乌鸦传媒

Nearly one-fifth of patients with intermediate- or poor-risk advanced renal cell carcinoma (RCC) treated with nivolumab (Opdivo) plus ipilimumab (Yervoy) in the CheckMate 214 trial were alive and treatment free beyond 3 years.

Among the phase III trial participants, the treatment-free survival (TFS) rate at 42 months was 18% for those who were randomized to the dual immunotherapy combination versus 5% for those randomized to the prior standard, sunitinib (Sutent), reported Meredith Regan, MD, of Dana-Farber Cancer Institute in Boston, and colleagues.

Mean TFS was 6.9 months for patients treated with nivolumab-ipilimumab versus 3.1 months for those who received sunitinib, "despite longer mean protocol treatment duration, because of delayed time to initiating subsequent therapy for nivolumab plus ipilimumab versus sunitinib," the authors wrote in .

For patients with favorable-risk advanced RCC, the combination therapy led to a mean TFS that was about three times as long compared with sunitinib (11.0 months vs 3.7 months), they noted.

In addition, the 42-month TFS rate among intermediate- or poor-risk patients treated with nivolumab-ipilimumab remained more than twice that compared with sunitinib patients regardless of toxicity:

• TFS without grade ≥3 treatment-related adverse events (TRAEs) was 6.3 vs 2.9 months, respectively
• TFS without grade ≥2 TRAEs was 3.9 vs 1.5 months

"Given the durable response and survival with [immune checkpoint inhibitor] combination relative to VEGF receptor TKI targeted therapy, this integrated analysis of CheckMate 214 demonstrated the value of describing the quality of survival time as a part of comparing their value for both intermediate/poor-risk and favorable- risk populations, and provided additional insight for individual decision-making about initiation of first-line therapy for advanced RCC," Regan and colleagues wrote.

A demonstrated that the 42-month overall survival (OS) probability was 52% in the nivolumab-ipilimumab group versus 39% in the sunitinib group. When looking at favorable-risk patients, 42-month OS probabilities were 70% and 73%, respectively.

Checkmate 214 included 1,096 patients, 550 of whom were randomized to nivolumab-ipilimumab, and 546 to sunitinib. Most patients (77%) had intermediate- or poor-risk disease. Based on the trial results, the combination received FDA approval for intermediate- and poor-risk patients.

The authors pointed out that while OS was similar among favorable-risk patients in the two treatment groups, "the patterns of how patients spent OS were notably different," with 20% of nivolumab-ipilimumab patients and 9% of sunitinib patients being treatment-free at 42 months.

Over this time period, sunitinib patients spent more time on protocol therapy, with approximately two-thirds of that time with grade ≥2 TRAEs. In contrast, the patients in the combination arm spent more time treatment-free and without grade ≥2 TRAEs.

"In this patient subgroup, by definition with minimal symptoms of their cancer, the tradeoffs of time on therapy and adverse events of the therapy as well as their health-related quality of life implications are key features of decision-making when initiating first-line therapy," Regan and team wrote.

"The novel TFS outcome complements OS, progression-free survival, and other outcomes that might impact clinical decision-making with an integrated summary of how OS time is spent," they concluded, suggesting that clinical trials on immune checkpoint inhibitors should assess TFS to determine the quality of survival time.

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