Immunotherapy with nivolumab and pembrolizumab in unresectable or metastatic advanced melanoma: real-life observational study of drug use.

Abstract

In Italy, the monoclonal antibodies nivolumab and pembrolizumab are subjected to the AIFA monitoring registries for the indication "advanced melanoma (unresectable or metastatic) in adults". These two drugs have the same eligibility criteria, and they are indicated until failure due to progression or toxicity; both of these drugs have also undergone dosage changes from pro/kg to flat dose. In this observational study, also based on clinical eligibility parameters, we wanted to investigate the rwTTD, definitive and temporary suspensions, as well as dose modifications. We enrolled patients who started a treatment with nivolumab or pembrolizumab and were admitted to the Regina Elena National Cancer Institute in the period between 01/01/2016 and 31/12/2018. Treatments were followed up to 31/01/2021. Data were collected from the AIFA monitoring registries and from local therapy monitoring databases. We used the Kaplan-Meier method to estimate rwTTD, and the differences between sample subgroups were evaluated using the Log-Rank Test. In the 123 patients enrolled, the rwTTD was 11.67 months (IC 95%: 7,93-17,27). On average, about one out of five patients stopped the therapy before 2 months. The treatments suspended for at least 45 consecutive days and then resumed were 49 (47.6%) with rwTTD= 26.4 months (95% CI 17.3-43.6), significantly higher (p=0.008) compared to treatments suspended for less than or equal to 45 days (rwTTD= 8.4 months (95% CI 4.3-17.1). Dosage changes of nivolumab from pro/kg to flat dose ended in percentage ranging from -23.8% to +56.9%, mean +7.2%. In the case of pembrolizumab, the transition to the flat dose led to variations between +22% and +81.8%, average +39.9%. Patients who temporarily stopped the treatment had a median rwTTD that is three times higher than patients who stopped permanently and had at least 45 days of therapy. Other studies suggest that patients who had immunological response and side effects, then had better PFS and OS than those without side effects. It is confirmed that it is therefore important to manage toxicities and then resume treatment, whenever possible. In patients who switched to a flat dose, there was an evident increase in the dose administered, especially for pembrolizumab.