Closing remarks (ID 51)
Event: ELCC 2017
Type: Closing remarks
Moderators:M. Reck, A.G. Nicholson
Coordinates: 5/08/2017, 12:50 - 13:00, Room A
Closing remarks (ID 576)
12:50 - 13:00 | Author(s): A.G. Nicholson
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ESMO recommendations (ID 32)
Type: Educational session
Moderators:S. Novello, M. Frueh
NSCLC (ID 128)
11:20 - 12:50 | Author(s): S. Novello
SCLC (ID 129)
11:20 - 12:50 | Author(s): M. Frueh
Mesothelioma (ID 130)
11:20 - 12:50 | Author(s): P. Baas
Thymic (ID 131)
11:20 - 12:50 | Author(s): N. Girard
Moderators:M. Perol, L. Paz-Ares
Save the date (ID 708)
12:50 - 13:00 | Presenting Author(s): M. Perol, L. Paz-Ares
Combined treatment stage III (ID 3)
Moderators:S. Peters, M. Guckenberger
When concurrent chemo-radiotherapy is not the preferred choice (ID 7)
14:30 - 16:00 | Presenting Author(s): P. Fournel
Are current NTCP models useful for predicting radiation-induced toxicity? (ID 8)
14:30 - 16:00 | Presenting Author(s): D. De Ruysscher
Surgical salvage of recurrences following CT-RT: Indications and outcomes (ID 9)
14:30 - 16:00 | Presenting Author(s): C. Dickhoff
Immunotherapy in the stage III paradigm: Rationale and clinical data (ID 10)
14:30 - 16:00 | Presenting Author(s): S. Peters
Combining radiation with non-chemotherapy agents (ID 19)
Type: Multidisciplinary Interactive Session (MIS)
Moderators:N. Andratschke, A. Naing
Combining radiotherapy with TKIs in oligo-progressive oncogene addicted NSCLC (ID 78)
08:00 - 08:50 | Presenting Author(s): N. Andratschke
Combining radiotherapy with immune-checkpoint inhibitors (ID 79)
08:00 - 08:50 | Presenting Author(s): A. Naing
Developments in pharmacology for systemic therapy (ID 11)
Type: Specialty session
Moderators:D. Carbone, J. Mazieres
Pharmacokinetics and interaction for TKI treatment (ID 43)
11:00 - 12:30 | Presenting Author(s): S. Popat
Dosing and scheduling of monoclonal antibodies (ID 44)
11:00 - 12:30 | Presenting Author(s): T. Yap
Target treatment combinations: Rationale and evidence (ID 45)
11:00 - 12:30 | Presenting Author(s): D. Carbone
Interactions of immunotherapy with other therapies (ID 46)
11:00 - 12:30 | Presenting Author(s): S. Champiat
Early stage NSCLC: Where do we stand in 2018? (ID 5)
Moderators:S. Siva, K. Suzuki
Guidelines for surgery in ground glass opacities (ID 17)
16:30 - 18:00 | Presenting Author(s): K. Suzuki
Pathology and biomarkers in resected NSCLC (ID 18)
16:30 - 18:00 | Presenting Author(s): E. Brambilla
Neoadjuvant immunotherapy in early-stage NSCLC (ID 19)
16:30 - 18:00 | Presenting Author(s): P. Forde
Stereotactic radiotherapy for early stage NSCLC (ID 20)
16:30 - 18:00 | Presenting Author(s): S. Siva
Guiding the best targeted treatment (ID 27)
Type: Multidisciplinary Tumour Board
Moderators:E. Smit, F. Lopez-Rios
Can we rely on liquid biopsy for treatment decision at the time of acquired resistance? (ID 109)
14:45 - 16:15 | Presenting Author(s): J. Remon-Masip
EGFR activating mutation plus exon 20 co-mutation at baseline: Which TKI should we select for frontline treatment? (ID 110)
14:45 - 16:15 | Presenting Author(s): E. Smit
Progression on osimertinib: When is it possible to continue with a targeted therapy? (ID 111)
14:45 - 16:15 | Presenting Author(s): D. Planchard
How can we optimise our organisation to deliver precision oncology? (ID 18)
Moderators:P. Garrido Lopez, F. Barlesi
Organisational models for biomarkers testing (ID 73)
Access to personalised medicine (ID 74)
16:45 - 18:15 | Presenting Author(s): P. Garrido Lopez
The pathologist's point of view (ID 75)
16:45 - 18:15 | Presenting Author(s): F. Lopez-Rios
The patient's point of view (ID 76)
16:45 - 18:15 | Presenting Author(s): S. Novello
Immunotherapy and next-generation TKIs: From second to frontline treatment (ID 55)
Type: Poster Discussion session
Presentations: 14
Moderators:P. Garrido Lopez, S. Ekman, S. Ortiz-Cuaran, E. Wauters
134PD - Primary PFS and safety analyses of a randomized phase III study of carboplatin + paclitaxel +/− bevacizumab, with or without atezolizumab in 1L non-squamous metastatic NSCLC (IMpower150) (ID 469)
07:45 - 09:00 | Presenting Author(s): M. Reck | Author(s): M.A. Socinski, F. Cappuzzo, F. Orlandi, D. Stroyakovskiy, N. Nogami, D. Rodríguez-Abreu, D. Moro-Sibilot, C.A. Thomas, F. Barlesi, G. Finley, C. Kelsch, A. Lee, S. Coleman, Y. Shen, M. Kowanetz, A. Lopez Chavez, A. Sandler, R.M. Jotte
Atezolizumab (atezo; anti–PD-L1) inhibits PD-L1 binding to PD-1 and B7.1, restoring anti-cancer immunity. Bevacizumab (bev) may further enhance atezo efficacy by inhibiting VEGF immunosuppression and promoting T-cell tumour infiltration. IMpower150 evaluates the addition of atezo to carboplatin (C) + paclitaxel (P) ± bev in chemo-naive patients (pts) with non-squamous (NSQ) mNSCLC.
