- P. Garrido Lopez (Madrid, Spain)
- S. Novello (Orbassano, Italy)
- E. Smit (Amsterdam, Netherlands)
111O - Activity of larotrectinib in TRK fusion lung cancer
- A. Drilon (New York, NY, United States of America)
- A. Drilon (New York, NY, United States of America)
- S. Kummar (Stanford, CA, United States of America)
- V. Moreno (Madrid, Spain)
- J. Patel (Chicago, IL, United States of America)
- U. Lassen (Copenhagen, Denmark)
- L. Rosen (Los Angeles, CA, United States of America)
- B. Childs (Whippany, NJ, United States of America)
- S. Nanda (Whippany, NJ, United States of America)
- M. Cox (San Francisco, CA, United States of America)
- N. Ku (San Francisco, CA, United States of America)
- A. Farago (Boston, MA, United States of America)
Abstract
Background
Tropomyosin receptor kinases (TRK) fusions involving NTRK1, NTRK2 and NTRK3 genes occur in a diverse range of tumor types including lung cancer. Larotrectinib, the first FDA-approved selective TRK inhibitor, has demonstrated an overall response rate of 75% by independent central review across a broad range of tumor types (Drilon et al., NEJM 378:731-9, 2018). Here we report on the subset of lung cancer patients that have been treated with larotrectinib.
Methods
NSCLC patients with TRK fusion cancer detected by molecular profiling from two clinical trials (NCT02122913 and NCT02576431) were eligible. Larotrectinib (100 mg BID) was administered on a continuous 28-day schedule until withdrawal, unacceptable toxicity or disease progression. Efficacy was investigator assessed using RECIST version 1.1.
Results
As of July 30, 2018 eleven patients with metastatic lung adenocarcinoma were enrolled. Median age was 52 years (range 25 – 76). Eight patients had fusions involving NTRK1 and diverse fusion partners; EPS15 (n = 2), TPM3 (n = 2), IRF2BP2 (n = 2), TPR (n = 1), SQSTM1 (n = 1). Three patients had fusions involving NTRK3; fusion partners SQSTM1 (n = 2) and ETV6. Ten patients had prior systemic therapy (5 patients had 3 or more prior therapies) with best response on last prior therapy being 1 partial response and 4 stable disease. Seven patients were evaluable for response to larotrectinib. One patient had a complete response, 4 patients had a partial response, and 2 patients had stable disease (ORR 71%). The median time to response was 1.8 months. The duration of response ranged from 7.4+ months to 17.6+ months; the median duration of response was not reached. Two patients discontinued treatment due to disease progression and 1 withdrew consent. Four patients were on treatment less than 1 month and were non-evaluable for efficacy. Larotrectinib was well tolerated, with treatment related adverse events being predominantly grade 1 and grade 2.
Conclusions
Larotrectinib is highly active in lung cancer patients harboring NTRK gene fusions. These results strongly support the inclusion of NTRK gene fusions as part of routine molecular testing for patients with lung cancer.
Clinical trial identification
NCT02122913, NCT02576431.
Legal entity responsible for the study
Loxo Oncology Inc. Bayer AG.
Funding
Loxo Oncology Inc. Bayer AG.
Disclosure
A. Drilon: Honoraria: Ignyta, Loxo, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Genentech, Roche, Takeda, ARIAD, Millenium, Helsinn, Beigene, BerGenBio, Hengrui Therapeutics, Exelixis, Bayer, Tyra Biosciences; Research: Foundation Medicine. V. Moreno: Educational grant: Medscape/Bayer. U. Lassen: Honorarium: Bayer. L. Rosen: Research funding: Loxo Oncology. B.H. Childs, S. Nanda: Employee: Bayer Healthcare Pharmaceuticals. M.C. Cox, N.C. Ku: Employee: Loxo Oncology. A.F. Farago: Consulting: Bayer; Consulting, research funding: Loxo, AstraZeneca, Genentech, Pharmamar, AbbVie & Stemcentrx; Research funding: Ignyta, Merck, BMS. All other authors have declared no conflicts of interest.
