- Email: [email protected]
BRCA1 expression level as prognostic factor for recurrence in resected NSCLC with adjuvant chemotherapy: SCAT Trial
Annals of Oncology 30 (Supplement 5): v585–v590, 2019 doi:10.1093/annonc/mdz258
NSCLC, EARLY STAGE 1439PD
BRCA1 expression level as prognostic factor for recurrence in resected NSCLC with adjuvant chemotherapy: SCAT Trial
Background: Post-operative platinum-based chemotherapy is the standard of care for resected NSCLC with nodal involvement. Expression of genes involved in DNA repair may have a prognostic role for the outcome. BRCA1 plays an important role in DNA repair pathways and could have a prognostic impact in this setting. The SCAT trial results found that for low BRCA1 levels subgroup Cis-Gem was superior to Cis-Doc and in high BRCA1 subgroup docetaxel single agent without platinum achieved similar survival to Cis-Doc. Risk of recurrence analysis according BRCA-1 levels has been performed. Methods: From Jun/2007 to May/2013 591 patients were screened and 500 were included, 108 in the control arm treated with Cis-Docetaxel and 392 in the experimental arms treated with Cis-Gem, Cis-Doc or docetaxel alone according to terciles of BRCA1 expression level. With a cut-off September 30th 2018 and a median follow-up of 60 months, recurrence patterns were analysed for the whole group according BRCA1 levels in tumor tissue and comparison were made for risk of recurrence, single/multiple recurrence, thoracic/extrathoracic and metastatic sites (liver, bone, brain). Results: Cumulative recurrence was evaluable in 232/456 patients (50.8%), 182/354 patients treated in the experimental arm and in 50/102 patients treated in the control arm (RR 1.04; 0.83-1.30) (p ¼ 0.672). The majority of recurrences 159/232 (68.5%) were single site intrathoracic recurrences in 121/232 (52%) while 111/232 were extrathoracic (47.8%). Overall recurrence was 56.5% (113/200 p) for low tercile BRCA1 vs 48.8% (63/129) for intermediate tercile vs 44% (56/127) for high tercile (p ¼ 0.025). No differences were seen between tercile groups for single site (p ¼ 0.35), multiple site (p ¼ 0.26), intrathoracic (p ¼ 0.36), or extrathoracic (p ¼ 0.38). More frequent distant metastatic sites were: bone (42 patients), brain (38 patients) and liver (11 patients). RIsk reduction was seen for brain metastases in patients with higher tercile BRCA1 (p ¼ 0.003). Conclusions: For NSCLC resected patients with lymph node involvement risk of recurrence remains high with a cumulative rate > 50%. Relative risk of recurrence was lower for tumors with higher BRCA1 levels. Distant metastases were seen in 47.8% of patients. Brain metastases risk was significant lower for patients with low BRCA1 expression. BRCA1 levels acts as a prognostic factor in early stages NSCLC. Clinical trial identification: EudraCT: 2007-000067-15; NCT 00478699. Legal entity responsible for the study: Spanish Lung Cancer Group - Grupo Espa~ nol Cancer de Pulm on. Funding: Sanofi Aventis. Disclosure: All authors have declared no conflicts of interest.