1202 pts received atezo 1200 mg + C AUC 6 + P 200 mg/m[2] (Arm A) or atezo + bev 15 mg/kg + C + P (Arm B) vs bev + C + P (Arm C) IV q3w for 4 or 6 cycles per investigator (INV) discretion, then maintenance atezo, atezo + bev or bev, respectively. Co-primary endpoints assessed at this data cutoff (15 Sep 2017; minimum follow up, 9.5 mo) were INV-assessed PFS in the ITT-WT (EGFR or ALK negative) population and in WT pts with expression of a tumour T-effector gene signature (Teff-WT; centrally assessed), and OS in the ITT-WT population, for the Arm B vs Arm C comparison. Due to pre-specified statistical testing hierarchy, Arm A vs Arm C has not been formally tested yet.
356 pts in Arm B and 336 pts in Arm C were enrolled in the ITT-WT. Median age was 63 y; 60% were previous smokers (both arms). 61% and 62% were male, and 39% and 43% had ECOG PS 0 in Arms B and C, respectively. The HRs for INV-assessed PFS in Arm B vs C were 0.62 (95% CI: 0.52, 0.74; P < 0.0001) in the ITT-WT and 0.51 (0.38, 0.68; P < 0.0001) in the Teff-WT populations. Median PFS in Arm B vs C was 8.3 mo vs 6.8 mo and 11.3 mo vs 6.8 mo in the ITT-WT and Teff-WT populations, respectively. PFS benefit was seen regardless of PD-L1 IHC status, including PD-L1–negative pts (TC0/IC0; HR, 0.77 [95% CI: 0.61, 0.99]). Landmark PFS and ORR are shown (Table). Arm B had a comparable safety profile to Arm C; treatment-related serious AEs were 25% vs 19%, respectively.Table:IMpower150 Primary PFS Analysis, Landmark PFS and ORR
Arm C (bev + C + P; N = 400)
Arm B (atezo + bev + C + P; N = 400)
ITT-WT population[a] n = 336 n = 356
Median PFS (95% CI), mo 6.8 (6.0, 7.1) 8.3 (7.7, 9.8)
HR (95% CI; P value) 0.62 (0.52, 0.74; P < 0.0001)
ITT-WT landmark PFS (95% CI), %
6-month 56% (51, 62) 67% (62, 72)
12-month 18% (13, 23) 37% (31, 42)
ORR[b,c] (95% CI), % 48% (43, 54) 64% (58, 68)
Teff-WT population[a] n = 129 n = 155
Median PFS (95% CI), mo 6.8 (5.9, 7.4) 11.3 (9.1, 13.0)
Teff-WT landmark PFS (95% CI), %
ORR[b,d] (95% CI), % 54% (44, 62) 69% (61, 76)
HR, hazard ratio; ORR, objective response rate; PFS, progression-free survival; Teff, T-effector; WT, wild-type.aWT populations exclude patients with EGFR or ALK driver mutations.bUnconfirmed ORR.cn = 353 in Arm B and n = 331 in Arm C.dn = 153 in Arm B and n = 127 in Arm C.
IMpower150 is the first Phase III study to show a statistically significant and clinically meaningful PFS benefit with atezo + bev + chemo vs bev + chemo in pts with 1L NSQ mNSCLC. Acknowledgement of contribution: G. Finley (Allegheny Cancer Center, Pittsburgh, PA, USA), R. Jotte (Rocky Mountain Cancer Centers, Denver, CO, USA), C. Kelsch, A. Lee, S. Coleman, Y. Shen, M. Kowanetz, A. Lopez-Chavez, A. Sandler (Genentech, Inc., South San Francisco, CA, USA).
Clinical trial identification:
Legal entity responsible for the study:
F. Hoffmann-La Roche Ltd/Genentech, Inc
M. Reck: Consulting or Advisory Role: Lilly, F.Hoffmann‐La Roche, BI, BMS, MSD, AstraZeneca, Merck, Novartis, Pfizer, Celgene. Speakers' Bureau: F. Hoffmann‐La Roche, Lilly, Pfizer, BI, AstraZeneca, MSD, BMS, Merck, Novartis, Pfizer, Celgene. M. A. Socinski: Honoraria: Genentech, Speakers Bureau: Genentech, Research Funding: Genentech. F. Cappuzzo: Participation in advisory boards for Roche, AZ, BMS, Takeda, MSD, Lilly, Pfizer. F. Orlandi: Research grants from Astrazeneca, MSD, Genetech-Roche, Advisory tasks for AstraZeneca, Roche, Boehringer Ingelheim, Pfizer. N. Nogami: Honoraria: Meiji Seika Pharma Co., Ltd., AstraZeneca, Pfizer Inc., Bristol‐Myers Squibb, ONO Pharmaceutical CO., LTD., Kyowa Hakko Kirin, Taiho Phamaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd, Eli Lilly Japan, Boehringer Ingelheim. D. Rodríguez-Abreu: Honoraria for lectures and Advisory Board from Bristol-Myers-Squibb, Merck Sharp & Dohme and Hoffmann-La Roche. D. Moro-Sibilot: Advisory boards for Roche, MSD, Pfizer, Novartis, BMS, Astra Zeneca, Lilly. F. Barlesi: Honarium from Genentech & Roche. G. Finley: Promotional speaking on behalf of Bristol Meyers, Boehringer Ingleheim, and Astellas Medivation, and Merck. C. Kelsch: Genentech Employee with Roche Stock. A. Lee: Genentech Employee with Roche Stock. S. Coleman: Genentech Employee with Roche Stock. Y. Shen: Genentech Employee with Roche Stock. M. Kowanetz: Genentech Employee with Roche Stock. A. Lopez-Chavez: Genentech Employee with Roche Stock. A. Sandler: Genentech Employee with Roche Stock. All other authors have declared no conflicts of interest.
