Extended duration of anti-PD-1 therapy, using reduced frequency dosing, in patients with advanced melanoma and Merkel cell carcinoma.

Abstract

2588 Background: Optimal duration of treatment (DoT) with immune checkpoint inhibitors (ICI) in patients with metastatic melanoma (Mel) and Merkel cell carcinoma (MCC) is unclear. ICI discontinuation in Mel patients, especially those without CR, may be associated with a higher rate of progression over time, as compared to ICI continuation. Thus, extending DoT could improve outcomes. However, indefinite continuation at standard frequency doses (SFD) is not logistically or financially viable. Based on data from phase I studies suggesting sustained PD-1 receptor occupancy beyond 3 months after a single dose of nivolumab, we employed reduced frequency dosing (RFD) of anti-PD-1 antibodies every 2-3 months, to extend ICI duration beyond 2 years. Methods: This retrospective study analyzes patients in our skin cancer clinic with metastatic Mel and MCC who experienced initial clinical benefit with anti-PD-1 administered at SFD and then transitioned to RFD. We analyzed safety and efficacy endpoints including progression free survival (PFS) and rates of immune-related adverse events (irAE) with RFD. We also compared the pharmaceutical costs and patient-centered costs between 2 years of treatment at SFD versus extended DoT at RFD. Results: From 2014 – 2021, 23 patients with either metastatic Mel (N = 18) or MCC (N = 5) received anti-PD-1 therapy at RFD. Median DoT at SFD in this cohort was 1.1 years (range 0.2 – 2.2) with best objective tumor responses of CR (N =6), PR (N = 11), SD (N = 6). Median DoT at RFD was 1.2 years (range 0.2 – 3.5). The median follow-up for the entire cohort is 3.7 years (range 0.7 – 6.3) after ICI initiation. The 3-year PFS in Mel patients was 100% in those with CR (3/3), 89% with PR (8/9), and 50% with SD (3/6). The 3-year PFS in MCC was 100% in all 5 patients, including patients with CR (3/3) and with PR (2/2). Any-grade irAEs occurred in 43% of patients by 3 years on RFD, and grade 3/4 irAEs presented in 15%. Among the subset of 15 patients with DoT >2 years (median 3.4 yr, range 2.0 – 5.0), total savings amounted to $1.1 million in drugs costs and 384 hours of clinic and travel time despite the increased DoT, as compared to the calculated values for 2-year DoT at SFD. Conclusions: RFD may provide an alternative approach to extending DoT in patients receiving ICI without additional logistical and financial burden, while preserving outcomes. Efficacy and safety data suggest sustained biologic activity of ICI with RFD administration. PK/PD analyses on patient samples are ongoing to further characterize the RFD approach. The RFD approach could be utilized to expand ICI access to communities with limited healthcare resources, thereby impacting cancer outcomes at a global scale.

Real-Life Study of the Benefit of Concomitant Radiotherapy with Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma (cSCC): A Retrospective Cohort Study

“…When cemiplimab was stopped, only one PR patient relapsed at 6 months and one CR patient died during follow-up, whose death was unrelated to the oncological disease. To avoid progression after discontinuation of cemiplimab, we suggest cemiplimab administration spacing in long responder patients, similar to that proposed in melanoma and Merkel's carcinoma [27].…”

A non-inferiority randomized phase III trial of standard immunotherapy by checkpoint inhibitors vs. reduced dose intensity in responding patients with metastatic cancer: the MOIO protocol study

“…For approved immunotherapies, such as PD-1/PD-L1 inhibitors and anti-CTLA-4 agents, treatments are administered until disease progression or unacceptable toxicity, with the exception of metastatic melanoma in complete response for which treatment can be stopped at 6 months. However, the optimal dose, frequency and duration of these therapies are currently unknown and a growing number of studies are reporting maintenance of response despite discontinuation of therapy or extension of IO dose intervals [ 16 , 17 ]. The PRIMS trial, a phase II in metastatic renal cell cancer presented at ESMO meeting 2021, has shown that extending treatment intervals of immunotherapy did not compromise efficacy and reduced toxicity [ 16 ].…”

“…The PRIMS trial, a phase II in metastatic renal cell cancer presented at ESMO meeting 2021, has shown that extending treatment intervals of immunotherapy did not compromise efficacy and reduced toxicity [ 16 ]. A Phase II study in Merckel and metastatic melanoma explored reduced frequency dosing of anti-PD1 with significant efficacy and reduced logistical and financial burden [ 17 ].…”