Clinical outcomes with early-elective discontinuation of PD-1 inhibitors (PDi) at one year in patients (pts) with metastatic melanoma (MM).

Abstract

10048 Background: Randomized trials of PDi in MM permitted treatment for 2 years (pembrolizumab) or more (nivolumab). However, the optimal treatment duration is unknown, and shorter courses may be effective. We reviewed clinical outcomes of pts who electively discontinued PDi at 1 year at our institution. Methods: We performed a real-world, observational cohort study of pts with MM treated with single-agent PDi from 1/1/2015 to 12/31/2018 at Huntsman Cancer Institute. This was a continuous series of pts who made the joint decision with their provider to electively discontinue PDi at 1 year ( > 6 mos and < 18 mos) in the setting of ongoing treatment response or disease stability. Exclusion criteria: PDi with other systemic therapy, discontinuation due to disease progression or immune-related adverse event, and PDi in neoadjuvant, adjuvant, or clinical trial settings. Local therapies, as in real-world, were allowed. Best objective response (BOR) per RECIST 1.1 at PDi discontinuation, progression-free survival (PFS) and retreatment characteristics were analyzed. Results: Of 485 pts who received PDi, 52 met inclusion criteria. Median age was 60.5 years and 26.9% were female. Median duration of PDi from first to last dose was 11.1 mos (95% CI 10.5 - 11.4). BOR was complete response in 13 (25%), partial response in 28 (53.8%), and stable disease in 11 (21.2%) pts. After median follow-up of 20.5 mos (range 3 - 49.2) from treatment discontinuation, 39 (75%) pts remained without disease progression (median PFS not reached). Only 13 (25%) pts progressed. Median time to progression after treatment discontinuation was 3.9 mos (range 0.7-30.9). Of the 13 pts, 7 immediately underwent successful localized treatment to the solitary site of progression (3 SRS/SBRT, 4 resection; followed by PDi in 2), 5 were retreated with PDi and 1 received BRAF/MEK followed by PDi. Retreatment with PDi controlled disease in all 5 pts. All pts except 1 were alive at data cut-off. Conclusions: In the largest continuous series of pts with MM who electively discontinued PDi after 1 year of treatment, the majority remained without progression on follow-up. Risk of disease progression even in pts with residual disease on imaging was low, and retreatment was effective. Strengths of our study include real-world cohort and treatment pattern analysis. Limitations include single-institution, retrospective design. After prospective validation, elective PDi discontinuation at 1 year may reduce financial and PDi-related toxicity without sacrificing outcomes.

PET/CT scan and biopsy-driven approach for safe anti-PD-1 therapy discontinuation in patients with advanced melanoma

“…Several retrospective studies of patients with advanced melanoma have also shown that elective discontinuation of anti-PD-1 therapy after treatment durations shorter than 24 months can be associated with durable off treatment survival. [11][12][13] In one study where patients with CR, PR, or SD electively discontinued anti-PD-1 therapy after a median of 12 months, the 1-year and 2-year PFS rates after discontinuation were 90% and 71%, respectively. 12 Patients with CR had a significantly lower risk of disease progression compared with patients with PR or SD.…”

Considerations for treatment duration in responders to immune checkpoint inhibitors

“…Of 52 patients who electively discontinued PD-1 inhibitors after 1 year (>6 months and <18 months) in the setting of ongoing treatment response or disease stability, after median follow-up of 20.5 months (range 3–49.2) from treatment discontinuation, 39 (75%) patients remained without disease progression (median PFS not reached). 4 …”

Discontinuation of anti‐PD‐1 monotherapy in advanced melanoma—Outcomes of daily clinical practice

“…The Checkmate‐153 showed that 1‐year fixed nivolumab treatment duration in non‐small cell lung cancer was associated with unfavourable outcomes 5 . For melanoma, the KEYNOTE‐001/006 trials and three observational studies showed high rates of ongoing responses after anti‐PD‐1 discontinuation 1,2,6‐10 . Factors associated with progression after discontinuation were PR and treatment duration of less than 6 months in patients with a CR who discontinued anti‐PD1 monotherapy early 8 .…”

“… 5 For melanoma, the KEYNOTE‐001/006 trials and three observational studies showed high rates of ongoing responses after anti‐PD‐1 discontinuation. 1 , 2 , 6 , 7 , 8 , 9 , 10 Factors associated with progression after discontinuation were PR and treatment duration of less than 6 months in patients with a CR who discontinued anti‐PD1 monotherapy early. 8 However, conditions for anti‐PD‐1 discontinuation were different between these studies and, therefore, evidence is fragmented.…”