136PD_PR - 3-year survival and duration of response in randomized phase II study of atezolizumab (atezo) vs docetaxel (doc) in 2L+ NSCLC (POPLAR) (ID 607)
07:45 - 09:00 | Presenting Author(s): J. Mazieres | Author(s): K. Park, C. Lewanski, S. Gadgeel, L. Fehrenbacher, A. Rittmeyer, J. Han, A. Artal-Cortes, F. Braiteh, M. Gandhi, W. Yu, C. Matheny, P. He, A. Sandler, M. Ballinger, J. Vansteenkiste
Atezo (anti–PD-L1) has demonstrated OS benefit over doc in a randomized Phase II study, POPLAR, in patients with advanced NSCLC. This benefit has been confirmed in the randomized Phase III study OAK (Rittmeyer, 2017). The 3-year survival analysis of the POPLAR study presented here describes the longest survival follow-up reported to date of an all-comer randomized PD-L1/PD-1 immunotherapy trial in 2L + NSCLC.
Patients were randomized 1:1 to receive atezo (1200 mg) or doc (75 mg/m[2]) IV q3w. Tumors were prospectively evaluated for tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression using the VENTANA SP142 IHC assay. Landmark OS was estimated using the Kaplan-Meier method. Data cutoff, April 7, 2017; minimum follow-up, 3 years.
The 2-year and 3-year survival with atezo vs doc were 32.2% vs 16.6% and 18.7% vs 10.0%, respectively. The long-term OS benefit of atezo vs doc was observed across histology and PD-L1 expression subgroups (Table). While the TC3 or IC3 subgroup derived the greatest OS benefit, the TC0 and IC0 subgroup also had improved long-term OS with atezo vs doc. The ITT ORR was 15% in both atezo and doc arms, but the median duration of response was 3 times longer with atezo (22.3 months [95% CI: 11.6, 31.1] vs 7.2 months [95% CI: 5.8, 12.2] with doc). Seven of the 11 doc-arm 3-year survivors received subsequent non-protocol therapy with anti–PD-L1/PD-1 agents. Atezo had a favorable safety profile compared with doc that was consistent with previous reports.Table:Landmark OS in the ITT, PD-L1 expression, and histology subgroups in POPLAR
Population (n, atezo vs doc)
2-year OS rate, %
Atezo
P value[a]
ITT (144 vs 143) 32.2% 16.6% 0.0027 18.7% 10.0% 0.0419
PD-L1 Expression Subgroups
TC3 or IC3 (24 vs 23) 41.7% 19.9% 0.1003 37.5% 14.9% 0.0724
TC2/3 or IC2/3 (50 vs 55) 36.1% 13.8% 0.0082 21.2% 9.9% 0.1166
TC1/2/3 or IC1/2/3 (93 vs 102) 36.0% 19.8% 0.0124 18.0% 11.0% 0.1759
TC0 and IC0 (51 vs 41) 25.0% 6.8% 0.0202 20.5% 6.8% 0.0693
Histology Subgroups
Non-squamous (95 vs 95) 32.2% 21.1% 0.0960 23.3% 12.4% 0.0585
Squamous (49 vs 48) 32.7% 7.8% 0.0020 9.4% 5.2% 0.4603
aFor descriptive purpose only. TC3 or IC3 = PD-L1 ≥ 50% TC or 10% IC; TC2/3 or IC2/3 = PD-L1 ≥ 5% TC or IC; TC1/2/3 or IC1/2/3 = PD-L1 ≥ 1% TC or IC; TC0 and IC0 = PD-L1 < 1% TC and IC. NCT01903993.
Atezo demonstrates superior 2-year and 3-year OS benefit compared with doc, and this benefit is observed across histology and PD-L1 expression subgroups (including TC0 and IC0). Atezo is well tolerated, and responses are highly durable. These results are consistent with long-term OS results from OAK (Satouchi, WCLC 2017). Acknowledgement of contribution: M. Gandhi, W. Yu, C. Matheny, P. He, A. Sandler, M. Ballinger, Genentech, Inc., South San Francisco, CA, USA.
F. Hoffmann-La Roche Ltd/Genentech, Inc.
K. Park: Consulting/Advisory Role: Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Lilly, Hanmi, Kyowa Hakko Kirin, Novartis, Ono Pharmaceutical, Roche. Speakers Bureau: Boehringer Ingelheim, Research Funding: AstraZeneca. C. Lewanski: Consultant: MSD, Roche, AstraZeneca. S. Gadgeel: Speaker's bureau- Astra-Zeneca, Genentech/Roche Advisory Boards: Astra-Zeneca, Ariad, Pfizer, Bristol Myers Squibb and Genentech/Roche. A. Rittmeyer: Grants as an advisor or speaker by: Astra Zeneca, BMS, Boehringer Ingelheim, Eli Lilly, Pfizer and Roche Genentech. A. Artal-Cortes: Advisory boards: Roche, BMS, MSD Travel fees: Roche. F. Braiteh: Speaking and consulting fees received From Genentech. M. Gandhi: Genentech employee and Roche stock. W. Yu: Genentech employee and Roche stock. C. Matheny: Genentech employee and Roche stock, Roche/Genentech travel, accommodations, expenses patents, royalties or other intellectual property: Stanford University (patient with Stanford, do not currently receive royalties or have other intellectual property). P. He: Genentech employee and Roche stock. A. Sandler: Genentech employee; Roche and Amgen stock, Husband has stocks for Allergan and Gilead. M. Ballinger: Genentech employee and Roche stock. All other authors have declared no conflicts of interest.
