Hye-Ryoun Kim1, Jae Chol Lee2, Young-Chul Kim3, Kyu-Sik Kim3, In-Jae Oh3, Sung Yong Lee4, Tae Won Jang5, Min Ki Lee6, Kyeong-Cheol Shin7, Gwan Ho Lee7, Jeong-Seon Ryu8, Seung Hoon Jang9, Ji Woong Son10, Jeong Eun Lee11, Sun Young Kim11, Hee Joung Kim12, Kye Young Lee13. 1. Department of Internal Medicine, Korea Cancer Center Hospital, 215-4, Gongneung-dong, Nowon-gu, Seoul 139-706, Republic of Korea. 2. Department of Oncology, Asan Medical Center, Ulsan University College of Medicine, Seoul, Republic of Korea. 3. Department of Internal Medicine, Chonnam National University College of Medicine, Hwasun Hospital, Hwasun, Republic of Korea. 4. Department of Internal Medicine, Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea. 5. Department of Internal Medicine, Kosin University College of Medicine, Pusan, Republic of Korea. 6. Department of Internal Medicine, Pusan National University College of Medicine, Pusan, Republic of Korea. 7. Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea. 8. Department of Internal Medicine, Inha University College of Medicine, Incheon, Republic of Korea. 9. Department of Internal Medicine, Hallym University College of Medicine, Anyang, Republic of Korea. 10. Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Republic of Korea. 11. Department of Internal Medicine, Chungnam National University College of Medicine, Deajeon, Republic of Korea. 12. Department of Internal Medicine, Konkuk University College of Medicine, Seoul, Republic of Korea. 13. Department of Internal Medicine, Konkuk University College of Medicine, Seoul, Republic of Korea. Electronic address: kyleemd@kuh.ac.kr.
Abstract
BACKGROUND: The NSCLC patients who experienced good clinical responses to an EGFR-TKI will inevitably develop acquired resistance. A great deal of research is being carried out to discover the molecular mechanisms underlying this resistance. In comparison, few studies have been conducted to find out about the clinical characteristics of acquired resistance in the patients who had responded to an EGFR-TKI. Herein we investigated clinical characteristics of NSCLC patients who experienced acquired resistance during gefitinib therapy. PATIENTS AND METHODS: We reviewed NSCLC patients who showed a clinical benefit from initial gefitinib therapy. All clinical data were obtained from 11 centers of Korean Molecular Lung Cancer Group (KMLCG). The clinical manifestations of acquired resistance, time to progression (TTP), and post-progression survival (PPS) after gefitinib failure were analyzed retrospectively. RESULTS: A total of 417 patients were recruited. Median TTP was 10.2 months (95% CI, 9.5-10.9). TTP showed a significant longer duration in female, non-smoker, and patients with adenocarcinoma. At the time of acquired resistance, 63.3% of the patients showed symptomatic deterioration. Sites of disease progression were as follows: primary lung lesion in 58.4%, previous metastasis in 38.3%, and new metastasis in 54.2%. Patients with EGFR wild type showed a tendency of higher frequency in symptomatic deterioration and newly development of CNS metastasis compared with patients with EGFR mutation. There was a significant difference in newly development of lung metastasis between patients with exon 19 deletion and those with L858R mutation (41.4% vs. 6.3%, p=0.02). PPS was 8.9 months (95% CI, 7.4-10.4). Smoking history, PS, new CNS lesion and subsequent chemotherapy were independent factors for PPS. CONCLUSION: This study suggests that clinical manifestations of acquired resistance may be different according to EGFR mutation status and EGFR mutation genotype. In addition, subsequent chemotherapy confers clinical benefit in terms of PPS in NSCLC patients who experienced acquired resistance after gefitinib therapy.
BACKGROUND: The NSCLCpatients who experienced good clinical responses to an EGFR-TKI will inevitably develop acquired resistance. A great deal of research is being carried out to discover the molecular mechanisms underlying this resistance. In comparison, few studies have been conducted to find out about the clinical characteristics of acquired resistance in the patients who had responded to an EGFR-TKI. Herein we investigated clinical characteristics of NSCLCpatients who experienced acquired resistance during gefitinib therapy. PATIENTS AND METHODS: We reviewed NSCLCpatients who showed a clinical benefit from initial gefitinib therapy. All clinical data were obtained from 11 centers of Korean Molecular Lung Cancer Group (KMLCG). The clinical manifestations of acquired resistance, time to progression (TTP), and post-progression survival (PPS) after gefitinib failure were analyzed retrospectively. RESULTS: A total of 417 patients were recruited. Median TTP was 10.2 months (95% CI, 9.5-10.9). TTP showed a significant longer duration in female, non-smoker, and patients with adenocarcinoma. At the time of acquired resistance, 63.3% of the patients showed symptomatic deterioration. Sites of disease progression were as follows: primary lung lesion in 58.4%, previous metastasis in 38.3%, and new metastasis in 54.2%. Patients with EGFR wild type showed a tendency of higher frequency in symptomatic deterioration and newly development of CNS metastasis compared with patients with EGFR mutation. There was a significant difference in newly development of lung metastasis between patients with exon 19 deletion and those with L858R mutation (41.4% vs. 6.3%, p=0.02). PPS was 8.9 months (95% CI, 7.4-10.4). Smoking history, PS, new CNS lesion and subsequent chemotherapy were independent factors for PPS. CONCLUSION: This study suggests that clinical manifestations of acquired resistance may be different according to EGFR mutation status and EGFR mutation genotype. In addition, subsequent chemotherapy confers clinical benefit in terms of PPS in NSCLCpatients who experienced acquired resistance after gefitinib therapy.
Authors: J B Auliac; C Fournier; C Audigier Valette; M Perol; A Bizieux; F Vinas; C Decroisette Phan van Ho; S Bota Ouchlif; R Corre; G Le Garff; P Fournel; N Baize; R Lamy; A Vergnenegre; D Arpin; B Marin; C Chouaid; R Gervais Journal: Target Oncol Date: 2016-04 Impact factor: 4.493