Cancer. 2022;128(4):778-787.

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).

, , , , , , , , , , , ,

제1저자 김홍식, 김동완 · 교신저자 안명주

PMID 34705268 PMC9297884 DOI 10.1002/cncr.33984 IF 5.6 혈액종양내과

소속 (11)

Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea.
Division of Hematology-Oncology, Department of Medicine, National Cancer Center, Goyang, Republic of Korea.
Division of Medical Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea.
Division of Oncology, Department of Internal Medicine, Incheon St. Mary's Hospital, Catholic University of Korea, Incheon, Republic of Korea.
Division of Oncology, Department of Internal Medicine, Inje University College of Medicine, Haeundae-Paik Hospital, Busan, Korea.
Division of Hematology-Oncology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Division of Hematology-Oncology, Department of Medicine, Kosin University Gospel Hospital, Busan, Republic of Korea.
Division of Hematology-Oncology, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
Division of Hematology-Oncology, Department of Internal Medicine, Yeungnam University Medical Center, Daegu, Republic of Korea.
Division of Hemato-Oncology, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea.

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.

LAY SUMMARY The optimal treatment duration for immune checkpoint inhibitors (ICIs) remains to be determined. This study reports the long-term outcomes of patients with non-small cell lung cancer who completed 2 years of ICI therapy or achieved a durable response after the discontinuation of ICIs without disease progression in real-world practice. A significantly high proportion of patients who completed 2 years of ICIs continued to experience long-term progression-free survival. In addition, even if ICIs are discontinued after 6 months in patients without disease progression, they may achieve a durable response and facilitate long-term survival.

Keywords

discontinuationduration of treatmentimmune checkpoint inhibitorimmunotherapylong-term survivalnon-small cell lung cancer

Figures

**Figure 1** Swimmer plots indicating the duration of ICI treatment and follow‐up, progression‐free survival, and overall survival for patients who (A) completed 2 years of ICI therapy and (B) discontinued ICIs without disease progression. The light red bars indicate the duration of ICI treatment, the light teal bars indicate the follow‐up duration, and the light yellow bars indicate the time from the discontinuation of ICIs to disease progression. CR indicates complete response; ICI, immune checkpoint inhibitor; PD, progressive disease; PR, partial response; SD, stable disease.

**Figure 2** Kaplan‐Meier curves of a survival analysis of patients who completed 2 years of ICI therapy: (A) OS, (B) PFS, (C) PFS according to the response to treatment, and (D) PFS according to the line of treatment. CR indicates complete response; ICI, immune checkpoint inhibitor; OS, overall survival; PFS, progression‐free survival; PR, partial response; SD, stable disease.

**Figure 3** Kaplan‐Meier curves of a survival analysis of patients who discontinued ICIs without disease progression: (A) OS, (B) PFS, (C) PFS according to the response to treatment, (D) OS according to the response to treatment, (E) PFS according to the cause of treatment discontinuation, and (F) PFS according to the duration of treatment. CI indicates confidence interval; CR, complete response; ICI, immune checkpoint inhibitor; OS, overall survival; PFS, progression‐free survival; PR, partial response; SD, stable disease.

**Figure 4** Kaplan‐Meier curves of a survival analysis from treatment discontinuation in patients who discontinued ICIs without disease progression: (A) PFS according to the response to treatment, (B) OS according to the response to treatment, (C) PFS according to the cause of treatment discontinuation, and (D) OS according to the cause of treatment discontinuation. CR indicates complete response; ICI, immune checkpoint inhibitor; OS, overall survival; PFS, progression‐free survival; PR, partial response; SD, stable disease.

그림 출처: PubMed Central 공개 논문 (PMC9297884)

Conflict of interest statement

Dong‐Wan Kim reports research funding from Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer‐Ingelheim, Daiichi‐Sankyo, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan, Chong Keun Dang, Bridge BioTherapeutics, and GSK and travel and accommodation support for advisory board meeting attendance from Amgen and Daiichi‐Sankyo. Youngjoo Lee reports participation on boards for Roche Korea and Yuhan Corporation. Hee Kyung Ahn reports payments or honoraria from Yuhan, BMS, MSD, AstraZeneca, Roche, Lilly, Pfizer, and Menarini. Myung‐Ju Ahn reports consulting fees from Alpha Pharmaceuticals and payments or honoraria from MSD, Merck, Lilly, AstraZeneca, Takeda, Yuhan, and Roche. The other authors made no disclosures.

그 밖의 정보