EGFR inhibitor versus chemotherapy as adjuvant treatment for locally-advanced EGFR-mutant non-small cell lung cancer

abstracts

Annals of Oncology 1470P

Table: 1469P Pre- and post-treatment mean (stdev) sum of variant allele fraction by response category

First real life data on durvalumab after definitive concomitant chemoradiotherapy (cCRT) in unresectable stage (St) III non-small cell lung cancer (NSCLC) in France: Analysis of 591 patients (pts) enrolled in the French cohort (c) temporary authorization of use (ATU) S. Bota Ouchlif2, P. Merle3, E. Pichon4, A.T. Stancu5, C. Chouaid6, C. Sire7, s8, A. Lagrange9, M. Sabatini10, G. Eberst11, P. Boisselier12, A. Gourion13, Lahouegue13, K. Belkhiria14, I. de La Porte14, M. Urbieta14, F. Mornex15,

Among pts with St III unresectable NSCLC, only 15% are alive at 5 years l Standard of Care (SoC) of definitive cCRT. Durvalumab, a human anti-PD-L1 antibody, demonstrated efficacy in PFS and OS and was Europe on September 2018 for the treatment of St III unresectable NSCLC  1% and without progression after CRT. ATU permits the access to nes for pts without alternatives before a market authorization is

Clinical trial identification: NCT02099058. Editorial acknowledgement: Iratxe Abarrategui, PhD, CMPP, from Aptitude Health, The Hague, Netherlands; funded by AbbVie. Legal entity responsible for the study: AbbVie Inc. Funding: AbbVie Inc. Disclosure: R.S. Heist: Advisory / Consultancy: Apollomics; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Tarveda Therapeutics; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): Peregrine Pharmaceuticals; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Millennium; Research grant / Funding (institution): Debiopharm Group; Research grant / Funding (institution): Corvus Pharmeceuticals; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Agios; Research grant / Funding (institution): Pfizer. M. Motwani: Shareholder / Stockholder / Stock options, Full / Parttime employment: AbbVie. L. Naumovski: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. J. Wu: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. B.A. Bach: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. X. Lu: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. K. Kelly: Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Regeneron; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AbbVie; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: EMD Serono; Honoraria (self), Advisory / Consultancy: Merck; Advisory / Consultancy: Pfizer; Licensing / Royalties, web information resource : UpToDate; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): Transgene; Research grant / Funding (institution): Lycera.

ab was administrated to pts as a 60 min intravenous infusion at 2 weeks for a maximum of 12 months, or discontinuation due to proAdverse Events (AE) or switch to commercial drug. Pts characteristics were prospectively collected during cATU. March 26th to October 28th 2018, 188 sites requested a cATU for 591 pts ectable NSCLC who did not progress after cCRT, independently of status. 561 pts were treated by Durvalumab (27 pts were treated with the drug & 3 pts were lost to follow-up). 71.6% of pts were men, median age years. 51.7% of tumours were adenocarcinoma. 40.5% of pts were in St in St IIIB and 6.2% in St IIIC. All pts were treated with platinum-based a median dose of 66 Gy [45.0-74.0] and 54% with cisplatin-based chemoresponse to cCRT was partial response for 78.5% of pts, complete 6.3% and stable disease for 15.2%. By January 2019, 82.1 % of pts were still and 46.3% pts treated more than 6 months. Overall, drug related in 17.3% of pts including 8.2% serious AEs. Most common Durvalumab related AEs (all grades) were hyperthyroidism (1.2%) and pneumonitis (1.1% or n ¼ 6, including one death). Discontinuation occurred in 17.8% of pts, of which 5.2% were Durvalumab related. Conclusions: These data confirm that Durvalumab has a manageable safety profile in real-life practice. Enrollment of 591 pts in 7 months highlights the high unmet need for stage III unresectable NSCLC pts and supports Durvalumab treatment as the new SoC. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: V. Avrillon: Advisory / Consultancy: Bristol-Myers Squibb (BMS); Travel / Accommodation / Expenses, congress invitation: Merck Sharp & Dohme (MSD); Advisory / Consultancy: AbbVie; Advisory / Consultancy: Bristol-Myers Squibb (BMS); Advisory / Consultancy: AbbVie; Travel / Accommodation / Expenses: MSD. E. Pichon: Travel / Accommodation / Expenses: Bristol-Myers Squibb (BMS); Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Merck Sharp & Dohme (MSD). A.T. Stancu: Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Bristol-Myers Squibb (BMS). C. Chouaid: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Clovis; Advisory / Consultancy: Glaxosmithkline; Advisory / Consultancy: Hoffmann-La Roche; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Amgen. A. Lagrange: Travel / Accommodation / Expenses: Hoffmann-La Roche; Travel / Accommodation / Expenses: Takeda; Travel / Accommodation / Expenses: Bristol-Myers Squibb (BMS). M. Sabatini: Travel / Accommodation / Expenses: Sos Oxygene; Advisory / Consultancy: BMS; Travel / Accommodation / Expenses: Boehringer Ingelheim. G. Eberst: Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: boehringer ingelheim. P. Boisselier: Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: MSD; Honoraria (self): Merck Serono; Honoraria (self): BMS; Honoraria (self): Roche. All other authors have declared no conflicts of interest.