137PD - Prognostic factors in oligometastatic non-small-cell lung cancer (OM-NSCLC) (ID 616)
07:45 - 09:00 | Presenting Author(s): O. Juan | Author(s): J.A. Méndez, B. Domingo-Arrué, D. Lorente Estelles, C. Escoín, C. Salvador Coloma, E. Navarro, M. Melian Sosa, N. Mancheño, J. Gomez Codina
OM-NSCLC represents a distinct prognostic group within stage IV lung cancer. An increase in overall survival (OS) has been suggested with ablative (surgery or radiotherapy) therapy. We performed an analysis of clinical factors influencing outcome in a series of patients (pts) with OM-NSCLC treated in a tertiary hospital.
OM-NSCLC pts (defined as ≤3 metastatic lesions at diagnosis) diagnosed between Jan-2012 and Dec-2016 were included in the analysis. Median OS was calculated with the Kaplan-Meier method. The association between clinical and pathological factors and OS was determined using uni- (UV) and multivariable (MV) Cox regression models. Variables with a p-value <0.01 in UV analysis were included in the MV model.
84 pts were identified: 25 pts squamous histology (29.8%), 58 adenocarcinoma (58%) and 1 (1.2%) undifferentiated carcinoma. 11 pts (13%) were EGFR-mutation positive. Most patients presented with one (78.3%) or two (20.5%) metastatic sites: CNS (39.2%), bone (29.8%), lung (17.9%), adrenal (11.9%) and liver (10.7%). 57 pts (67.9%) underwent local treatment (8.8% surgery, 70.2% radiotherapy, both 21.2%) before (68.2%) or during (49.1%) chemotherapy. Median follow-up was 10.5 months with a median OS of 15.8 months (95CI%:8.9–22.7). In MV OS analysis, only T-stage (p = 0.012) and histology (p = 0.006) were significantly associated with OS (Table).Table:UV and MV Cox-regression Models
Univariate
HR (CI95%)
p-valor
Histology 0,32 (0.18–0.58) <0.001* 0.42 (0.23–0.78) 0.006
Sex 0,44 (0.19–1.03) 0.059* 0.52 (0.22–1.25) 0.142
Smoking 1,27 (0.79–2.05) 0.320
T stage 1,47 (1.16–1.89) 0.002* 1.44 (1.09–1.92) 0.012
N stage 1,01 (0.99–1.02) 0.496
N° of metastasis 1,32 (0.72–2.41) 0.366
Site of metastasis
Lung 0.80 (0.41–1.58) 0.522
Adrenal gland 0.91 (0.49–1.69) 0.767
CNS 0.89 (0.55–1.45) 0.647
Liver 1.36 (0.76–2.44) 0.302
Bone 1.45 (0.91–2.33) 0.118
Other 1.05 (0.42–2.63) 0.916
Local treatment (yes/no) 0.42 (0.24–0.76) 0.004* 0.61 (0.33–1.12) 0.115
Ablative therapy in OM-NSCLC pts was not associated with higher OS. Only a lower initial T-stage in the primary tumor and adenocarcinoma histology could represent a favorable prognosis. The optimal management of NSC-OM patients will require robust data from well-designed prospective clinical trials.
Medical Oncology, Hospital La Fe.
Has not received any funding
All authors have declared no conflicts of interest.
Invited Discussant 134PD, 136PD and 137PD (ID 674)
138PD_PR - Patient-reported outcomes (PROs) in ALEX: A phase III study of alectinib (ALEC) vs crizotinib (CRIZ) in non-small-cell lung cancer (NSCLC) (ID 464)
07:45 - 09:00 | Presenting Author(s): M. Perol | Author(s): S. Peters, N. Pavlakis, E. Levchenko, M. Platania, J. Oliveira, S. Novello, T. Karagiannis, A. Zeaiter, R. Dziadziuszko
ALEC showed superior efficacy versus CRIZ in patients (pts) with treatment-naïve ALK+ NSCLC in the phase III ALEX trial (NCT02075840). PRO data (disease burden, symptom tolerability and health-related quality of life [HRQoL]) are reported here.
Pts (n = 303) were randomised 1:1 to receive ALEC (600 mg BID) or CRIZ (250 mg BID). Primary endpoint: investigator-assessed PFS. PROs were collected using EORTC QLQ-C30/QLQ-LC13 questionnaires. Pre-specified endpoints: time-to-deterioration (TTD) in lung cancer symptoms and HRQoL, longitudinal analyses of mean score changes from baseline, and proportion of pts with clinically meaningful change (≥10-point change from baseline) during treatment in the ITT population and patients with baseline CNS metastases.
Baseline completion rates and characteristics were balanced between arms in the PRO-evaluable population (ALEC n = 100, 65.8%; CRIZ n = 97, 64.2%). Median TTD in composite symptom endpoint (cough, dyspnoea, chest pain) was similar between arms (HR 1.10 [95% CI 0.72–1.68]). On average, ALEC pts reported a clinically meaningful improvement in baseline lung cancer symptoms for a longer duration of time versus CRIZ (cough, week 96 vs week 84; chest pain, week 96 vs week 80; fatigue, week 96 vs 68; pain in other parts, week 96 vs 68, respectively). Differences in lung symptoms between treatment arms tended to favour ALEC from 11.1 months (45 weeks), which was around the time of median PFS with CRIZ. ALEC pts reported a clinically meaningful improvement from baseline in HRQoL for a longer duration of time than CRIZ pts (week 88 vs 68, respectively). Fewer ALEC pts experienced a clinically meaningful worsening in treatment-related symptoms (nausea/vomiting, diarrhoea, appetite loss, dysphagia, peripheral neuropathy) than CRIZ pts.
TTD for lung cancer symptoms was comparable between arms. Clinically meaningful improvement in lung cancer symptoms was maintained for longer with ALEC versus CRIZ, consistent with the improved PFS with ALEC versus CRIZ. HRQoL was improved with ALEC versus CRIZ. PRO data are consistent with ALEX safety data and confirm greater tolerability with ALEC versus CRIZ.
