Results: Median age was 62 years (range: 37-89), 64% females, 86% had a PS 1, 54%/ 13% were never/current smokers. Patients had one (44%), two (34%) or more (22%) prior treatment lines. At diagnosis, patients had EGFR exon 19 deletion (74%), L858R exon 21 mutation (24%) and concomitant exon 18/ exon 20 mutation (2%). Before Osi start, T790M was detected in blood (28%) or tumor tissue (72%). Median follow-up was 15.3 (IQR: 8.6-21.6) months. Overall response rate was 83%, median progression-free survival 15.1 months (IQR: 6.4-20.1), median overall survival 25.1 months (IQR: 16.7-not reached [NR]) and median treatment duration 18.1 months (IQR: 10.1-23.5). At data cut off, PD had occurred in 26 patients (52%). There were 73% oligo- vs. 27% systemic PD. Median treatment duration in patients with oligo-PD was 19.6 vs 6.5 months if systemic PD. The number of progressive lesions in oligo-PD patients were 1 (32%), 2 (37%), 3 (26%), and 5 (5%). Main sites of PD were lung (n¼ 14), bone (n¼ 10), lymph nodes (n ¼ 6), liver and pleura (n ¼ 5 each), and brain (n ¼ 4). 12 patients with oligo-PD continued treatment with Osi beyond progression, ten of them after local therapy (8x radiotherapy, 2x surgery). Median time of treatment beyond PD was 10.7 months in patients with oligo-PD (IQR: 5.7-NR). Analyses of pretreatment and post-PD tumor tissue from a subset of patients will be presented.
Conclusions: In patients with acquired resistance to Osi, we observed a high rate of extrac-ranial oligo-PD. Outcomes of patients with oligo-PD were favorable with the majority con-tinuing Osi in addition to local therapy, supporting the concept of Osi treatment beyond progression in combination with local therapy of progressing lesions.
Legal entity responsible for the study: Kantonsspital St. Gallen. Funding: Institutional funding from AstraZeneca for molecular analysis. Disclosure: S. Schmid: Research funding (Institutional): AstraZeneca, BMS Advisory (Institutional): Boehringer Ingelheim. S.I. Rothschild: Consulting/Advisory Role (Institutional): BMS, AstraZeneca, Lilly, Boehringer Ingelheim, Eisai, Roche, Novartis, Merck Serono, MSD Oncology, Astellas Pharma, Bayer, Pfizer, Takeda; Research funding (institutional): Boehringer Ingelheim, AstraZeneca, BMS, Eisai, Merck Serono; Travel, Accommodation: Roche, Lilly, BMS, AstraZeneca, Merck Sharp and Dohme, Amgen. W-D. Janthur: Advisory boards: Roche, Boehringer Ingelheim, Takeda, MSW-D. M. Fru¨h: Advisory Board AstraZeneca. All other authors have declared no conflicts of interest.
1449P Efficacy of afatinib in the clinical practice: First results of the GIDEON trial: A prospective non-interventional study (NIS) in EGFR mutated NSCLC in Germany W.M. Brueckl1 , E. Laack2 , M. Reck3 , F. Griesinger4 , H. Sch€afer5 , C. Kortsik6 , T. Gaska7 , J. Rawluk8 , S. Kru¨ger9 , K. Kokowski10 , S. Budweiser11 , A. Schueler12 , S. Kiessling12 1
Dept. of Internal Medicine 3, Klinikum Nu¨rnberg, Universit€atsklinik der Paracelsus Medizinischen Privatuniversit€at, Nuremberg, Germany,2
Hemato-Oncology, Hamburg, Germany,3
Airway Research Center North, German Center for Lung Research, LungenClinic Grosshansdorf, Grosshansdorf, Germany,4
Dept. of Hematology and Oncology, Pius Hospital, Oldenburg, Germany,5
Department of Pneumology, SHG-Clinic, Voelklingen, Germany,6
Dept. of Pneumology, KKM St.Hildegardis Krankenhaus, Mainz, Germany,7
Hematology and Oncology, Bruederkrankenhaus St. Josef, Paderborn, Germany,8
Klinik fu¨r Innere Medizin I, Universit€atsklinikum Freiburg Klinik fu¨r Innere Medizin H€amatologie, Onkologie und Stammzelltransplantation, Freiburg, Germany,9
Dept. Pulmonology, Florence-Nightingale-Hospital, Du¨sseldorf, Germany, 10
Dept. of Pneumology, Krankenhaus Mu¨nchen Bogenhausen Med. II Abteilung, Munich, Germany,11
Department of Internal Medicine III, Division of Pulmonary and Respiratory Medicine, RoMed Clinical Centre, Rosenheim, Germany,12
Boehringer Ingelheim Pharma GmbH & Co. KG, Germany, Ingelheim Am Rhein, Germany Background: Afatinib is an irreversible ErbB family blocker, which is approved as monotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. Here we report the first interim analysis of the NIS GIDEON, which was initiated to investigate the efficacy and tolerability of Afatinib in first line treatment in the daily clinical routine in Germany.
