Rechallenge with Anti-PD-1 Inhibitors in Patients with Recurrent Gynecologic Malignancies
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: We investigated the treatment outcomes of immune checkpoint inhibitor (ICI) rechallenge in patients with recurrent gynecologic cancers. Materials and Methods: We retrospectively reviewed the medical records of 20 patients who underwent rechallenge with PD-1 inhibitors for recurrent gynecologic cancers at two tertiary centers between January 2018 and September 2022. Results: The median age of the patients was 56 years (range, 35–79). Seven (35%), 1 (5%), 11 (55%), and 1 (5%) patients presented with cervical, vulvar, ovarian, and endometrial cancers, respectively. Sixteen (80%) patients received pembrolizumab and 4 (20%) received nivolumab at first treatment. Eight (40%) and 12 (60%) patients received pembrolizumab and nivolumab, respectively, at second treatment. At initial ICI treatment, 1 (5%) and 4 (20%) cases of a complete response (CR) and a partial response (PR) were observed, respectively, with a median progression-free survival (PFS) of 2.8 months (range, 1.4–49.6). Reasons for first ICI discon tinuation were disease progression (n=16), severe adverse events (AEs) (n=2), and treatment withdrawal (n=2). During second ICI treatment, 1 (5%) patient achieved CR, 2 (10%) showed PR, and 5 (25%) experienced stable disease. The median PFS to second ICI was 1.8 months (range, 0.4–10.4). The median overall survival was 21.3 months (range, 10.1–52.7). Neither patient who dis continued ICI treatment due to AEs experienced AE relapse during second ICI treatment. Conclusion: These results suggest that responses to ICI rechallenge are not as intolerable as responses to previous ICI. Clinicians should carefully consider rechallenge with PD-1 inhibitors outside of clinical trials until there are sufficient data to routinely sup port this practice.
Abstract
Purpose: We investigated the treatment outcomes of immune checkpoint inhibitor (ICI) rechallenge in patients with recurrent gynecologic cancers. Materials and Methods: We retrospectively reviewed the medical records of 20 patients who underwent rechallenge with PD-1 inhibitors for recurrent gynecologic cancers at two tertiary centers between January 2018 and September 2022. Results: The median age of the patients was 56 years (range, 35–79). Seven (35%), 1 (5%), 11 (55%), and 1 (5%) patients presented with cervical, vulvar, ovarian, and endometrial cancers, respectively. Sixteen (80%) patients received pembrolizumab and 4 (20%) received nivolumab at first treatment. Eight (40%) and 12 (60%) patients received pembrolizumab and nivolumab, respectively, at second treatment. At initial ICI treatment, 1 (5%) and 4 (20%) cases of a complete response (CR) and a partial response (PR) were observed, respectively, with a median progression-free survival (PFS) of 2.8 months (range, 1.4–49.6). Reasons for first ICI discon tinuation were disease progression (n=16), severe adverse events (AEs) (n=2), and treatment withdrawal (n=2). During second ICI treatment, 1 (5%) patient achieved CR, 2 (10%) showed PR, and 5 (25%) experienced stable disease. The median PFS to second ICI was 1.8 months (range, 0.4–10.4). The median overall survival was 21.3 months (range, 10.1–52.7). Neither patient who dis continued ICI treatment due to AEs experienced AE relapse during second ICI treatment. Conclusion: These results suggest that responses to ICI rechallenge are not as intolerable as responses to previous ICI. Clinicians should carefully consider rechallenge with PD-1 inhibitors outside of clinical trials until there are sufficient data to routinely sup port this practice.
참고문헌 (19)
- Hargadon KM, "Immune checkpoint blockade therapy for cancer : an overview of FDA-approved immune checkpoint inhibitors", Int Immunopharmacol, 62, pp.29~39 (2018)
- Postow MA, "Immune checkpoint blockade in cancer therapy", J Clin Oncol, 33, pp.1974~1982 (2015)
- Motzer RJ, "Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma", N Engl J Med, 378, pp.1277~1290 (2018)
- Antonia SJ, "Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer(CheckMate 032) : a multicentre, openlabel, phase 1", 2 trial, 2016, pp.17, 883~895
- Metro G, "Immune checkpoints inhibitors rechallenge in non-small-cell lung cancer: different scenarios with different solutions?", Lung Cancer Manag, 8, pp.LMT18~ (2020)
- Schoenfeld AJ, "Acquired resistance to immune checkpoint inhibitors", Cancer Cell, 37, pp.443~455 (2020)
- Inno A, "Pathogenesis, clinical manifestations and management of immune checkpoint inhibitors toxicity", Tumori, 103, pp.405~421 (2017)
- Nakajima EC, "Challenge of rechallenge : when to resume immunotherapy following an immune-related adverse event", J Clin Oncol, 37, pp.2714~2718 (2019)
- Herbst RS, "Long-term outcomes and retreatment among patients with previously treated, programmed death-ligand 1-positive, advanced non-small-cell lung cancer in the KEYNOTE-010 study", J Clin Oncol, 38, pp.1580~1590 (2020)
- Inno A, "Rechallenge of immune checkpoint inhibitors : a systematic review and meta-analysis", Crit Rev Oncol Hematol, 165, pp.103434~ (2021)
- Drakes ML, "Immune checkpoint blockade in gynecologic cancers: state of affairs", Cancers(Basel), 12, pp.3301~ (2020)
- Joseph J. Noh, "Frequency of Mismatch Repair Deficiency", High Microsatellite Instability and Its Role as a Predictive Biomarker of Response to Immune Checkpoint Inhibitors in Gynecologic Cancers, 2022, pp.54(4), 1200~1208[DOI]
- Dolladille C, "Immune checkpoint inhibitor rechallenge after immune-related adverse events in patients with cancer", JAMA Oncol, 6, pp.865~871 (2020)
- Le DT, "PD-1 blockade in tumors with mismatch-repair deficiency", N Engl J Med, 372, pp.2509~2520 (2015)
- Marabelle A, "Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability", mismatch repair–deficient cancer : results from the phase II KEYNOTE-158 study, 2020, pp.38, 1~10
- Petrelli F, "Outcomes following immune checkpoint inhibitor treatment of patients with microsatellite instability-high cancers : a systematic review and metaanalysis", JAMA Oncol, 6, pp.1068~1071 (2020)
- Atrash S, "Response of metastatic mucosal melanoma to immunotherapy : it can get worse before it gets better", J Oncol Pharm Pract, 23, pp.215~219 (2017)
- Fessas P, "A molecular and preclinical comparison of the PD-1-targeted T-cell checkpoint inhibitors nivolumab and pembrolizumab", Semin Oncol, 44, pp.136~140 (2017)
- 최민철, "Real-World Experience with Pembrolizumab Treatment in Patients with Heavily Treated Recurrent Gynecologic Malignancies", Yonsei Medical Journal, 61(10), pp.844~850 (2020), 연세대학교의과대학[DOI]