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Poster display session

4848 - Subsequent therapies post-afatinib among patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC in LUX-Lung (LL) 3, 6 and 7


09 Sep 2017


Poster display session


Cytotoxic Therapy;  Cancers in Adolescents and Young Adults (AYA);  Non-Small Cell Lung Cancer


Lecia Sequist


Annals of Oncology (2017) 28 (suppl_5): v460-v496. 10.1093/annonc/mdx380


L. Sequist1, Y. Wu2, M. Schuler3, T. Kato4, J.C. Yang5, H. Tanaka6, T. Hida7, S. Lu8, K. Park9, S. Laurie10, J. Bennouna11, D. Moro Sibilot12, A. Märten13, B. Peil14, E. Ehrnrooth15, N. Yamamoto16, K. Nakagawa17

Author affiliations

  • 1 Hematology/oncology, Massachusetts General Hospital and Harvard Medical School, 02114 - Boston/US
  • 2 Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou/CN
  • 3 West German Cancer Center, University Hospital Essen, Essen/DE
  • 4 Department Of Thoracic Oncology, Kanagawa Cancer Center, Yokohama/JP
  • 5 Department Of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei/TW
  • 6 Department Of Internal Medicine, Niigata Cancer Center Hospital, Niigata/JP
  • 7 Department Of Thoracic Oncology, Aichi Cancer Center, Nagoya/JP
  • 8 Department Of Lung Cancer, Shanghai Chest Hospital, Shanghai/CN
  • 9 Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul/KR
  • 10 Division Of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottowa/CA
  • 11 Department Of Thoracic Oncology, Institut de Cancérologie de l'Ouest, Nantes/FR
  • 12 Department Of Medical Oncology, Centre Hospitalier Universitaire de Grenoble, Grenoble/FR
  • 13 Global Medicine, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein/DE
  • 14 N/a, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein/DE
  • 15 Ta Oncology, Boehringer Ingelheim, Danmark A/S, Copenhagen/DK
  • 16 Department Of Internal Medicine, Wakayama Medical University, Wakayama/JP
  • 17 Department Of Medical Oncology, Kinki University School of Medicine, Osaka/JP


Abstract 4848


Acquired resistance after front-line treatment (tx) with 1st-/2nd-generation EGFR TKIs necessitates further therapies for pts with EGFRm+ NSCLC. We explored the outcome of subsequent therapies, including other EGFR TKIs and chemotherapy (CT) after 1st-line afatinib in the LL3, 6 and 7 randomised trials.


We retrospectively assessed subsequent therapy outcomes in pts with common EGFR mutations, who were randomised to 1st-line afatinib in the LL3/6/7 trials. Data had been prospectively collected as study follow-up information. Tx duration was assessed by descriptive medians or KM estimates. Biopsies at afatinib resistance were not required in LL3/6/7.


Of the 553 pts with common EGFR mutations who received 1st-line afatinib and later discontinued it, 2nd-line therapy was given in 394 (71%) pts and consisted of platinum-based CT for 252 (46%), single agent CT for 39 (7%), 1st-generation EGFR TKI for 49 (9%) and other tx for 54 (10%) pts. Median time on 2nd-line tx was 2.9 months for platinum-based and 1.4 months for single-agent CT, with no relevant difference between Del19 and L858R mutation subgroups. Among 186 (34%) pts who received 1st-generation EGFR TKIs post-afatinib, median time on tx was 3.9 months. Of 212 pts randomised to 1st-line CT in LL3 and LL6, 117 (55%) received 1st-generation EGFR TKI monotherapy as 2nd-line tx, with a median time on tx of 11.2 months. Interestingly, 34 pts received osimertinib after 1st-line afatinib, the majority in ≥ 3rd line; median time on osimertinib tx was 31.5 months (95% CI 16.8–31.5 months). Median OS for osimertinib-treated pts is not yet evaluable.


The majority (71%) of pts who received 1st-line afatinib were fit enough to receive subsequent therapies and there was no relevant difference in 2nd-line tx duration by Del19/L858R EGFR mutation subgroup. Introduction of a different TKI was common, with good outcome. Time on tx with osimertinib after afatinib was unexpectedly long among 34 pts; this should be examined in a larger cohort. Overall, these findings suggest that pts treated with 1st-line afatinib are well suited for subsequent therapies, including CT, 1st-generation EGFR TKIs and osimertinib.