Methods: EGFR-mutated NSCLC patients were treated with Afatinib according to label until progression, death or discontinuation due to patients’ or physicians’ decision. Efficacy (objective response rate, ORR; disease control rate, DCR and progression-free survival, PFS) was prospectively assessed by investigators and additional data about tol-erability under everyday treatment conditions were documented.
Results: A total of 151 pat. were enrolled in the study and received Afatinib treatment. EGFR mutations comprised exon 19 deletions (Del19, 56.6 %), L858R point mutations (21.9 %) and uncommon mutations (18.5 %). Median age was 67 years (38-89) with 91 Pat.65 years (60.3%). Pat. started treatment on 40mg/d (72.8 %) Afatinib or < 40mg/d (25.8 %). Dose reductions during the course of therapy were frequent, 61.8 % with 40mg/d starting dose and 53.8% with <40mg/d. ORR for the total treated population was 73% with a DCR of 90 %. ORR was similar according to different subgroups, e.g. mutation type and age. mPFS at the time of analysis was 12.9 Mon. and in the group of pat.65 years 13.7 Mon. OS date are not mature yet. The most frequent documented AEs were diarrhea and rash/acne, with 11.6 % of pat. discontinued treatment due to drug related AEs. Conclusions: Afatinib is a standard therapy for patients with activating EGFR muta-tions in Germany. The first results of this prospective NIS confirm the robust clinical data for Afatinib in the clinical routine setting, especially in the elderly population, which is underrepresented in clinical trials. A starting dose of < 40 mg Afatinib in selected pat. does not seem to be inferior in terms of efficacy.
Clinical trial identification: NCT02047903.
Legal entity responsible for the study: Boehringer Ingelheim Pharma GmbH & Co. KG, Germany.
Funding: Boehringer Ingelheim Pharma GmbH & Co. KG, Germany.
Disclosure: W.M. Brueckl: Payments for membership on advisory boards: Boehringer Ingelheim. M. Reck: Honoraria for lectures and consultancy: Hoffmann-La Roche, Lilly, Boehringer Ingelheim, Abbot, AstraZeneca, Celgene, BMS, MSD, Merck, Novartis and Pfizer. S. Kru¨ger: Honoraria, Advisory boards and lectures: Boehringer Ingelheim. A. Schueler, S. Kiessling: Employee: Boehringer Ingelheim Pharma GmbH & Co. KG. All other authors have declared no conflicts of interest.
1450P Osimertinib treatment for patients with EGFR exon 20 insertion positive non-small cell lung cancer
B. van Veggel1
, A. van der Wekken2
, S. Hashemi3 , R. Cornelissen4 , K. Monkhorst5 , D. Heideman6 , T. Radonic6 , E.F. Smit7 , E. Schuuring8 , J. De Langen1 1
Thoracic Oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL), Amsterdam, Netherlands,2
Pulmonary Diseases, University of Groningen, Groningen, Netherlands,3
Pulmonary Diseases, VU University Medical Center, Amsterdam, Netherlands, 4
Pulmonary Diseases, Erasmus MC, Rotterdam, Netherlands,5
Pathology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, Netherlands, 6
Pathology, VU University Medical Center, Amsterdam, Netherlands,7
Pulmonary Diseases, The Netherlands Cancer Institute, Amsterdam, Netherlands,8
Pathology, University Hospital Groningen (UMCG), Groningen, Netherlands
Background:Epidermal growth factor receptor (EGFR) exon 20 insertions are identi-fied in 4-10% of al EGFR mutations in non-small cell lung cancer (NSCLC) and are generally associated with primary resistance to first and second generation EGFR tyro-sine kinase inhibitors (TKIs). In vitro and preclinical animal studies have shown that osimertinib exerts antitumor activity in EGFR exon 20 insertion positive NSCLC cell lines. We report on a cohort of advanced stage NSCLC patients, harboring an EGFR exon 20 insertion, that was treated with osimertinib.
