Nivolumab/ipilimumab bests sunitinib monotherapy

Treatment-naïve patients with advanced renal cell carcinoma (RCC) treated with the immune checkpoint inhibitor combination of nivolumab plus ipilimumab experienced a longer treatment-free survival (TFS) interval than patients who received targeted therapy with sunitinb, regardless of their prognostic risk, the phase III, CheckMate-214 study found.

Over a follow-up interval of 42 months, mean TFS was 6.9 months for the combination arm compared with 3.1 months (95% CI, 2.5-5.0 months) for sunitinib among patients with intermediate/poor risk renal cancer, Meredith Regan, ScD, Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues reported in Clinical Cancer Research.

Among the smaller subgroup of patients with favorable risk disease, the mean TFS interval was 3 times as long at 11 months for those who received dual ICI blockade compared with 3.7 months (difference 7.3 months (95% CI, 4.6-10 months) for those who received targeted therapy, investigators added.

However, as the authors emphasized, there was a difference in how this time was spent between the two groups: at 42 months, 20% of patients treated with the combination therapy were treatment-free compared with only 9% of patients in the sunitinib monotherapy arm.

Patients with favorable risk disease in the sunitinib group also spent more time on treatment and experienced moderate treatment-related adverse events (TRAEs) for longer than those who received nivolumab plus ipilimumab.

“We knew from the previous CheckMate-214 analysis that nivolumab plus ipilimumab improved survival compared with sunitinb; now, we are able to compare the way patients spent that overall survival time on these 2 different treatment approaches,” Regan said in a statement.

“As we continue to develop new treatments, we have an opportunity to think about new methods to better balance the efficacy and toxicity to patients,” she added.

A total of 1,096 patients were randomized to either nivolumab at a dose of 3 mg/kg of body weight plus ipilimumab at a dose of 1 mg/kg of body weight, given intravenously every three weeks, for four doses, followed by nivolumab at the same dose every two weeks.

Alternatively, they were assigned to oral sunitinib at a dose of 50 mg once a day for four weeks of each six-week cycle.

Most patients in the study had intermediate/poor risk disease, the authors noted.

“TFS and time on protocol therapy were further partitioned into survival states with and without toxicity,” investigators explained. For their analysis, they used two definitions of TRAEs: grade ≥2 and grade ≥3.

At follow-up 42 months after randomization, 52% of patients in the checkpoint inhibitor combination arm were still alive compared with 39% of those who received sunitinib and 31% of the combination group were free of subsequent therapy compared with only 9% of those treated with sunitinib, the authors observed.

“The probabilities of being treatment-free at 42 months were 18% and 4.9%, respectively,” they added.

The mean TFS interval spent without toxicity was also more than twice as long with nivolumab plus ipilimumab than it was with sunitinib, however TRAEs was defined:

  • TFS without grade ≥3 TRAEs: difference 3.4 months (95% CI, 2.2-4.6 months)
  • TFS without grade ≥2 TRAEs: difference 2.4 months (95% CI, 1.4-3.4 months).

Notably, however, the mean TFS interval that patients spent in grade ≥3 TRAEs was less than one month for both treatment groups.

Some 249 patients out of the entire cohort had favorable disease risk, among whom 70.1% of the ICI combination arm versus 73% of those treated with targeted therapy were alive at follow-up, with roughly equal numbers at 29% and 24%, respectively, being free of subsequent treatment.

That said, 42 months after randomization, more combination therapy patients were treatment-free (19.8%) versus those in the sunitinib arm (8.8%).

Interestingly, the mean TFS with grade ≥2 TRAEs was longer at 4.1 months with nivolumab plus ipilimumab compared with 1.4 months with sunitinib, but the mean TFS without toxicity was still three times longer at 6.9 months compared with 2.3 months for the two arms, respectively, (difference: 4.6 months [95% CI, 2.2-7.0 months]), they added.

The mean TFS spent in grade ≥3 TRAEs was also longer for the ICI combination arm at 0.9 months versus 0.3 months for sunitinib patients.

For patients with favorable-risk disease, patients treated with the nivolumab/ipilimumab combination spent an average of 5.2 months with grade ≥2 TRAEs and on average 8.8 months without grade ≥2 TRAEs.

This compared with a mean of 13.7 months that sunitinib patients spent in grade ≥2 TRAEs and a mean of 6.5 months without grade ≥2 TRAEs, researchers noted.

“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,” Regan and colleagues observed.

“This approach can aid decision-making prior to any knowledge about an individual patient’s tolerance and tumor responsiveness to therapy,” investigators suggested, adding, too, that “the tradeoffs of time on therapy and AEs of the therapy as well as their HRQoL (health-related quality-of-life) implications are key features of decision-making when initiating first-line therapy.”

Limitations of the study include the fact that the TFS analysis was done retrospectively, so results need to be interpreted in the context of the existing protocol.

  1. The first-line immune checkpoint inhibitor combination of nivolumab plus ipilimumab prolonged treatment-free survival compared with targeted monotherapy with sunitinib in advanced renal cell cancer patients.

  2. The time spent without toxicity during the treatment-free interval was also more than double with dual ICI therapy compared with sunitinib.

Pam Harrison, Contributing Writer, BreakingMED™

The study was funded by Bristol Myers Squibb (BMS), the Ono Pharmaceutical Company and the National Cancer Institute.

Regan reported having received research grants from Novartis, Pfizer, Ipsen TerSera, Merck, Ferring, Pierre Fabre, Roche, AstraZeneca, Bayer and consulting fees from Ipsen/Debiopharm, BMS and Tolmar Pharmaceuticals.

Cat ID: 935

Topic ID: 78,935,730,935,127,192,925