The efficacy and safety of chemo‐free therapy in epidermal growth factor receptor tyrosine kinase inhibitor‐resistant advanced non‐small cell lung cancer: A single‐arm, phase II study
Abstract Objectives The purpose of this study was to explore the efficacy and safety of toripalimab combined with anlotinib in patients with advanced non‐small cell lung cancer (NSCLC) who acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs). Materials and M...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-10-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.6545 |
| _version_ | 1797654505997729792 |
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| author | Shuyang Zhang Lu Yang Yaning Yang Guangjian Yang Haiyan Xu Xueliang Niu Yan Wang |
| author_facet | Shuyang Zhang Lu Yang Yaning Yang Guangjian Yang Haiyan Xu Xueliang Niu Yan Wang |
| author_sort | Shuyang Zhang |
| collection | DOAJ |
| description | Abstract Objectives The purpose of this study was to explore the efficacy and safety of toripalimab combined with anlotinib in patients with advanced non‐small cell lung cancer (NSCLC) who acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs). Materials and Methods Patients who developed resistance after using first‐ or second‐generation EGFR‐TKIs as their first‐line regimen without EGFR T790M mutation or had disease progression after being treated with third‐generation EGFR‐TKIs as first‐ or second‐line therapy were enrolled. All patients received toripalimab (240 mg/day on Day 1, intravenously) combined with anlotinib (12 mg/day, Days 1–14, orally) once every 3 weeks. Treatment continued until disease progression, or if toxicity was intolerable. The primary endpoint was the objective response rate (ORR) assessed by the investigator. The secondary endpoint was the progression‐free survival (PFS). Results In total, 19 patients were enrolled between May 2020 and October 2021.The ORR was 0%, and a median PFS was 2.1 months (95% CI 0.251–3.949). Grade ≥3 treatment‐related adverse events (AEs) occurred in 11% patients. Common adverse events included hypothyroidism (12/19), fatigue (9/19), and hypertension (8/19). Patients in stable disease (SD) group had lower abundance of EGFR mutation allele frequency (AF) before enrollment than those in progressive disease (PD) group (p = 0.031). Patients without detectable EGFR mutation (EGFR−) had longer PFS compared to the ones with EGFR mutations (p = 0.059). Patients with high levels of soluble programmed cell death ligand 1 (PD‐L1) at baseline also tended to have longer PFS (p = 0.160). Conclusion Toripalimab combined with anlotinib was tolerable in EGFR‐TKI‐resistant advanced NSCLC patients not previously treated with chemotherapy. Patients without detectable EGFR mutation and high soluble PD‐L1 levels may benefit from this chemotherapy‐free treatment. |
| first_indexed | 2024-03-11T17:00:27Z |
| format | Article |
| id | doaj.art-8d290b90eb984770bc5c99d738ee84a5 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-11T17:00:27Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-8d290b90eb984770bc5c99d738ee84a52023-10-20T10:25:44ZengWileyCancer Medicine2045-76342023-10-011219194381944810.1002/cam4.6545The efficacy and safety of chemo‐free therapy in epidermal growth factor receptor tyrosine kinase inhibitor‐resistant advanced non‐small cell lung cancer: A single‐arm, phase II studyShuyang Zhang0Lu Yang1Yaning Yang2Guangjian Yang3Haiyan Xu4Xueliang Niu5Yan Wang6Cancer Center, Beijing Tongren Hospital Capital Medical University Beijing ChinaDepartment of Medical Oncology and Radiation Sickness Peking University Third Hospital Beijing ChinaDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Respiratory Medicine, Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences Jinan ChinaDepartment of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Medical Affairs Shanghai Junshi Biosciences Co., Ltd. Shanghai ChinaDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaAbstract Objectives The purpose of this study was to explore the efficacy and safety of toripalimab combined with anlotinib in patients with advanced non‐small cell lung cancer (NSCLC) who acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs). Materials and Methods Patients who developed resistance after using first‐ or second‐generation EGFR‐TKIs as their first‐line regimen without EGFR T790M mutation or had disease progression after being treated with third‐generation EGFR‐TKIs as first‐ or second‐line therapy were enrolled. All patients received toripalimab (240 mg/day on Day 1, intravenously) combined with anlotinib (12 mg/day, Days 1–14, orally) once every 3 weeks. Treatment continued until disease progression, or if toxicity was intolerable. The primary endpoint was the objective response rate (ORR) assessed by the investigator. The secondary endpoint was the progression‐free survival (PFS). Results In total, 19 patients were enrolled between May 2020 and October 2021.The ORR was 0%, and a median PFS was 2.1 months (95% CI 0.251–3.949). Grade ≥3 treatment‐related adverse events (AEs) occurred in 11% patients. Common adverse events included hypothyroidism (12/19), fatigue (9/19), and hypertension (8/19). Patients in stable disease (SD) group had lower abundance of EGFR mutation allele frequency (AF) before enrollment than those in progressive disease (PD) group (p = 0.031). Patients without detectable EGFR mutation (EGFR−) had longer PFS compared to the ones with EGFR mutations (p = 0.059). Patients with high levels of soluble programmed cell death ligand 1 (PD‐L1) at baseline also tended to have longer PFS (p = 0.160). Conclusion Toripalimab combined with anlotinib was tolerable in EGFR‐TKI‐resistant advanced NSCLC patients not previously treated with chemotherapy. Patients without detectable EGFR mutation and high soluble PD‐L1 levels may benefit from this chemotherapy‐free treatment.https://doi.org/10.1002/cam4.6545antiangiogenic agentschemo‐free therapyEGFR gene mutationimmune checkpoint inhibitorsnon‐small cell lung cancer |
| spellingShingle | Shuyang Zhang Lu Yang Yaning Yang Guangjian Yang Haiyan Xu Xueliang Niu Yan Wang The efficacy and safety of chemo‐free therapy in epidermal growth factor receptor tyrosine kinase inhibitor‐resistant advanced non‐small cell lung cancer: A single‐arm, phase II study Cancer Medicine antiangiogenic agents chemo‐free therapy EGFR gene mutation immune checkpoint inhibitors non‐small cell lung cancer |
| title | The efficacy and safety of chemo‐free therapy in epidermal growth factor receptor tyrosine kinase inhibitor‐resistant advanced non‐small cell lung cancer: A single‐arm, phase II study |
| title_full | The efficacy and safety of chemo‐free therapy in epidermal growth factor receptor tyrosine kinase inhibitor‐resistant advanced non‐small cell lung cancer: A single‐arm, phase II study |
| title_fullStr | The efficacy and safety of chemo‐free therapy in epidermal growth factor receptor tyrosine kinase inhibitor‐resistant advanced non‐small cell lung cancer: A single‐arm, phase II study |
| title_full_unstemmed | The efficacy and safety of chemo‐free therapy in epidermal growth factor receptor tyrosine kinase inhibitor‐resistant advanced non‐small cell lung cancer: A single‐arm, phase II study |
| title_short | The efficacy and safety of chemo‐free therapy in epidermal growth factor receptor tyrosine kinase inhibitor‐resistant advanced non‐small cell lung cancer: A single‐arm, phase II study |
| title_sort | efficacy and safety of chemo free therapy in epidermal growth factor receptor tyrosine kinase inhibitor resistant advanced non small cell lung cancer a single arm phase ii study |
| topic | antiangiogenic agents chemo‐free therapy EGFR gene mutation immune checkpoint inhibitors non‐small cell lung cancer |
| url | https://doi.org/10.1002/cam4.6545 |
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