Clinical trial identification

LUX-Lung 3, NCT00949650; LUX-Lung 6, NCT01121393; LUX-Lung 7, NCT01466660

Legal entity responsible for the study

Boehringer Ingelheim


Boehringer Ingelheim


L. Sequist: Advisory boards for Boehringer Ingelheim, AstraZeneca, Novartis, Clovis, Genentech, Merrimack, Ariad, BMS. M. Schuler: Advisory boards for AZ, BI, Celgene, Eli Lilly, Novartis; corporate-sponsored research for BI, BMS, Novartis; honoraria from AZ, BI, BMS, Celgene, Eli Lilly, Novartis, Roche, MSD, Alexion; patents with University Duisburg-Essen. T. Kato: Lecturer fees from AstraZeneca, BI, Chugai, Eli Lilly, MSD, Ono; donations/contributions from BI; research expenses from Taiho, Chugai, AstraZeneca, Eli Lilly, Abbvie, Pfizer, MSD, BMS, BI, Kirin Kyowa, Ono, Merck Serono. H. Tanaka: Advisory board: AstraZeneca; honoraria: Boehringer, Ono pharma, Chugai pharma, Eli Lilly, MSD. T. Hida: Research expenses from Chugai Pharmaceutical, Novartis, Taiho Pharmaceutical, AstraZeneca, Nippon Boehringer Ingelheim, Pfizer, Clovis Oncology, Astellas Pharma. K. Park: Advisory boards for Astellas, AZ, BI, Clovis, Eli Lilly, Hanmi, LOXO, MSD, Novartis, ONO, Roche J. Bennouna: Received honoraria from Roche, Boehringer Ingelheim, Novartis, AstraZeneca and Pierre Fabre and has consulting/advisory roles for Roche, Boehringer Ingelheim, Novartis and Pierre Fabre Medicament. D. Moro Sibilot: Advisory board: Lilly, Roche, BMS, MSD, Novartis, Pfizer, Ariad, AstraZeneca, Boehringer Ingelheim. A.Märten, B. Peil, E. Ehrnrooth: Employee of Boehringer Ingelheim. N. Yamamoto: Ad boards: AZ, BI, Chugai, Eli Lilly, MSD, Novartis, ONO, Taiho Corporate-sponsored research: BI, Chugai, Eli Lilly, MSD Honoraria: AZ, BI, Chugai, Eli Lilly, MSD, Novartis, ONO, Taiho. K. Nakagawa: Advisory board: Astellas Pharma Inc./Eli Lilly Japan K.K./Ono Pharmaceutical Co., Ltd. Corporate-sponsored research: GlaxoSmithKline K.K./AstraZeneca K.K./Kyowa Hakko Kirin Co.,Ltd./Pfizer Japan Inc./AbbVie Inc./Novartis Pharma K.K./Nippon Boehringer Ingelheim Co.,Ltd./Daiichi Sankyo Co., Ltd./Eli Lilly Japan K.K./MSD K.K./Quintiles Inc./Ono Pharmaceutical Co., Ltd./Yakult Honsha Co., Ltd./PAREXEL International Corp/Otsuka Pharmaceutical Co., Ltd./Astellas Pharma Inc./AC MEDICAL INC./Taiho Pharmaceutical Co.,Ltd./Merck Serono Co., Ltd./EPS International Co., Ltd./Covance Inc./Chugai Pharmaceutical Co.,Ltd./Bristol Myers Squibb Company/Eisai Co., Ltd. Honoraria: Astellas Pharma Inc./AstraZeneca K.K./Novartis Pharma K.K./Pfizer Japan Inc./Chugai Pharmaceutical Co.,Ltd./Eli Lilly Japan K.K./MSD K.K./Ono Pharmaceutical Co.,Ltd./Nippon Boehringer Ingelheim Co.,Ltd./Bristol Myers Squibb Company/Kissei Pharmaceutical Co., Ltd./Daiichi Sankyo Co., Ltd./Taiho Pharmaceutical Co.,Ltd./AYUMI Pharmaceutical Corporation. All other authors have declared no conflicts of interest.

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