112O - Circulating tumor (ct) DNA analysis to monitor response and resistance to ensartinib in patients (pts) with ALK+ non-small cell lung cancer (NSCLC)
- L. Horn (Nashville, TN, United States of America)
- L. Horn (Nashville, TN, United States of America)
- J. Whisenant (Nashville, TN, United States of America)
- H. Wakelee (Stanford, CA, United States of America)
- K. Reckamp (Duarte, United States of America)
- H. Qiao (Nashville, TN, United States of America)
- L. Du (Nashville, TN, United States of America)
- J. Hernandez (Kirkland, WA, United States of America)
- V. Huang (Nashville, TN, United States of America)
- S. Waqar (St. Louis, MO, United States of America)
- S. Patel (La Jolla, CA, United States of America)
- R. Sanborn (Portland, OR, United States of America)
- T. Shaffer (Kirkland, WA, United States of America)
- K. Garg (Kirkland, WA, United States of America)
- A. Holzhausen (Palm Beach Gardens, FL, United States of America)
- K. Harrow (Palm Beach Gardens, FL, United States of America)
- C. Liang (Palm Beach Gardens, FL, United States of America)
- L. Lim (Kirkland, WA, United States of America)
- M. Li (Kirkland, WA, United States of America)
- C. Lovly (Nashville, TN, United States of America)
Abstract
Background
Pts with anaplastic lymphoma kinase (ALK)-rearranged NSCLC have benefited from ALK tyrosine kinase inhibitors (TKIs); however, most pts eventually acquire resistance. Identification of resistance mutations informs subsequent therapy but has typically required invasive repeat biopsies. Here, we assessed the utility of ctDNA analysis and the ability to monitor response longitudinally and detect resistance mutations during therapy with ensartinib, a potent second-generation ALK TKI.
Methods
Blood samples were collected from pts at the start of and during treatment with ensartinib in the eXalt2 trial (NCT01625234). DNA from plasma samples was hybridized to a panel of probes using the Resolution Biosciences targeted hybrid-capture system. Archival tumor tissue from a subset of pts was analyzed for comparison. Efficacy assessments included response rate (RR) and median progression-free survival (mPFS).
Results
As of April 1, 2018, baseline plasma samples from 76 pts with ALK+ NSCLC were analyzed. Among these pts, 22% were ALK-TKI naive, 49% received prior crizotinib, and 29% received crizotinib and ≥ 1 second-generation ALK TKI. There was a high concordance rate (91%) between plasma and tissue analysis of ALK fusions. Among 69 efficacy-evaluable pts, the EML4-ALK variant 1 (V1) and V3 were detected at baseline in 17 pts (24%) and 7 pts (10%), respectively, and 12 pts (17%) had non-V1 or non-V3 fusions. Both RR and mPFS with ensartinib were more favorable in pts with V1 vs V3 fusions (9/17 [53%] vs 1/7 [14%] and 8.2 vs 1.9 months, respectively). The pooled RR of pts with other EML4-ALK variants was 7/12 (58%). Longitudinal plasma samples were analyzed in 11 pts. In general, reduced allelic frequencies (AFs) of ALK fusions were detected during clinical response, followed by increased AFs and/or the emergence of new mutations in ALK at or before disease progression.
Conclusions
Overall, the data suggest that plasma ctDNA analysis can potentially identify a subgroup of pts with ALK+ NSCLC who may derive clinical benefit from ensartinib. Furthermore, serial assessments of ctDNA during therapy offer a convenient method to track tumor response and identify the mutational landscape of acquired resistance.
Clinical trial identification
NCT01625234.
Editorial acknowledgement
Writing and editorial support was provided by Chrysalis Medical Communications funded by Xcovery Holding Company, LLC.
Legal entity responsible for the study
Xcovery Holding Company, LLC.
Funding
Xcovery Holding Company, LLC.