Methods:17 patients with advanced NSCLC harboring an EGFR exon 20 insertion were treated with osimertinib 80 mg once daily, in four institutions in the Netherlands. Data were obtained retrospectively. EGFR mutation status was assessed by next-genera-tion sequencing. Progression free survival (PFS), disease control rate (DCR) and objec-tive response rate (ORR) were assessed using RECIST v1.1.
Results:Median age was 63 years (range 35 – 81), 71% was female and median number of prior systemic treatments was 1 (range 0 – 3). Ten patients (59%) received prior plat-inum-based chemotherapy, and 2 patients afatinib, one patient experienced stable dis-ease for 11 months, the other patient showed progression. Among all patients treated with osimertinib, we observed 1 partial response, 13 patients with stable diseases and 3 with progressive disease as best response (ORR 6%). Two patients were still on osimer-tinib treatment at the cut-off date. Median PFS was 3.7 months (95% CI: 2.3 – 5.4 months). Six of seventeen patients (35%) achieved DCR at five months.
Table: 1450P Patient Number of prior treatments Prior platinum based chemotherapy Prior EGFR TKI Best RECIST response PFS (months) 1 2 Yes no SD 4.0 2 1 Yes no SD 1.6 3 2 Yes no PR 0.7 4 1 Yes no PR 0.7 5 2 Yes no SD 3.8 6 1 Yes no SD 3.0 7 3 Yes no SD 9.3 8 1 Yes no SD 17.0 9 1 No no SD 3.7 10 1 Yes no SD 17.2 11 0 No no PR 3.1 12 0 No no SD 2.6 13 0 No no SD 6.5 14 3 Yes afatinib (SD) SD 7.9 15 1 No afatinib (PD) PD 1.7 16 0 no no SD 8.3 17 0 no no SD 1.4
EGFR, epidermal growth factor receptor; RECIST: Response Evaluation Criteria in Solid Tumors; PR, partial response; SD, stable disease; PD, pro-gressive disease; PFS, progression free survival
abstracts
Annals of Oncology
viii524 | NSCLC, metastatic
Volume 29 | Supplement 8 | October 2018
Conclusions:Osimertinib has limited antitumor activity in patients with EGFR exon 20 mutated NSCLC, with an ORR of 6%. A subset of patients (35%) seems to derive benefit from osimertinib treatment with durable disease control for more than five months.
Legal entity responsible for the study:J. de Langen. Funding:Has not received any funding.
Disclosure:All authors have declared no conflicts of interest.
1451P The characteristics and clinical outcome of metastatic NSCLC harboring uncommon EGFR mutation at Thailand’s tertiary referral center J. Chantharasamee1 , N. Poungvarin2 , P. Danchaivijitr1 , S. Techawatanawanna1 1
Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand,2
Clinical Pathology, Siriraj Hospital, Mahidol University, Bangkok, Thailand
Background: An uncommon EGFR-mutant NSCLC is a rare subset of NSCLC. Prevalence and clinical outcome of this entity remain unclear. Several studies have reported the benefit of EGFR-tyrosine kinase inhibitor in patients harboring complex or uncommon EGFR mutations but there are insufficient data to determine the advant-age of EGFR-TKI over chemotherapy. This study aimed to review the prevalence and clinical outcome of treatment of uncommon EGFR-mutant patients in real-world practice.
