Nivolumab-mediated adverse events are independent of efficacy in resected advanced melanoma

Medical writer: Dr. Rachel H. Giles

Prof. Mario Mandalà (Papa Giovanni XXIII Cancer Centre Hospital, Bergamo, Italy) provided data from CheckMate 238 plotting treatment-related adverse events (TRAEs) for nivolumab in patients with resected stage IIIB/C or IV melanoma against recurrence-free survival (RFS). His comprehensive analysis demonstrated a safety profile consistent with the other nivolumab studies. The majority of TRAEs with adjuvant NIVO occurred early during treatment, and patients had a reduced frequency of TRAEs after the treatment course. Most TRAEs resolved within 3 months [1].

CheckMate 238 demonstrated that adjuvant treatment with nivolumab significantly improved RFS for patients with stage III/IV melanoma with pathologic involvement of regional lymph nodes >1 mm who have undergone complete resection including total lymphadenectomy, reducing the risk of recurrence or death by 35% compared with ipilimumab (HR, 0.65; 97.56% CI, 0.53-0.80; P <0.001). Besides showing clear benefit under the nivolumab arm, initial results also showed significantly less toxicity, although it was unclear if toxicity related to efficacy. The proportion of patients under nivolumab arms who had to stop therapy from TRAE’s was 8% compared >30% of those who were on the ipilimumab arms.

In the current study, Prof Mandalà and colleagues performed a subgroup analysis of CheckMate 238 patients (N=453) using discrete follow-up intervals and interrogated a putative association of these AEs with efficacy (RFS). The primary endpoint was RFS. Patients were followed for safety for up to 100 days following their last dose; as of the previous 18-month database lock, all patients had been off study drug for > 100 days. Safety data were analysed within the pre-defined time intervals: 0–3 months of treatment, 3–12 months of treatment, and from the last dose to 100+ days after the last dose.

The incidence of the first onset of TRAEs reported in ≥5% of patients was highest in the 0–3 month time frame; the most common TRAEs with nivolumab were fatigue (28% for 0–3 months vs 6% for 3–12 months vs 2% for +100 days post-last dose), pruritus (16% vs 7% vs 1%, respectively), and diarrhoea (15% vs 7% vs 2%, respectively). Most TRAEs with nivolumab resolved within 3 months of occurrence, except for endocrine AEs, which could have required hormone supplementation, and skin AEs (median overall resolution time of 48 and 22 weeks, respectively). The authors concluded that there was no correlation between TRAE’s and RFS.

1. Mandalà M et al. Abstract 9584. ASCO 2019, 31 May-4 June, Chicago, USA.

Posted on 15 July 201925 March 2021