450MO.