Disclosure
L. Horn: Consultant/Advisory board member: AbbVie, AstraZeneca, Bristol-Myers Squibb, Merck, Roche-Genentech, Xcovery; Commercial research support: Boehringer Ingelheim. H. Wakelee: Commercial research grants: Genentech/Roche, Novartis, Pfizer, Xcovery; Consultant/advisory board member: AstraZeneca, Genentech/Roche (uncompensated), Merck (uncompensated), Novartis (uncompensated), ARIAD (uncompensated); Commercial research grants to institution for conduct of clinical trial work: Genentech/Roche, Novartis, Pfizer, Lilly, Celgene, Astrazeneca/Medimmune, Exelixis, Clovis Oncology, BMS, Gilead, Pharmacyclics, ACEA biosciences, Merck, Xcovery. K.L. Reckamp: Consultant/advisory board member: ARIAD; Commercial research grants: Xcovery; Consultant/advisory board member: ARIAD Takeda, Exelixis, Guardant, Loxo, Genentech; Commercial research grants: Xcovery, AbbVie, Acea, Adaptimmune, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Guardant, Janssen, Loxo Oncology, Seattle Genetics, Takeda, Zeno. C.M. Lovly: Consultant: Pfizer, Novartis, AstraZeneca, Genoptix, Sequenom, ARIAD, Takeda, Foundation Medicine, Blueprints Medicine, Cepheid; Research funding: Novartis, AstraZeneca, Xcovery (through Vanderbilt University); Work in the CML laboratory is supported through the National Institutes of Health (NIH) and National Cancer Institute (NCI) R01CA121210 and P01CA129243, the Damon Runyon Foundation, the LUNGevity Foundation, the V Foundation, the Lung Cancer Foundation of America, and the International Association for the Study of Lung Cancer. CML was also supported through P30CA6848. J. Hernandez, T. Shaffer, K. Garg, L.P. Lim, M. Li: Employee, shareholder: Resolution Bioscience. S. Patel: Sci Ad Board member: AZ, BMS, Illumina, Tempus, Novartis; Research funding: BMS, Eli Lilly, Fate, Incyte, AZ/MedImmune, Merck, Pfizer, Roche/Genentech, Xcovery, Fate Therapeutics, Genocea, and Iovance; Research funds through UCSD. R.E. Sanborn: Consultant/advisory board member: ARIAD, Takeda. A. Holzhausen: Employee: Xcovery Holdings, Inc. K. Harrow, C. Liang: Employee, ownership interests (including patents): Xcovery Holding, Inc. All other authors have declared no conflicts of interest.
113O - Entrectinib in NTRK fusion-positive non-small cell lung cancer (NSCLC): Integrated analysis of patients (pts) enrolled in STARTRK-2, STARTRK-1 and ALKA-372-001
- L. Paz-Ares (Sevilla, Spain)
- L. Paz-Ares (Sevilla, Spain)
- R. Doebele (Aurora, CO, United States of America)
- A. Farago (Boston, MA, United States of America)
- S. Liu (Washington, DC, United States of America)
- S. Chawla (Los Angeles, CA, United States of America)
- D. Tosi (Boston, MA, United States of America)
- C. Blakely (South San Francisco, CA, United States of America)
- J. Krauss (Ann Arbor, MI, United States of America)
- D. Sigal (La Jolla, CA, United States of America)
- L. Bazhenova (San Diego, CA, United States of America)
- T. John (Heidelberg, VIC, Australia)
- B. Besse (Villejuif, CEDEX, France)
- J. Wolf (Cologne, Germany)
- T. Seto (FUKUOKA, Fukuoka, Japan)
- E. Chow-Maneval (San Diego, CA, United States of America)
- C. Ye (South San Francisco, CA, United States of America)
- B. Simmons (South San Francisco, CA, United States of America)
- G. Demetri (Boston, MA, United States of America)
- L. Paz-Ares (Madrid, Spain)
Abstract
Background
Neurotrophic receptor tyrosine kinase (NTRK) gene fusions lead to the expression of chimeric TRK proteins with constitutively activated kinase function, conferring oncogenic potential across several tumour types. Entrectinib is a CNS-active, potent inhibitor of TRKA/B/C and ROS1. We present integrated efficacy and safety data for entrectinib in NTRK fusion-positive (NTRK-FP) solid tumours focusing on pts with NSCLC.
Methods
Pts with locally advanced/metastatic NTRK-FP tumours (with or without baseline CNS disease) confirmed by nucleic acid-based methods, enrolled in global (>150 sites, 15 countries) phase 1/2 entrectinib trials (ALKA-372-001 [EudraCT 2012-000148-88], STARTRK-1 [NCT02097810], STARTRK-2 [NCT02568267]) were included. Disease burden was assessed per BICR using RECIST v1.1, after cycle 1 (4 wks) then every 8 wks. Primary endpoints: ORR, DOR by BICR. Secondary endpoints: PFS, OS, and safety.