JIPANG study: Randomized phase III study of pemetrexed/cisplatin (PEM/Cis) versus vinorelbine /cisplatin (VNR/Cis) for completely resected p-stage II-IIIA non-squamous non-small cell lung cancer (Ns-NSCLC): Outcomes based on EGFR mutation status
M. Tsuboi1, H. Kenmotsu2, T. Yamanaka3, K. Yoshiya4, T. Takahashi5, T. Ueno6, K. Goto7, H. Daga8, N. Ikeda9, K. Sugio10, T. Seto11, S. Toyooka12, H. Date13, T. Mitsudomi14, I. Okamoto15, K. Yokoi16, H. Saka17, H. Okamoto18, Y. Takiguchi19, N. Yamamoto20 1 Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwa, Japan, 2Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi, Japan, 3 Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan, 4Chest surgery, Niigata Cancer Center Hospital, Niigata, Japan, 5Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan, 6Thoracic surgery, National Hospital Organization, Shikoku Cancer Center, Matsuyama, Japan, 7Thoracic oncology, National Cancer Center Hospital East, Kashiwa, Japan, 8Department of Medical Oncology, Osaka City General Hospital, Osaka, Japan, 9Department of Surgery, Tokyo Medical University, Tokyo, Japan, 10Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine, Yufu, Japan, 11Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan, 12General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University, Okayama, Japan, 13Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 14Surgery, KIndai University Faculty of Medicine, Osaka-Sayama, Japan, 15Research Institute for Disease of the Chest, Kyushu University Faculty of Medicine, Fukuoka, Japan, 16Thoracic Surgery, Nagoya University, Nagoya, Japan, 17Respiratory Medicine, National Hospital Organization Nagoya Medical Center, Nagoya, Japan, 18Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen’s Hospital, Yokohama, Japan, 19Department of Medical Oncology, Chiba University, Chiba, Japan, 20Internal Medicine and Medical Oncology, Wakayama Medical University, Wakayama, Japan Background: The VNR/Cis chemotherapy doublet has been evaluated in prior positive adjuvant trials in patients with completely resected Ns-NSCLC, whereas no phase III study has so far evaluated PEM/Cis in this population. And there are few data regarding outcomes based on EGFR mutation (EGFRm) status in adjuvant chemotherapies. Methods: Patients with completely resected Ns-NSCLC were randomized in a 1:1 ratio to receive either PEM (500 mg/m2, day 1)/Cis (75 mg/m2, day 1) or VNR (25 mg/m2, days 1 and 8)/Cis (80 mg/m2, day 1), and stratified according to sex, age, pathologic stage, EGFRm status and institution. The primary endpoint was recurrence-free survival (RFS), and, the planned sample size was 800 patients in total (Trial Identifier, UMIN000006737). Results: Between March 2012 and August 2016, 804 patients were randomized. Of 784 for the efficacy analysis (389 in PEM/Cis and 395 in VNR/Cis), median age was 65/65 years; stage IIIA 52.2%/52.4%; adenocarcinoma, 95.9%/95.9%; and EGFR mutation, 24.1%/24.9%. With a median follow-up of 45.2 months (mo), median RFS was 38.9mo in PEM/Cis and 37.3mo in VNR/Cis with a hazard ratio (HR) of 0.98 (95% CI, 0.81– 1.20; log-rank test, P ¼ 0.948), whereas HRs in patients with or without EGFRm were 1.38 (95% CI, 0.95–1.99) and 0.87 (95% CI, 0.69–1.09), respectively (Interaction, P ¼ 0.046). As for patients without EGFRm, median RFS was 65.2mo in PEM/Cis and 39.9mo in VNR/Cis. The overall survival rate at 3 years was 83.5% versus 87.2% with a HR of 0.98 (95% CI, 0.71 –1.35). Rates of treatment completion were 87.9% (PEM/Cis) and 72.7% (VNR/Cis), respectively (P < 0.001). Incidences of grade 3 or 4 febrile neutropenia (11.6/0.3%, P < 0.001), neutropenia (81.1/22.8%, P < 0.001), and anemia (9.3/2.8%, P < 0.001); any grade alopecia (30.1/12.8%, P < 0.001). Conclusions: Although this phase III study did not meet the primary endpoint, PEM/ CDDP had a similar efficacy to VNR/CDDP with a better tolerability as postoperative adjuvant chemotherapy for Ns-NSCLC patients. A significant interaction for RFS was found between treatment and EGFR mutation status. In patients without EGFR mutation, PEM/Cis seems to be a preferable regimen as the adjuvant chemotherapy. Clinical trial identification: UMIN000006737. Legal entity responsible for the study: The authors. Funding: Health and Labor Sciences Research Grants, The Japan Agency of Medical Research and Development (AMED). Disclosure: M. Tsuboi: Honoraria (self): AstraZeneca KK; Honoraria (self): Johnson & Johnson Japan; Honoraria (self): MSD; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self): Taiho Pharma; Honoraria (self): Eli Lilly Japan; Honoraria (self): Boehringer Ingelheim Japan; Honoraria (self): Ono Pharmaceutical Co., Ltd; Honoraria (self): Bristol-Myers Squibb KK; Honoraria (self): Daiichi-Sankyo; Honoraria (self): Covidien Japan; Honoraria (self): Teijin Pharma; Research grant / Funding (institution): Boehringer Ingelheim Japan. All other authors have declared no conflicts of interest.