BO28984; 15 April 2016
F. Hoffmann-La Roche Ltd
M. Perol: Advisory role for Roche and Pfizer. S. Peters: Education grants, provided consultation, attended advisory boards and/or provided lectures for the following organisations: Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Clovis, Eli Lilly, F. Hoffmann-La Roche, Janssen, Merck Sharp and Dohme and Merck Serono, Pfizer, Regeneron and Takeda. N. Pavlakis: Advisory role for Novartis, Takeda, Roche and Pfizer. S. Novello: Speakers Bureau for: Eli Lilly, BMS, MSD, F. Hoffmann-La Roche Ltd and Astra Zeneca. T. Karagiannis: Employee of, owns stocks in and has taken part in company-sponsored research for Genentech. A. Zeaiter: Employee of F.Hoffman-La Roche Ltd. R. Dziadziuszko: Substantive relationships with Novartis, Pfizer and BMS. All other authors have declared no conflicts of interest.
139PD - Patient-reported outcomes from FLAURA: Osimertinib versus standard of care (SoC) epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) (ID 396)
07:45 - 09:00 | Presenting Author(s): N. Leighl | Author(s): N. Karaseva, K. Nakagawa, B. Cho, J.E. Gray, T. Hovey, A. Walding, A. Rydén, S. Novello
In the phase 3 FLAURA trial (N = 556), osimertinib demonstrated superior efficacy to SoC EGFR-TKI as first-line treatment of EGFR mutation-positive advanced NSCLC.[1]
Patients in FLAURA completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (QLQ-C30) at baseline and then every 6 weeks, and Lung Cancer 13 items (QLQ-LC13) at baseline, then weekly for 6 weeks followed by every 3 weeks. Scores range from 0 to 100; higher scores represent greater symptom burden. A ≥10-point difference is considered clinically relevant. Pre-specified key symptoms were cough, dyspnoea, chest pain, appetite loss and fatigue.
Compliance with completing the questionnaire was ≥60% at all time points in both treatment arms. Baseline mean scores were similar in the osimertinib and SoC arms for cough (32.8 vs 33.5), dyspnoea (22.5 vs 25.0), chest pain (19.5 vs 20.8), appetite loss (22.7 vs 25.6) and fatigue (32.2 vs 35.8). Key symptoms improved in both arms from baseline over the first 9 months, with no significant differences in least-squares mean changes between the osimertinib and SoC arm (Table). Improvements in cough were seen from week 1 and were maintained throughout the first 9 months in both arms. QLQ-C30 functional and global health/quality of life scores improved from baseline in both arms, with no clinically relevant differences. Additional analyses are ongoing, including statistical significance testing and time to deterioration.Table:Change from baseline over 9 months in key patient-reported symptoms
Adjusted least-squares mean (95% CI)
Estimated treatment difference (95% CI)
Cough Osimertinib 248 –11.0 (–12.8, –9.2) 0.7 (–1.9, 3.2)
SoC 252 –11.7 (–13.5, –9.8)
Dyspnoea Osimertinib 248 –4.0 (–5.6, –2.5) 0.1 (–2.2, 2.4)
SoC 252 –4.1 (–5.7, –2.5)
Chest pain Osimertinib 248 –6.6 (–8.2, –5.0) –0.2 (–2.5, 2.1)
Appetite loss Osimertinib 252 –6.2 (–8.4, –3.9) –0.5 (–3.7, 2.7)
Fatigue Osimertinib 252 –5.5 (–7.5, –3.5) –0.8 (–3.6, 2.1)
Adjusted mean and estimated treatment differences obtained from a mixed-effects model for repeated measures. Model included patient (as a random effect), treatment, visit (as fixed effect and repeated measure), and treatment-by-visit interaction as explanatory variables, and the baseline symptom score as a covariate along with the baseline symptom score by visit interaction. The covariance structure for repeated measurements within the same patient was specified as unstructured. CI, confidence interval.
Key patient-reported symptoms in the FLAURA trial improved in both treatment arms from baseline over 9 months. Improvements in cough in the two arms were clinically relevant. [1]Soria JC et al. N Engl J Med doi: 10.1056/NEJMoa1713137.
N. Leighl: Research funding to University Health Network in 2015 - unrelated. Honoraria for unrelated CME from: BMS, AZ, Pfizer, Roche. K. Nakagawa: MSD K.K., A2 Healthcare Corp., in Ventiv Health Japan, Astellas Pharma Inc., Daiichi Sankyo Co., Ltd., Novartis Pharma K.K., AbbVie Inc., Quintiles Inc., Icon Japan K.K., Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., EP-CRSU Co., Ltd., Gritstone Oncology. Inc, Linical Co., Ltd., Eli Lilly Japan K.K., Eisai Co., Ltd., Bristol Myers Squibb Company, Taiho Pharmaceutical Co., Ltd., PAREXEL International Corp., Ono Pharmaceutical Co., Ltd. for Research Funding AstraZeneca K.K., Nichi-Iko Pharmaceutical Co., Ltd., Astellas Pharma Inc. Clinical Trial Co., Ltd, MSD K.K., Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb Company, Nippon Boehringer Ingelheim Co., Ltd., Eli Lilly Japan K.K., Novartis Pharma K.K., SymBio Pharmaceuticals Limited., Pfizer Japan Inc. for Honoraria Astellas Pharma Inc., Ono Pharmaceutical Co., Ltd. for Consulting or advisor role. J.E. Gray: Advisor to Astra Zeneca. T. Hovey: Working as a consultant (Phastar Statistician) for AstraZeneca. A. Walding: Employee and shareholder of AstraZeneca R&D. A. Rydén: Employee of AstraZeneca and has AstraZeneca stocks. S. Novello: Speaker bureau: Eli Lilly, AZ, BMS, MSD, Roche. All other authors have declared no conflicts of interest.
