Long‐term outcomes in patients with advanced and/or metastatic non–small cell lung cancer who completed 2 years of immune checkpoint inhibitors or achieved a durable response after discontinuation without disease progression: Multicenter, real‐world data (KCSG LU20‐11)

Abstract

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown significant improvements in patients with advanced non-small cell lung cancer (NSCLC). One of the major issues with ICIs is determining the optimal treatment duration. METHODS: This multicenter, retrospective study analyzed clinical outcomes in patients with NSCLC who completed 2 years of ICI therapy or were treated for more than 6 months and then discontinued ICIs without disease progression at 11 medical centers in Korea between August 2017 and December 2020. RESULTS: Ninety-six patients who completed 2 years of ICIs were reviewed. The median durations of treatment and follow-up were 24.0 and 33.9 months, respectively. The objective response rate (ORR) was 85.4%. The median progression-free survival (PFS) and overall survival (OS) periods were not reached. After completion, the PFS and OS rates were 81.1% and 96.4%, respectively, at 12 months. Forty-three patients were identified who discontinued ICIs without disease progression: 26 (60.5%) for adverse events and 17 (39.5%) for other causes. The median durations of treatment and follow-up were 10.5 and 21.2 months, respectively. The ORR was 90.7%. The median PFS and OS periods were not reached. After discontinuation, the PFS and OS rates were 71.0% and 90.0%, respectively, at 12 months. CONCLUSIONS: A significantly high proportion of patients who completed 2 years of ICI therapy continued to experience long-term PFS. Even if ICIs are discontinued after 6 months in patients without disease progression, they may achieve a durable response and facilitate long-term survival.

Circulating Tumor DNA Monitoring Reveals Molecular Progression before Radiologic Progression in a Real-life Cohort of Patients with Advanced Non–small Cell Lung Cancer

“…Furthermore, we would propose discontinuation of immunotherapy before the standard 2 years of treatment, if ctDNA measurements reach the limit of detection, based on the certain ctDNA response we observed in all long-term responders. Thereby, it would be possible to explore the optimal duration of immunotherapy, as empasized in recent studies ( 55–57 ). A noninferiority study design is required with primary endpoint being OS—and secondary endpoints being PFS by radiologic evaluation and by ctDNA measurements, number of treatment cycles, adverse events, and quality of life.…”

Dosing Regimens of Immune Checkpoint Inhibitors: Attempts at Lower Dose, Less Frequency, Shorter Course

“…Further stratified analysis showed that CR/PR patients is benefit from continuous treatment, while for SD patients, the median PFS of continuous treatment and 1-year fixed treatment was similar, suggesting that continued treatment was more meaningful for CR/PR patients ( 118 ). A multicenter retrospective study from Korea reported the long-term follow-up results in patients with advanced and/or metastatic NSCLC ( 119 ). For patients who completed 2-years ICIs therapy, the 1-year PFS and OS were 81.1% and 96.4%, respectively.…”

“…And for patients who discontinued ICIs after more than 6 months of treatment without disease progression, the 1-year PFS and OS were 71.0% and 90.0%, respectively. Among them, the risk of relapse was significantly higher for treatment duration of 6-12 months but did not differ between 12-18 or 18-24 months ( 119 ). Bilger reported that NSCLC patients who chose to discontinue the drug after at least 18 months of ICIs therapy had 1-year PFS and OS of 71% and 90%, and 2-year PFS and OS of 63% and 84%, respectively ( 120 ).…”

What is the optimal duration of immune checkpoint inhibitors in malignant tumors?

“…It was found that a significantly high proportion of patients who completed 2 years of ICIs therapy continued to experience long-term PFS. Even if ICIs were discontinued in patients without disease progression after 6 months administration, they might achieve a durable response and facilitate long-term survival ( 48 ). In an observational cohort study, 52 patients with metastatic melanoma who discontinued anti-PD-1 therapy after one year remained free of disease progression in the long-term follow-up, and the risk of disease progression was low even in patients with remnant lesions by imaging ( 49 ).…”