Treatment-free Survival after Immune Checkpoint Inhibitor Therapy versus Targeted Therapy for Advanced Renal Cell Carcinoma: 42-Month Results of the CheckMate 214 Trial

Abstract

Purpose: Patients discontinuing immuno-oncology regimens may experience periods of disease control without need for ongoing anticancer therapy, but toxicity may persist. We describe treatment-free survival (TFS), with and without toxicity. Patients and Methods: Data were analyzed from the randomized phase III CheckMate 214 trial of nivolumab plus ipilimumab (n = 550) versus sunitinib (n = 546) for treatment-naïve, advanced renal cell carcinoma (aRCC). TFS was estimated by the 42-month restricted mean times defined by the area between Kaplan–Meier curves for two time-to-event endpoints defined from randomization: time to protocol therapy cessation and time to subsequent systemic therapy initiation or death. TFS was subdivided as TFS with and without toxicity by counting days with ≥1 grade ≥3 treatment-related adverse event (TRAE). Results: At 42 months since randomization, 52% of nivolumab plus ipilimumab and 39% of sunitinib intermediate/poor-risk patients were alive; 18% and 5% surviving treatment-free, respectively. Among favorable-risk patients, 70% and 73% of nivolumab plus ipilimumab and sunitinib patients were alive; 20% and 9% treatment-free. Over the 42-month period, mean TFS was over twice as long after nivolumab plus ipilimumab than sunitinib for intermediate/poor-risk (6.9 vs. 3.1 months) and three times as long for favorable-risk patients (11.0 vs. 3.7 months). Mean TFS with grade ≥3 TRAEs was a small proportion of time for both treatments (0.6 vs. 0.3 months after nivolumab plus ipilimumab vs. sunitinib for intermediate/poor-risk, and 0.9 vs. 0.3 months for favorable-risk patients). Conclusions: Patients initiating first-line nivolumab plus ipilimumab for aRCC spent more survival time treatment-free without toxicity versus those on sunitinib, regardless of risk group.

Elevated eosinophils as predictor of immune-related adverse events after ipilimumab and nivolumab treatment of advanced and metastatic renal cell carcinoma

“…≧3 tended to be shorter than that of patients who did not experience an irAE of grade ≧3 (0.6 months and 6.1 months, respectively; 33 ). Several studies have shown that the discontinuation of treatment by the onset of irAEs was associated with a poor clinical outcome 34,35 .…”

Evolving landscape of first-line combination therapy in advanced renal cancer: a systematic review

“… 40 Furthermore, treatment-free survival after the dual ICI combination was over twice that of sunitinib for intermediate/poor-risk (6.9 versus 3.1 months) and three times as long for favorable-risk patients (11.0 versus 3.7 months), suggesting that the ICI combination could allow for more treatment breaks. 50 However, acute immune-related AEs were observed that required careful monitoring and carry both the risk of treatment discontinuation and ongoing management for persistent complications. 30 Overall, however, the safety profile of the dual ICI combination was consistent with previous studies in RCC and other tumor types, 51 – 55 with dose delays, rapid diagnostic workups, appropriate timing, and the use of glucocorticoids (28.7% of patients received ⩾40 mg prednisone daily or equivalent) to manage any grade treatment-related select AEs.…”

First-Line Treatments for Metastatic Clear Cell Renal Cell Carcinoma: An Ever-Enlarging Landscape

“…Treatment-free survival intervals are also important; when compared with patients who received sunitinib, patients who received ipilimumab-nivolumab had more breaks off of systemic therapy and more time without side effects. 21 …”