Invited Discussant 138PD and 139PD (ID 675)
07:45 - 09:00 | Presenting Author(s): S. Ekman
140PD - Complex epidermal growth factor receptor (EGFR) mutations and responses to tyrosine kinase inhibitors (TKIs) in advanced lung adenocarcinomas (ID 411)
07:45 - 09:00 | Presenting Author(s): B. Zhang | Author(s): S. Wang, J. Qian, W. Yang, F. Qian, J. Lu, Y. Zhang, R. Qiao, B. Han
Two or more different epidermal growth factor receptor (EGFR) mutations can be detected within a single tumor sample, which represents complex mutations. However, the frequency and efficacy of tyrosine kinase inhibitor (TKI) treatments for patients harboring these mutations are unknown.
From January 2011 to January 2017, patients diagnosed with EGFR mutation were screened. The effectiveness of TKIs in patients with complex mutations was retrospectively analyzed.
A total of 16,840 subjects were screened, with 5898 positive patients. 187 patients (3.2% of all EGFR mutant patients) had complex EGFR mutations with 95 of advanced lung adenocarcinoma patients were treated with TKIs. The objective response rate (ORR) for patients who had Del-19 + 21L858R (Group A, n = 27), Del-19/21L858R + atypical mutations (Group B, n = 28), double atypical mutations (Group C, n = 20) and complex mutations with primary drug-resistant pattern (Group D, n = 20) were 72.7%, 54.2%, 66.7% and 15.0%, respectively. Median progression free survival (PFS) in the four groups were 18.2 months (95% CI, 12.0 months to 24.4 months), 10.1 months (95% CI, 6.5 months to 13.7 months), 11.1 months (95% CI, 6.8 months to 15.4 months) and 1.4 months (95% CI, 0.2 months to 2.5 months), respectively.
These results suggest on the largest sample size that EGFR–TKI therapy is effective in patients with Del-19 + 21L858R, Del-19/21L858R + atypical mutations and double atypical mutations, but less effective in patients with primary drug–resistant pattern. Patients with the Del-19 + 21L858R mutations may therefore benefit more from treatment with first–generation TKIs.
Bo Zhang
141PD - A prospective study of molecular testing status in the EGFR mutation positive NSCLC patients with disease progression during EGFR TKI treatment (REMEDY study) (ID 167)
07:45 - 09:00 | Presenting Author(s): K. Kanai | Author(s): N. Yamamoto, N. Nogami, S. Atagi, H. Saka, N. Tashiro, T. Seto
Although EGFR tyrosine kinase inhibitors (EGFR-TKI) provide significant clinical benefit in patients with EGFR-mutant non–small cell lung cancer (NSCLC), approximately 50–60% of the patients will acquire resistance by the T790M mutation. Osimertinib is a third generation EGFR-TKI and standard of care for patients whose tumor developed the acquired resistance by T790M mutations during the prior EGFR-TKI treatments. Eligibility for treatment with osimertinib will be dependent on mutation status determined by a validated diagnostic test based on a tumor tissue or a plasma. In order to avoid the risk of false negative, the Japan Lung Cancer Society's guidance on the EGFR mutation test recommends prioritizing tissue sample over plasma sample. Moreover, in case of T790M negative by prior plasma test, it also recommends to re-confirm by tissue test if it can be obtained. We conducted this study to investigate the real world practice of sample collection and T790M testing around the time of plasma testing approval in Japan.
This is multicenter collaborative prospective observational study in Japan. Patients diagnosed with EGFR mutation-positive advanced NSCLC and whose progression of the disease (PD) was observed during EGFR-TKI treatment were enrolled. The primary endpoints are 1. the sample collection rate for EGFR T790M mutation test at PD, 2. EGFR T790M gene mutation testing and 3. the EGFR T790M detection rate. In addition, treatment information before and after PD were investigated.
In previously reported interim analysis of 111 patients, sample collection was performed in 104 cases (93.7%). Regarding collected sample type, tissue sample were collected from 19 patients, cytology sample from 14 patients and plasma sample from 71 patients. EGFR T790M mutation test was conducted in 103 cases (92.8%). T790M mutation detection rate in patients who were obtained adequate tissue sample were 43.8% (7/16) and higher than cytology (21.4%; 3/14) and plasma (22.5%; 16/71). Sixty-one percent (43/71) of the patients tested by plasma were ctDNA "non-shedders" (no detectable EGFR mutation).
In this presentation, we report final full results of total 243 registered cases.
UMIN ID; 000024928
This study was conducted by AstraZeneca KK
N. Yamamoto: Personal fees from AstraZeneca, during the conduct of the study; personal fees from Chugai Pharmaceutical, Boehringer Ingelheim, Eli Lilly, and Pfizer, outside the submitted work. N. Nogami: Personal fees from Meiji Seika Pharama., AstraZeneca KK, Pfizer Inc., Bristor-Myers Squibb, ONO Pharmaceutical Co., Ltd, Kyowa Hakko Kirin, TAIHO Pharmaceutical Co., Ltd, CHUGAI Pharmaceutical Co., Ltd, Eliy Lilly Japan and Boehringer Ingelheim. S. Atagi: Personal fees from AstraZeneca KK, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Lilly, Ono and Taiho and contract research with AstraZeneca KK, Boehringer Ingelheim, Chugai, Lilly, Merck Serono, Ono, Pfizer, Taiho and Yakult and consultant fee from AstraZeneca KK. H. Saka: Personal fees from AstraZeneca KK and contract research with AstraZeneca KK. and is a representative of NPO Central Japan Lung Study Group. N. Tashiro: Employee of AstraZeneca KK. T. Seto: Grants(G): Astellas, Bayer, Merck Serono, Novartis, Verastem. Personal fees(PF): BMS, Kissei, Kyowa Hakko Kirin, Nippon Kayaku, Ono, Roche, Sanofi, Showa, Sumitomo Dainippon, Taiho, Takeda and other 3. G and PF: AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, MSD, BI, Pfizer, Yakult. All other authors have declared no conflicts of interest.