C European Society for Medical Oncology 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V
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Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz258/5577210 by guest on 24 October 2019
B. Massuti Sureda1, J.M. Sanchez Torres2, M. Cobo Dols3, M.T. Moran Bueno4, J.L. Gonzalez-Larriba5, I.C. Barneto Aranda6, J. De Castro Carpeno7, L. Iglesias8, opez Vivanco10, M.D. Isla Casado11, R. L opez12, R. de las Penas M.A. Mu~ noz9, G. L Bataller13, D. Rodriguez Abreu14, A. Artal-Cortes15, E. Esteban16, M. Provencio17, E. Pereira18, J. Sanchez-Paya19, R. Rosell20 1 Department of Medical Oncology, Hospital General Universitario de Alicante, Alicante, Spain, 2Medical Oncology, Hospital Universitario de La Princesa, Madrid, Spain, 3 Medical Oncology, Hospital Regional Universitario de M alaga, M alaga, Spain, 4 Department of Medical Oncology, Catalan Institute of Oncology (ICO Badalona), 5 Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain, Department of Medical Oncology, Hospital Clinico Universitario San Carlos, Madrid, Spain, 6Department of Medical Oncology, University Hospital Reina Sofia, Cordoba, Spain, 7Medical Oncology, Hospital Universitario La Paz, Madrid, Spain, 8Oncology, University Hospital 12 de on Instituto Valenciano de Octubre, Madrid, Spain, 9Medical Oncology, IVO - Fundaci Oncologıa, Valencia, Spain, 10Medical Oncology, Hospital Universitario Cruces, 11 Barakaldo, Spain, Medical Oncology, Hospital Clinico Universitario Lozano Blesa, Zaragoza, Spain, 12Medical Oncology, Hospital Clınico Universitario de Santiago (CHUS), Santiago De Compostela, Spain, 13Medical Oncology, Hospital Provincial Castellon, Castellon, Spain, 14Medical Oncology, Hospital Universitario Insular de Gran Canaria, Las Palmas, Canary Islands, Spain, 15Department of Medical Oncology, Hospital Miguel Servet, Zaragoza, Spain, 16Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain, 17Medical Oncology, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain, 18Office Management, Spanish Lung Cancer Group Office, Barcelona, Spain, 19Epidemiology, ISABIAL, Alicante, Spain, 20Laboratory of Cellular and Molecular Biology, Institut for Healh Sciences Germans Trias i Pujol, Badalona, Spain
1440PD
NSCLC, EARLY STAGE 1439PD
BRCA1 expression level as prognostic factor for recurrence in resected NSCLC with adjuvant chemotherapy: SCAT Trial
Background: Post-operative platinum-based chemotherapy is the standard of care for resected NSCLC with nodal involvement. Expression of genes involved in DNA repair may have a prognostic role for the outcome. BRCA1 plays an important role in DNA repair pathways and could have a prognostic impact in this setting. The SCAT trial results found that for low BRCA1 levels subgroup Cis-Gem was superior to Cis-Doc and in high BRCA1 subgroup docetaxel single agent without platinum achieved similar survival to Cis-Doc. Risk of recurrence analysis according BRCA-1 levels has been performed. Methods: From Jun/2007 to May/2013 591 patients were screened and 500 were included, 108 in the control arm treated with Cis-Docetaxel and 392 in the experimental arms treated with Cis-Gem, Cis-Doc or docetaxel alone according to terciles of BRCA1 expression level. With a cut-off September 30th 2018 and a median follow-up of 60 months, recurrence patterns were analysed for the whole group according BRCA1 levels in tumor tissue and comparison were made for risk of recurrence, single/multiple recurrence, thoracic/extrathoracic and metastatic sites (liver, bone, brain). Results: Cumulative recurrence was evaluable in 232/456 patients (50.8%), 182/354 patients treated in the experimental arm and in 50/102 patients treated in the control arm (RR 1.04; 0.83-1.30) (p ¼ 0.672). The majority of recurrences 159/232 (68.5%) were single site intrathoracic recurrences in 121/232 (52%) while 111/232 were extrathoracic (47.8%). Overall recurrence was 56.5% (113/200 p) for low tercile BRCA1 vs 48.8% (63/129) for intermediate tercile vs 44% (56/127) for high tercile (p ¼ 0.025). No differences were seen between tercile groups for single site (p ¼ 0.35), multiple site (p ¼ 0.26), intrathoracic (p ¼ 0.36), or extrathoracic (p ¼ 0.38). More frequent distant metastatic sites were: bone (42 patients), brain (38 patients) and liver (11 patients). RIsk reduction was seen for brain metastases in patients with higher tercile BRCA1 (p ¼ 0.003). Conclusions: For NSCLC resected patients with lymph node involvement risk of recurrence remains high with a cumulative rate > 50%. Relative risk of recurrence was lower for tumors with higher BRCA1 levels. Distant metastases were seen in 47.8% of patients. Brain metastases risk was significant lower for patients with low BRCA1 expression. BRCA1 levels acts as a prognostic factor in early stages NSCLC. Clinical trial identification: EudraCT: 2007-000067-15; NCT 00478699. Legal entity responsible for the study: Spanish Lung Cancer Group - Grupo Espa~ nol Cancer de Pulm on. Funding: Sanofi Aventis. Disclosure: All authors have declared no conflicts of interest.