Methods: We retrospectively reviewed medical records of 681 patients tested for EGFR mutation NSCLC during 2014-2018 to collect the mutational status and to compare the survival outcomes between the patients treated with EGFR-TKI and chemotherapy. Results: At a median follow-up of 19.1 months, 317 (47%) patients were identified with EGFR-mutant NSCLC. Twenty-eight patients (8.8%) harbored uncommon EGFR mutations. Of those 28 patients, the most frequent single mutation was exon20 inser-tion (21%, n¼ 6); 5 were L861Q and 4 were G719X. 13 (46%) patients had compound mutations: 4 were G719X plus S768I; 4 were de novo T790M plus either L858R or dele-tion(del)19; 2 were L858R plus del19; 1 was L858R plus Ex20Ins; 1 was del19 plus KRAS mutation, and 1 with G719X plus E709A was found in squamous cell carcinoma. History of tobacco use was found in 50% of patients. 100% of male patients with G719X mutation were smokers. 57% of the 28 patients were treated with EGFR-TKI, mostly 1stgeneration, and 29% were treated with chemotherapy alone. The objective response rate was 56% in the TKI group. Median progression-free survival (PFS) in the TKI group was 10.2 months. 5-year overall survival (OS) rate was 34%. Patients treated with TKI had significantly better 5-year OS rate than those who had never received TKI (54% vs. 17%, 95%CI 1.23-14.66, p log-rank¼ 0.02). The longest OS was 73.6 months in a patient with del19 plus de novo T790M.
Conclusions: This study demonstrated the benefit of 1stgeneration EGFR-TKI was greater than with chemotherapy alone in the patients with uncommon or compound EGFR mutation NSCLC. Rare EGFR mutations can be detected in squamous cell carci-noma. There was a high prevalence of smoking among the male patients with G719X-mutant NSCLC.
Legal entity responsible for the study: Jomjit Chantharasamee. Funding: Has not received any funding.
Disclosure: All authors have declared no conflicts of interest.
1452P Combination of the S49076 with gefitinib in NSCLC patients progressing on EGFR-TKI and harboring MET/AXL dysregulation S. Viteri1 , G-C. Chang2 , R. Chiari3 , B.C. Cho4 , F. Ciardiello5 , G. Curigliano6 , T. Hida7 , D.H. Lee8 , W.T.D. Lim9 , C-C. Lin10 , A. Martinez11 , H. Murakami12 , I. Natsume13 , M. Nishio14 , L. Paz-Ares15 , R.A. Soo16 , V. Cattan17 , E. Gandossi18 , H. Heck19 , K. Park20 1
Servicio Oncologıa Me´dica, Instituto Universitario USP Dexeus, Barcelona, Spain, 2
Oncology, Taichung Veterans General Hospital, Taichung, Taiwan,3
S.C. Oncologia Medica, Azienda Ospedaliera di Perugia S. Maria della Misericordia, Perugia, Italy, 4
Medical Oncology, Yonsei Cancer Center Yonsei University, Seoul, Republic of Korea, 5
Dipartimento Medico di Internistica Clinica e Sperimentale, Universita degli Studi della Campania Luigi Vanvitelli, Naples, Italy,6
Early Drug Development for Innovative Therapies Division, Istituto Europeo di Oncologia, Milan, Italy,7
Department of Thoracic Oncology, Department of Thoracic Oncology, Aichi, Japan,8
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea9
Clinical Trial and Epidemiological Sciences, National Cancer Centre Singapore, Singapore,10
Department of Oncology, National Taiwan University Hospital, Taipei City, Taiwan,11
Servicio Oncologıa Me´dica, Vall d’Hebron University Hospital, Barcelona, Spain,12
Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan, 13
Department of Oncology, Yokosuka Kyosai Hospital, Yokosuka Kyosai, Japan, 14
Thoracic Oncology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan,15
Medical Oncology, University Hospital 12 de Octubre, Madrid, Spain,16
Haematology-Oncology, National University Hospital, Singapore, 17
Translational Research, Servier France, Suresnes, France,18
Servier Oncology, Servier France, Suresnes, France,19
Dpt of Pharmacokinetics, Servier, Suresnes, France,20 Div. of Heamatology/Oncology, Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
Background: EGFR T790M mutation is the most common acquired mechanism of resistance in NSCLC patients treated with EGFR-TKI. Alternative mechanisms include activation of the receptor tyrosine kinases MET or AXL. S49076 is a multi-target inhibi-tor and a potent ATP-competitive TKI that targets MET, AXL and FGFR1/2/3. Here we report phase 1 molecular and safety data of resistant patients without the EGFR T790M mutation that were treated with S49076 combined with gefitinib.
