Nivolumab ipilimumab combo does not improve DFS for RCC after nephrectomy

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Published: 11 Sep 2022
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Dr Robert Motzer - Memorial Sloan Kettering Cancer Center, New York, USA

Dr Robert Motzer speaks to ecancer about his study of the results from the randomised, phase 3 CheckMate 914 trial. The study explores adjuvant nivolumab plus ipilimumab (NIVO+IPI) vs placebo (PBO) for localised renal cell carcinoma (RCC) at high risk of relapse after nephrectomy.

The CheckMate 914 key inclusion criteria was radical or partial nephrectomy with negative surgical margins > 4 and ≤ 12 weeks before randomisation.

The primary endpoint was disease-free survival (DFS) per blinded independent central review whilst secondary endpoints include overall survival and safety.

The results demonstrated that pts with localised RCC at high risk of relapse after nephrectomy did not meet the primary endpoint of DFS.

Safety of NIVO+IPI was consistent with its known profile in advanced RCC, although the rate of discontinuation due to treatment-related AEs was higher with adjuvant NIVO+IPI vs PBO in this trial.

This was a randomised phase III double-blind trial in which patients that had had a kidney tumour
removed surgically, there was no evidence of metastasis but they were at risk for developing
metastasis or recurrence over the years, were entered on the trial and randomised to a combination
immunotherapy with nivolumab plus ipilimumab versus placebo. The treatment duration was intended
to be six months, a brief course of this combination immunotherapy. The primary endpoint was
disease free survival or essentially recurrence of either metastasis or development of a new tumour
on the other kidney.

Unfortunately the study did not reach its primary endpoint, it did not show a benefit for a short course
of this intense ipilimumab nivolumab combination therapy in delaying or preventing relapse for these
patients.

The field with adjuvant immunotherapy for kidney cancer is evolving. There have been five large
phase III trials that have been developed and run and at this point four of these have read out. One is
really a different study that looked at neoadjuvant but the other three looked at adjuvant therapy with
different drugs, different duration and intensity. So one of those trials with a year of pembrolizumab
did show a benefit in prolonging disease free survival but this trial with combination immunotherapy
with ipilimumab nivolumab six months did not. The third trial which was presented yesterday with
atezolizumab, which is a different kind of immunotherapy, a PD-L1 inhibitor also did not show a
benefit. So it’s early in the field, we’re learning in terms of what are the best drugs to use, what are the
best durations of therapy and the patient population to help move the field forward and really develop
effective adjuvant therapy for our patients.

There was a trend for patients that had very high risk tumours – T4 and N positive – or patients that
had very large kidney tumours that were high grade. There was a trend towards improvement with
ipilimumab nivolumab but certainly those were small subsets. The main population of the trial, which
were the T3 tumours, did not benefit.