JIPANG study: Randomized phase III study of pemetrexed/cisplatin (PEM/Cis) versus vinorelbine /cisplatin (VNR/Cis) for completely resected p-stage II-IIIA non-squamous non-small cell lung cancer (Ns-NSCLC): Outcomes based on EGFR mutation status
M. Tsuboi1, H. Kenmotsu2, T. Yamanaka3, K. Yoshiya4, T. Takahashi5, T. Ueno6, K. Goto7, H. Daga8, N. Ikeda9, K. Sugio10, T. Seto11, S. Toyooka12, H. Date13, T. Mitsudomi14, I. Okamoto15, K. Yokoi16, H. Saka17, H. Okamoto18, Y. Takiguchi19, N. Yamamoto20 1 Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwa, Japan, 2Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi, Japan, 3 Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan, 4Chest surgery, Niigata Cancer Center Hospital, Niigata, Japan, 5Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan, 6Thoracic surgery, National Hospital Organization, Shikoku Cancer Center, Matsuyama, Japan, 7Thoracic oncology, National Cancer Center Hospital East, Kashiwa, Japan, 8Department of Medical Oncology, Osaka City General Hospital, Osaka, Japan, 9Department of Surgery, Tokyo Medical University, Tokyo, Japan, 10Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine, Yufu, Japan, 11Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan, 12General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University, Okayama, Japan, 13Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 14Surgery, KIndai University Faculty of Medicine, Osaka-Sayama, Japan, 15Research Institute for Disease of the Chest, Kyushu University Faculty of Medicine, Fukuoka, Japan, 16Thoracic Surgery, Nagoya University, Nagoya, Japan, 17Respiratory Medicine, National Hospital Organization Nagoya Medical Center, Nagoya, Japan, 18Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen’s Hospital, Yokohama, Japan, 19Department of Medical Oncology, Chiba University, Chiba, Japan, 20Internal Medicine and Medical Oncology, Wakayama Medical University, Wakayama, Japan Background: The VNR/Cis chemotherapy doublet has been evaluated in prior positive adjuvant trials in patients with completely resected Ns-NSCLC, whereas no phase III study has so far evaluated PEM/Cis in this population. And there are few data regarding outcomes based on EGFR mutation (EGFRm) status in adjuvant chemotherapies. Methods: Patients with completely resected Ns-NSCLC were randomized in a 1:1 ratio to receive either PEM (500 mg/m2, day 1)/Cis (75 mg/m2, day 1) or VNR (25 mg/m2, days 1 and 8)/Cis (80 mg/m2, day 1), and stratified according to sex, age, pathologic stage, EGFRm status and institution. The primary endpoint was recurrence-free survival (RFS), and, the planned sample size was 800 patients in total (Trial Identifier, UMIN000006737). Results: Between March 2012 and August 2016, 804 patients were randomized. Of 784 for the efficacy analysis (389 in PEM/Cis and 395 in VNR/Cis), median age was 65/65 years; stage IIIA 52.2%/52.4%; adenocarcinoma, 95.9%/95.9%; and EGFR mutation, 24.1%/24.9%. With a median follow-up of 45.2 months (mo), median RFS was 38.9mo in PEM/Cis and 37.3mo in VNR/Cis with a hazard ratio (HR) of 0.98 (95% CI, 0.81– 1.20; log-rank test, P ¼ 0.948), whereas HRs in patients with or without EGFRm were 1.38 (95% CI, 0.95–1.99) and 0.87 (95% CI, 0.69–1.09), respectively (Interaction, P ¼ 0.046). As for patients without EGFRm, median RFS was 65.2mo in PEM/Cis and 39.9mo in VNR/Cis. The overall survival rate at 3 years was 83.5% versus 87.2% with a HR of 0.98 (95% CI, 0.71 –1.35). Rates of treatment completion were 87.9% (PEM/Cis) and 72.7% (VNR/Cis), respectively (P < 0.001). Incidences