1471P

EGFR inhibitor versus chemotherapy as adjuvant treatment for locally-advanced EGFR-mutant non-small cell lung cancer

P. Xie1, W. Tang1, X. Li1, Y. Dong1, X. Sun1, J. Zhang2, J. Yu1 Oncology, Shandong Cancer Hospital and Institute, Jinan, China, 2Oncology, Linshu People’s Hospital, Linyi, China

1

Background: Cisplatin-based chemotherapy as adjuvant therapy for resected NSCLC has reached its plateau, and was limited by high risk of recurrence and significant

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Centre Le´on Be´rard, Lyon, France, 2Pneumology, Hop. Charles France, 3Pneumology, Centre Jean Perrin, Clermont-Ferrand, France, CHRU Bretonneau, Tours, France, 5Hoˆpital de Jour, Institut SainteSec. 2, France, 6Pneumology, CH Intercommunal de Cre´teil, Cre´teil, Oncology, Centre Hospitalier de Bretagne Sud - Hoˆpital du Scorff, 8 Medical Oncology, Hoˆpital Avicennes, Bobigny, France, 9Medical Georges-Franc¸ois Leclerc, Dijon, France, 10Pneumology, Centre la Coˆte Basque, Bayonne, France, 11Pneumology, CHU Besanc¸on, Hoˆpital Besanc¸on, France, 12Radiotherapy, ICM Regional Cancer Institute of Montpellier, France, 13Regulatory Affairs, AstraZeneca, Courbevoie, France, AstraZeneca, Courbevoie, France, 15Radiation Oncology, CHU Lyon ´nite, France, 16Thoracic Oncology, Institut Curie, Paris, France

abstracts

1472P

Table: 1472P Median TTSP,

Median PFS,

Afatinib in EGFR TKI-naı¨ve patients with EGFR mutation-positive (EGFRm1) NSCLC: Interim analysis of a phase IIIb, multi-national, open-label study

F. de Marinis1, K.K. Laktionov2, A. Poltoratskiy3, I. Egorova4, M. Hochmair5, A. Passaro1, M.R. Migliorino6, G. Metro7, M. Gottfried8, D. Tsoi9, G. Ostoros10, S. Rizzato11, G.Z. Mukhametshina12, M. Schumacher13, S. Novello14, W. Tang15, L. Clementi16, A. Cseh17, D.M. Kowalski18 1 Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy, 2 Carcinogenesis Institute of N.N Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russian Federation, 3Department of Preclinical and Clinical Trials, Petrov Research Institute of Oncology, St Petersburg, Russian Federation, 4Thoracic Department, Clinical Oncology Dispensary, St Petersburg, Russian Federation, 5Respiratory Oncology Unit, Otto Wagner Hospital, Vienna, Austria, 6 Department of Oncological Pneumology, San Camillo-Forlanini Hospital, Rome, Italy, 7 Department of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy, 8Department of Oncology, Tel Aviv University, Tel Aviv, Israel, 9Department of Oncology, St John of God Murdoch Hospital, Murdoch, Australia, 10Department of Tumor Biology, National Koranyi Institute for Pulmonology, Budapest, Hungary, 11 Department of Oncology, Azienda Sanitaria-Universitaria Integrata, Udine, Italy, 12 State Healthcare Institute Republican Clinical Oncological Center, Ministry of Health of the Republic of Tatarstan, Kazan, Russian Federation, 13Thoracic Centre, Ordensklinikum Elisabethinen, Linz, Austria, 14Oncology Department, University of Turin, Turin, Italy, 15Statistics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA, 16Clinical Operations, Boehringer Ingelheim Italia S.p.A., Milan, Italy, 17Department of Medical Affairs, Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria, 18 Department of Lung Cancer and Thoracic Oncology, Oncology Centre and Institute, Warsaw, Poland Background: First-line afatinib demonstrated significantly improved PFS in patients with EGFRmþ NSCLC vs chemotherapy in LUX-Lung 3/6 (HR, 95% CI: 0.58, 0.43– 0.78/0.28, 0.20–0.39) and vs gefitinib in LUX-Lung 7 (0.73, 0.57–0.95). Given the strict inclusion criteria of randomised controlled trials, it is important to support findings with evidence from real-world studies and broader patient populations. We report interim results of an open-label, Phase IIIb study of afatinib in the treatment of EGFRmþ NSCLC. Methods: EGFR TKI-naı¨ve patients with locally advanced/metastatic EGFRmþ NSCLC and ECOG PS 0–2 received afatinib 40 mg/day. Dose reduction was permitted (minimum 20 mg/day). Primary endpoint: adverse events (AEs; descriptive fashion). Efficacy was also assessed. Results: A total of 479 patients were enrolled/treated (data cut-off 30 April 2018). Caucasian: 97%; 1st/2nd/3rd-line therapy: 78%/17%/5%; ECOG PS 0–1/2: 92%/8%; common/uncommon only mutations: 87%/13%; brain metastases: 17%. Median time on afatinib was 359 days. Objective response/disease control rates were 46%/86%. Other efficacy outcomes are shown in Table. The most common grade 3 drug-related AEs (DRAEs) were, n (%): diarrhoea, 77 (16) and rash, 51 (11). 258 (54) patients had AEs leading to dose reduction (most commonly due to diarrhoea, 119 [25] or rash, 53 [11]) and 37 (8) had DRAEs leading to discontinuation (diarrhea, 16 [3]; all others, 4 [<1]). 39 (8) patients had serious DRAEs.