142PD - Detection of EGFR mutations in cerebrospinal fluid of EGFR-mutant lung adenocarcinoma with brain metastases (ID 491)
07:45 - 09:00 | Presenting Author(s): L. Shi | Author(s): Z. Liu, J. Tang, H. Wu, L. Guo, M. Li, L. Tong, W. Wu, H. Tao, W. Wu
A large proportion of lung adenocarcinoma (LADC) with epidermal growth factor receptor (EGFR) activating mutation will develop brain metastases (BMs) throughout the course of their disease. BM lesions were hard to obtain, which resulted in poor understanding of resistance mechanisms of EGFR tyrosine kinase inhibitors (EGFR-TKIs) therapy in these patients. Liquid biopsy of cerebrospinal fluid (CSF) may provide potential information of intracranial lesions. Herein, we aimed to investigate the alternative detection of EGFR mutation status in CSF.
Between July 2014 and June 2017 in Beijing Chest Hospital, thirty LADC patients with BMs carrying activating EGFR mutation in their primary tumors determined by amplification-refractory mutation system (ARMS) assay were enrolled. Their matched CSF and plasma samples were collected. Droplet digital PCR assays (ddPCR) for EGFR mutations, including 19del, L858R, and T790M were developed using two millilitres CSF or plasma. The clinical response of intracranial objective response rate (iRR), intracranial progression-free survival (iPFS), and intracranial overall survival (iOS) from the time of diagnosis of BM were evaluated.
All of the included patients were Chinese and had been diagnosed with stage IV lung adenocarcinoma. Out of 30 patients, 21 were females and 9 males aged from 34 to 75 years old (median age of 58 years old). The majority (24/30) classified as good Eastern Cooperative Oncology Goup performance status (ECOG PS <2). In all of cases, CSF cytology were negative and examinations of cranial imaging showed no leptomeningeal metastases (LM). In ddPCR assays, EGFR mutations were detected in CSF of 10 patients (33.3%), including three cases with EGFR T790M mutations, and in plasma of 14 patients (46.7%), including six cases with EGFR T790M mutations. All EGFR T790M mutations were found during or after EGFR-TKIs treatments. Five patients with activating EGFR mutations in CSF achieved intracranial partial response (iPR) after treated with combination of first-generation EGFR-TKIs and whole brain radiotherapy (WBRT)/stereotactic radiosurgery (SRS). Three patients with EGFR T790M mutations in CSF achieved iPR after treated with second-line osimertinib. The median iOS and iPFS from the time of diagnosis of BM were 15.0 months and 11.0 months, respectively. The following Table shows the EGFR testing result in detail.Table: (Abstract 142PD)EGFR testing result
Primary Tissue EGFR Mutation(ARMS)
CSF EGFR Mutation
Plasma EGFR Mutation
1 19del WT T790M 0.3%
2 19del WT 19del
3 L858R L858R 37.9% L858R 2.0%
4 L858R WT WT
5 19del WT WT
6 L858R WT L858R/T790M 10.8%/26.5%
8 19del 19del 69.7% 19del/T790M 11.0%/7.0%
10 19del WT WT
12 L858R WT L858R/T790M 2.4%/0.2%
13 L858R L858R 32.8% WT
15 19del 19del/T790M 13.2%/0.5% 19del/T790M 14.4%/3.5%
16 L858R WT WT
17 L858R L858R/T790M 16.2%/2.0% L858R/T790M 8.1%/2.2%
19 19del 19del 43.3% 19del 14.9%
21 19del WT 19del 3.7%
22 19del 19del 21.8% 19del 7.4%
23 L858R WT L858R 20.5%
24 19del WT 19del 11.4%
27 L858R L858R 7.2% L858R 5.2%
28 19del 19del 6.9% WT
29 19del 19del/T790M 35.7%/12.1% WT
It was feasible to test EGFR mutation in CSF and plasma. CSF may serve as liquid biopsy of advanced LADC with BMs by detecting cfDNA within CSF to characterize EGFR mutations. For those advanced LADC with BMs harboring EGFR mutation, dynamic monitoring EGFR mutation status of CSF would be an appropriate choice.
Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
Beijing Municipal Administration of Hospitals Youth Talent Training Project (Grant No. QML20151502)
07:45 - 09:00 | Presenting Author(s): S. Ortiz-Cuaran
143PD - Competing central nervous system or systemic progression analysis for patients with EGFR mutation-positive NSCLC receiving afatinib in LUX-Lung 3, 6, and 7 (ID 561)
07:45 - 09:00 | Presenting Author(s): J.C. Yang | Author(s): Y. Wu, V. Hirsh, K. O'byrne, N. Yamamoto, S. Popat, A. Tamiya, A. Märten, M. Schuler
CNS metastases are known complications of advanced EGFRm+ NSCLC, thus, LUX-Lung (LL) trials investigating afatinib allowed enrolment of patients (pts) with brain metastases (BM). LL3, 6 and 7 previously demonstrated activity of afatinib in pts with BM, with the magnitude of progression-free survival (PFS) improvement with afatinib vs chemotherapy or gefitinib in pts with BM being similar to that observed in pts without BM (HR 0.54, 0.47, and 0.76 in LL3, 6 and 7, respectively).[1,2] PFS was significantly improved with afatinib vs chemotherapy in a combined analysis of LL3 and 6 in pts with asymptomatic BM (HR 0.50, p = 0.0297).[1] To investigate whether afatinib can prevent CNS progression or metastasis, competing risk analyses for the progression and metastasis pattern in the CNS or non-CNS region were carried out in pts with and without BM in LL3, 6 and 7.
Competing risk analyses were performed in pts with stage IIIB/IV EGFRm+ NSCLC who received afatinib 40 mg/d in LL3, 6 and 7. Analyses were performed separately for pts with baseline BM and without baseline BM. Risk of CNS progression vs non-CNS progression or death was calculated based on the cumulative frequency of the event of interest vs the competing risk event.