of grade 3 or 4 febrile neutropenia (11.6/0.3%, P < 0.001), neutropenia (81.1/22.8%, P < 0.001), and anemia (9.3/2.8%, P < 0.001); any grade alopecia (30.1/12.8%, P < 0.001). Conclusions: Although this phase III study did not meet the primary endpoint, PEM/ CDDP had a similar efficacy to VNR/CDDP with a better tolerability as postoperative adjuvant chemotherapy for Ns-NSCLC patients. A significant interaction for RFS was found between treatment and EGFR mutation status. In patients without EGFR mutation, PEM/Cis seems to be a preferable regimen as the adjuvant chemotherapy. Clinical trial identification: UMIN000006737. Legal entity responsible for the study: The authors. Funding: Health and Labor Sciences Research Grants, The Japan Agency of Medical Research and Development (AMED). Disclosure: M. Tsuboi: Honoraria (self): AstraZeneca KK; Honoraria (self): Johnson & Johnson Japan; Honoraria (self): MSD; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self): Taiho Pharma; Honoraria (self): Eli Lilly Japan; Honoraria (self): Boehringer Ingelheim Japan; Honoraria (self): Ono Pharmaceutical Co., Ltd; Honoraria (self): Bristol-Myers Squibb KK; Honoraria (self): Daiichi-Sankyo; Honoraria (self): Covidien Japan; Honoraria (self): Teijin Pharma; Research grant / Funding (institution): Boehringer Ingelheim Japan. All other authors have declared no conflicts of interest.
C European Society for Medical Oncology 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V
All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz258/5577210 by guest on 24 October 2019
B. Massuti Sureda1, J.M. Sanchez Torres2, M. Cobo Dols3, M.T. Moran Bueno4, J.L. Gonzalez-Larriba5, I.C. Barneto Aranda6, J. De Castro Carpeno7, L. Iglesias8, opez Vivanco10, M.D. Isla Casado11, R. L opez12, R. de las Penas M.A. Mu~ noz9, G. L Bataller13, D. Rodriguez Abreu14, A. Artal-Cortes15, E. Esteban16, M. Provencio17, E. Pereira18, J. Sanchez-Paya19, R. Rosell20 1 Department of Medical Oncology, Hospital General Universitario de Alicante, Alicante, Spain, 2Medical Oncology, Hospital Universitario de La Princesa, Madrid, Spain, 3 Medical Oncology, Hospital Regional Universitario de M alaga, M alaga, Spain, 4 Department of Medical Oncology, Catalan Institute of Oncology (ICO Badalona), 5 Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain, Department of Medical Oncology, Hospital Clinico Universitario San Carlos, Madrid, Spain, 6Department of Medical Oncology, University Hospital Reina Sofia, Cordoba, Spain, 7Medical Oncology, Hospital Universitario La Paz, Madrid, Spain, 8Oncology, University Hospital 12 de on Instituto Valenciano de Octubre, Madrid, Spain, 9Medical Oncology, IVO - Fundaci Oncologıa, Valencia, Spain, 10Medical Oncology, Hospital Universitario Cruces, 11 Barakaldo, Spain, Medical Oncology, Hospital Clinico Universitario Lozano Blesa, Zaragoza, Spain, 12Medical Oncology, Hospital Clınico Universitario de Santiago (CHUS), Santiago De Compostela, Spain, 13Medical Oncology, Hospital Provincial Castellon, Castellon, Spain, 14Medical Oncology, Hospital Universitario Insular de Gran Canaria, Las Palmas, Canary Islands, Spain, 15Department of Medical Oncology, Hospital Miguel Servet, Zaragoza, Spain, 16Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain, 17Medical Oncology, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain, 18Office Management, Spanish Lung Cancer Group Office, Barcelona, Spain, 19Epidemiology, ISABIAL, Alicante, Spain, 20Laboratory of Cellular and Molecular Biology, Institut for Healh Sciences Germans Trias i Pujol, Badalona, Spain
1440PD