v598 | NSCLC, Locally Advanced

Funding: Boehringer Ingelheim. Disclosure: F. de Marinis: Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: AstraZeneca; Research grant / Funding (self): Boehringer Ingelheim; Honoraria (institution), Research grant / Funding (self): Merck Sharp and Dohme. A. Poltoratskiy: Advisory / Consultancy, Speaker Bureau / Expert testimony: GCP.center Russia. M. Hochmair: Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Merck Sharp and Dohme; Advisory / Consultancy: Novartis; Honoraria (self): Pfizer; Honoraria (self), Advisory / Consultancy: Roche. A. Passaro: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck Sharp and Dohme; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Roche; Advisory / Consultancy: Dako. M.R. Migliorino: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy: Merck Sharp and Dohme. G.Z. Mukhametshina: Advisory / Consultancy: Association of oncologists of Russian Federation; Full / Part-time employment: State Autonomous Healthcare Institution «Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan». M. Schumacher: Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Merck Sharp and Dohme; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: AstraZeneca. S. Novello: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp and Dohme; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene;

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toxicities. The clinical value of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resected non-small cell lung cancer (NSCLC) harboring EGFR mutations remains controversial. In this study, we performed a meta-analysis to evaluate the role of EGFR inhibitors as adjuvant therapy for targeted patients. Methods: Studies were identified via an electronic search on Pubmed, EMBASE, ISI Web of Science, ScienceDirect, SpringerLink, The Cochrane library and so on. Pooled odds ratio (OR) for disease-free survival (DFS) and overall survival (OS) were calculated for meta-analysis. Registration number: PROSPERO (CRD42018093144). Results: There were 11 trials (1,152 resected NSCLC patients with EGFR sensitive mutations) in this meta-analysis. Results showed that adjuvant treatment with EGFRTKIs can prolong both OS and DFS when compared to treatment without TKIs as adjuvant therapy (OS: Figure 1, OR, 0.63; 95% CI, 0.46 to 0.87, P ¼ 0.004; heterogeneity I2¼61%, P ¼ 0.008; DFS: OR, 0.56; 95% CI, 0.43 to 0.72, P < 0.00001; heterogeneity I2¼37%, P ¼ 0.1). Results of predefined subgroup analyses in this meta-analysis suggested a greater DFS with EGFR-TKI mono compared with chemotherapy, whereas the OS benefit failed to show a similar difference between the two arms (p ¼ 0.3). And we also find that treatment with EGFR-TKI plus chemotherapy was associated with significantly longer DFS as well as OS than chemotherapy mono in patients with completely resected EGFR-mutant NSCLC. Conclusions: Adjuvant EGFR-TKIs may be a potential treatment option compared to adjuvant chemotherapy in completed resected patients with EGFR mutation-positive NSCLC. This project was supported by the National Natural Science Foundation of China (Grant No. 81502667), Key Research and Development Plan of Shandong, China (Grant No. 2016GSF201167). Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Annals of Oncology