Methods: A dose-escalation of S49076 in combination with gefitinib 250 mg once daily was conducted using a modified Bayesian Continual Reassessment Method. Toxicity was evaluated according to Common Terminology Criteria for Adverse Events (AEs), v4.0. Resistant patients were selected according to a tumor molecular profile including presence of the activating EGFR mutation, absence of T790M and with at least one of the following: MET amplification, or MET or AXL overexpression.
Results: The molecular profile screening has been performed in 46 EGFR/T790M-neg-ative tumour samples. In total, 23/46 met the molecular eligibility criteria: 21 with MET dysregulation (11 MET amplification, 20 MET overexpression and 4 both MET / AXL dysregulations), and 2 with AXL overexpression only. Fourteen patients were treated: 4 received the 500 mg dose and 10 received the 600 mg dose, which was consid-ered as the recommended dose. Related AEs included diarrhoea, paronychia, asthenia, nausea, vomiting, ALAT and ASAT increase, anaemia, peripheral oedema and yellow skin, mostly grade 1-2. One patient experienced a DLT at 600 mg (grade 3 stomatitis); 2 patients experienced 3 serious related AEs (asthenia, atrial fibrillation and diarrhoea). No grade 4-5 AEs were reported. Concomitant intake of gefitinib did not appear to modify the S49076 PK profile as compared to previous data. Limited anti-tumour activity was observed in the 12 evaluable patients: 1 partial response and 9 stable diseases.
Conclusions: S49076 combined with gefitinib is well tolerated and data are consistent with the overall safety profile of each drug. The observed frequency of MET dysregula-tion was comparable to those reported in the literature whereas AXL overexpression was lower than expected.
Clinical trial identification: EudraCT: 2015-00264631. Legal entity responsible for the study: Servier group. Funding: Servier group.
Disclosure: S. Viteri: BMS: Speaker bureau/ Consultant: Roche G.-C. Chang: Honoraria: Hoffman-La-Roche, Merck Sharp & Dohme, BMS, BI, Pfizer, AstraZeneca, Eli Lilly, Compagny Oncology. G. Curigliano: Speaker: Roche, Pfizer, Novartis. T. Hida: Research funding: Novartis, Pfizer, AstraZeneca. D.H. Lee: Honoraria: AstraZeneca, BMS, Ono Pharm, Merck, Lilly, BI, Pfizer, Novartis, CT Cube, Takeda, Roche, Samyang Biopharma, BMS, Janses, MSD, Mundipharma, CJ Healthcare. H. Murakami: Honoraria, Speaker, Grants and Research: AstraZeneca, BMS, Ono Pharm, Merck, Lilly, Chugai Pharm, BI, Pfizer, Taiho, Novartis. M. Nishio: Speaker fees as Honoraria, Consultant, Research funding: Ono Pharmaceutical, Bristol Myers Squibb, Pfizer, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, Boehringer ingelheim, MSD, Novartis, Daiichi Sankyo Healthcare, Merck Serono, Astellas. L. Paz-Ares: Honoraria: Roche, Lilly, MSD, BMS, Novartis, Pfizer, Boehringer Ingelheim, AstraZeneca, Merck Serono, Amgem, Clovis Oncology. R.A. Soo: Honoraria, Advisory board, Research: AstraZeneca, BMS, Merck, Lilly, Roche, BI, Pfizer, Taiho, Novartis. V. Cattan, E. Gandossi, H. Heck: Employee: Servier. K. Park: Advisor/consultant: Astellas, AstraZeneca, BI, BMS, Clovis, Daiichi Sankyo, EliLilly, GSK, Hanmi, KHK, MSD, Novartis, Roche Research fund; AstraZeneca. All other authors have declared no conflicts of interest.