In pts with baseline BM receiving afatinib in LL3 and 6 (n = 48; median follow-up 10.3 mo), 31.3% had CNS progression vs 52.1% with non-CNS progression: cumulative incidence at 6 and 12 mo (CNS vs non-CNS) was 15.5% vs 17.7%, and 24.5% vs 24.4%, respectively. In pts without baseline BM receiving afatinib in LL3, 6 and 7 (n = 485; median follow-up 13.0 mo), risk of de novo CNS progression was very low (6.4%) compared with non-CNS progression (78.4%). Cumulative incidence at 6 and 12 mo (CNS vs non-CNS) was 1.3% vs 17.2%, and 2.6% vs 41.2%, respectively.
Competing risk analyses using data from LL3, 6 and 7 add to the existing evidence that support afatinib use in pts with EGFRm+ NSCLC and CNS metastases. Taken together, these results suggest afatinib delays the onset/progression of BM. 1. Schuler. J Thorac Oncol 2016;11:380–90 2. Park. Lancet Oncol 2016;17: 577–89
NCT00949650, NCT01121393, NCT01466660
J.C-H. Yang: Honoraria/advisory board: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene, Merrimack, Yuhan Pharma, BMS, Ono Pharma Daiichi Sankyo, Astrazeneca. Y-L. Wu: Honoraria: AstraZeneca, Roche, Eli Lilly, Pfizer, Sanofi. V. Hirsh: Advisory Board: BI. K. O'Byrne: Advisory board & Honoraria: Astrazeneca, BMS, Roche-Genentech, MSD, Pfizer, Boehringer-Ingelheim, Novartis Speaker bureau activities: Astrazeneca, BMS, Roche-Genentech, MSD, Pfizer, Boehringer-Ingelheim Travel to international conferences: Astrazeneca, BMS, Roche-Genentech, MSD, Pfizer, Boehringer-Ingelheim 3 patents –1 on novel drugs and 2 on biomarkers – IP held by University. N. Yamamoto: Membership on an advisory board or board of directors: BI, AZ, Chugai Corporate-sponsored research: BI. S. Popat: Membership on an advisory board or board of directors: BI. A. Tamiya: Grants from Ono Pharmaceutical, Bristol-Myers Squibb Received personal fees from Eli Lilly, Ono Pharmaceutical, Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb. A. Märten: Employment Boehringer Ingelheim. M. Schuler: Employment: Universität Duisburg-Essen, Universitätsklinikum Essen, Ruhrlandklinik Consultant (compensated): AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, Roche Consultant (not compensated): Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) Honoraries (CME presentations): Abbvie, Alexion, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly, MSD, Novartis Research funding (institution) Boehringer Ingelheim, Bristol Myers-Squibb, Novartis Pantent: Universität Duisburg-Essen.
144PD - Leptomeningeal metastases in EGFR-mutated non-small cell lung carcinoma: Management after tyrosine kinase inhibitors (ID 611)
07:45 - 09:00 | Presenting Author(s): R. Flippot | Author(s): E. Auclin, P. Biondani, E. Le Rhun, D. Planchard, C. Caramella, C. Le Pechoux, L. Lacroix, L. Mezquita, B. Besse
Leptomeningeal metastases (LM) in non-small-cell lung carcinoma (NSCLC) are associated with poor outcome. Tyrosine kinase inhibitors (TKIs) are active in LM+ EGFR mutated (EGFRm) patients (pts), but optimal patient's management after failure of TKIs is unknown.
We included consecutive pts with EGFRm NSCLC who had LM progression during first-line EGFR TKI, defined as diagnosis of LM during TKI treatment or progression of known LM after first-line TKI, treated in our institution. Clinical and pathological data were retrospectively collected. We evaluated overall survival (OS), progression-free survival (PFS), clinical response rate (CRR), and disease control rate (DCR) defined as clinical response or stable disease >2 months.
We included 66 pts treated between Apr. 2003 and Sept. 2016, with a median age of 54 years [26–79]; 51 (77%) were females; 56 (85%) non-smokers. Twenty-three tumors (35%) had exon 19 deletion, 23 (35%) L858R exon 21 mutation, 10 (15%) T790M mutation. Median number of previous lines was 2 [1–7], and 19 pts (29%) had additional intrathecal treatment. 2[nd] line TKI was given to 36 pts (55%): 19 (53%) received erlotinib, 10 (28%) high dose (HD) erlotinib (300 mg daily), 3 osimertinib, 4 other 1[st]/2[nd] generation TKI (3 gefitinib, 1 afatinib). Median PFS and OS from LM progression were 3 months (m) [CI95% 2–3] and 7 m [CI95% 3–16], respectively. CRR and DCR for 2nd-line TKI were 43% and 77%. Nine pts (25%) were alive at 10 m (6 erlotinib, 1 HD erlotinib, 2 osimertinib). Median OS for erlotinib, HD erlotinib, osimertinib and other 1[st]/2[nd] generation TKI were 8 m (CI 95% 7–16), 3 m (CI 95% 2-not reached (NR)), NR (CI 95% NR-NR), and 2.5 m (CI 95% 0-NR), respectively. Patients treated with erlotinib, of whom 79% received prior afatinib or gefitinib, had better OS compared to patients treated with other 1[st]/2[nd] generation TKI (8 m vs. 2.5 m, P = 0.04). CRR and DCR in patients with HD erlotinib were 40% and 60%, respectively, of whom 80% received prior erlotinib.
2[nd]-line TKI can increase survival in LM+ EGFRm NSCLC previously treated with TKI. Sequential erlotinib after prior gefitinib or afatinib seems to be a suitable strategy. Increasing erlotinib dose has demonstrated clinical benefit.
07:45 - 09:00 | Presenting Author(s): E. Wauters