Early nivolumab responders sustained years-long treatment-free survival after treatment discontinuation.
Extended follow-up from the phase 2 response-adaptive OMNIVORE trial (NCT03203473) showed that 50% of patients with advanced renal cell carcinoma (RCC) who achieved an early objective response to nivolumab (Opdivo) monotherapy remained off treatment at 1 year following discontinuation, with 5 of these patients maintaining responses beyond 43 months off therapy, according to findings published in the Journal for ImmunoTherapy of Cancer.¹
With a median follow-up among living patients of 59.4 months in the observation arm (Arm A) and 31.4 months in the salvage ipilimumab (Yervoy) arm (Arm B), the 3-year overall survival (OS) rate from nivolumab initiation was 64% (95% CI, 51%-74%) across the full cohort (n = 83), 83% (95% CI, 48%-96%) in Arm A, and 63% (95% CI, 47%-76%) in Arm B. All 6 of the 12 Arm A patients who remained treatment-free at 1 year were alive at last follow-up, with OS ranging from 48.8 to 85.4 months from nivolumab initiation.
OMNIVORE was a multicenter, phase 2 response-adaptive trial in which all patients with histologically confirmed advanced RCC received induction nivolumab monotherapy, with treatment allocation determined by radiographic response per RECIST 1.1 criteria within the first 6 months of therapy.1,2
Patients achieving a confirmed complete response (CR) or partial response (PR) discontinued nivolumab and entered active observation (Arm A), with reinitiation of nivolumab—and addition of ipilimumab if progression persisted—upon disease progression; patients with stable or progressive disease received 2 doses of ipilimumab added to ongoing nivolumab (Arm B).
Of 83 patients who initiated treatment across 10 US centers, 12 (14%) were allocated to Arm A and 57 (69%) to Arm B, with 14 patients (17%) not undergoing arm allocation because of progressive disease or toxicity.¹ Compared with Arm B, Arm A patients were more frequently treatment-naive (58% vs 44%) and had a higher rate of prior nephrectomy (100% vs 89%).
Among the 12 Arm A patients, 6 (50%; 90% CI, 25%-75%) remained off nivolumab at 1 year following discontinuation, and 5 of these maintained responses beyond 43 months off therapy (range, 43.8-58.2 months), with all remaining alive at last follow-up. One patient reinitiated nivolumab while still in partial response and subsequently achieved a CR, remaining on treatment at 83.2 months from nivolumab initiation.
Among the 6 Arm A patients who experienced progression or reinitiated nivolumab within 1 year, 3 subsequently received nivolumab plus ipilimumab with limited benefit and no responses. At data cutoff, 3 Arm A patients had died and 9 remained alive.¹ In Arm B, all 57 patients discontinued treatment, with a median treatment duration of 3.7 months (range, 1-24.8) and a median progression-free survival from nivolumab plus ipilimumab initiation of 4.6 months (95% CI, 2.7-6.5); 21 deaths were observed in this arm.
Investigators noted that the small number of patients allocated to Arm A precludes definitive conclusions about the durability of response following nivolumab discontinuation, and the lack of a randomized comparator arm limits the ability to attribute outcomes directly to the discontinuation strategy itself. The authors also noted that the treatment landscape for advanced RCC has evolved substantially since OMNIVORE was designed, with multiple immunotherapy-based combinations now established as frontline standards of care.
The authors concluded that a meaningful subset of patients achieving an early objective response to nivolumab monotherapy can sustain prolonged treatment-free survival after a short course of treatment, while salvage ipilimumab in non-responders continues to show limited benefit, reinforcing that upfront concurrent dual checkpoint blockade remains the preferred approach; they called for prospective biomarker-driven studies to identify which patients can safely discontinue treatment.
