Nivolumab in non-small cell lung cancer: is there an upper age limit?

Abstract

Introduction: Recent scientific evidence has led to extensive use of immunotherapy in the treatment of non-small cell lung cancer (NSCLC) patients (pts) pretreated with platinum-based chemotherapy regimens. The checkpoint inhibitor Nivolumab (Opdivo® BMS ™) has shown superior efficacy to standard 2nd-line chemotherapy with greater tolerability, which results in improved quality of life. Aging involves physiologic changes and immunosenescence, aging-related loss of immune function, may have a negative impact on clinical benefit and effectiveness of immunotherapy. The objective of our study was to evaluate disease treatment response, to estimate the incidence and diversity of immune-related adverse events (IrAEs) in pts receiving Nivolumab and to check the relationship with age-associated immune dysregulation. Material and methods: From May 2015 to April 2017, 92 NSCLC pts were treated with nivolumab as a single agent, after disease progression to one or more chemotherapy lines, at a dose of 3 mg/kg every two weeks. Clinical examination and evaluation of adverse reactions were performed every 2 weeks. CT scans was performed every 8-12 weeks to assess tumor treatment response. The study population was divided into two different age groups, under 70 years and over 70 years older. Two aspects of adverse event patterns were measured: incidence rate and different types of adverse events in each of the pts age groups. Results: Of 92 pts 41 were age <70 yrs (45%) and 51 were >70 yrs (55%). ORR in pts group <70 yrs was 43% (PR 23%, SD 20%), similar to that found in older pts group (PR 14%, SD 29%). The incidence of IrAEs was 36% in the first group, 32% in the second group. Most common irAEs among pts >70 were endocrinopathies (11%), colitis (7%) and rash (7%). Some adverse events, such as endocrinopathies and fatigue, appeared most frequently in the pts group <70 yrs (16% and 10% respectively). Conclusions: Immunotherapy represent a valid therapeutic option for NSCLC patients but currently there is little known about the safety of nivolumab in elderly patients that may still respond appropriately to checkpoint inhibitors. The obtained data suggest that nivolumab is well tolerated and there is no significant differences between the two age-groups in terms of efficacy and tolerability. The inclusion of greater number of elderly patients in registration clinical trials will provide helpful informations to clinicians on the safety of immunotherapy in patients aged 70 yrs and older.