Results
Outcomes in the total efficacy-evaluable population (n = 54; 10 tumour types, >19 histopathologies) are shown in the table; responses were seen in all tumour types, median PFS 11.2 mo. In the cohort of pts with NTRK-FP NSCLC (n = 10), BICR ORR was 70% (7/10). In NSCLC pts with CNS disease per investigator at baseline (n = 6), 4 had an intracranial response (2 complete, 2 partial); 1 had stable disease and 1 was not evaluable. In the safety population (68 pts with NTRK-FP solid tumors who received at least 1 dose of entrectinib), most treatment-related adverse events (TRAEs) were grade 1–2; grade 3: 32.4%, grade 4: 2.9%; no grade 5 TRAEs. TRAEs resulted in discontinuation in 4.4% and dose reduction in 39.7% of pts.
Conclusions
In this integrated analysis of global multicentre clinical trials, entrectinib was well tolerated and induced clinically meaningful, durable systemic and intracranial responses in pts with NTRK-FP solid tumours, including those with NSCLC. (Table).
Clinical trial identification
ALKA-372-001 = EudraCT 2012-000148-88 – start date: 2015, trials ongoing STARTRK-1= NCT02097810 – start date: 2014, active, not recruiting (last update 2018) STARTRK-2 = NCT02568267 – start date: 2015, recruiting (last updated 2018).
Editorial acknowledgement
Medical writing and editorial support was provided by Charlotte Kennerley, PhD of Gardiner-Caldwell Communications, Ashfield Healthcare Communications and sponsored by Roche in accordance with Good Publication Practice guidelines.
Legal entity responsible for the study
F. Hoffmann-La Roche.
Funding
Study Sponsor: Ignyta, Inc., a wholly owned subsidiary of F. Hoffmann-La Roche Ltd.
Disclosure
L. Paz-Ares: Honoraria: Lilly, MSD, BMS, Roche, PharmaMar, Merck, AstraZeneca, Novartis, BI, Celgene, Servier, Sysmex, Amgen, Incyte, Pfizer; Research: AZ, BMS, MSD; Advisory boards: Genomica; Scientific Chair/board member: Asociación Española Contra el Cáncer. R.C. Doebele: Sponsored research: Ignyta; Advisory boards: Roche, Ignyta, Takeda, AstraZeneca, Bayer; Stock ownership: Rain Therapeutics; Patent or biological material licensing fees: Ignyta, Abbott Molecular, Rain Therapeutics. A.F. Farago: Honoraria: Foundation Medicine, Clinical Care Options Oncology, Medical Learning Institute; Research: Ignyta, Loxo, AbbVie/Stemcentrx, PharmaMar, AZ, Novartis, Merck, BMS, Amgen; Consultant: Loxo, PharmaMar, AbbVie/Stemcentrx, Genentech, AZ, Bayer, Millennium. S.V. Liu: Research: Ignyta, Genentech, Pfizer, Threshold, Clovis, Corvus, Esanex, Bayer, OncoMed, Merck, Lycera, AZ, Molecular Partners, Rain Therapeutics; Advisory boards: Ignyta, Genentech, Pfizer, Takeda, Celgene, Lilly, Taiho, BMS, AZ, Regeneron, Merck. S.P. Chawla: Honoraria/research/Advisory boards: Amgen, Roche, GSK, Threshold Pharmaceuticals, CytRx Corporation, Ignyta, Immune Design, TRACON Pharma, Karyopharm Therapeutics, Sarc, Janssen. D. Tosi: Research funding: Novartis, Astellas, Janssen, Ipsen. C.M. Blakely: Research funding: Ignyta, Mirati, Novartis, Medimmune, Clovis. J.C. Krauss: Research funding: Boston Biomedical, AbbVie, Amgen, Isofol. D. Sigal: Advisory boards: Molecular Stethoscopye, Celularity, Curematch, Bayer; Research funding: Halozyme; Speakers bureau member: Celgene, Bayer; Stock ownership: BMS, Novartis, Halozyme. L. Bazhenova: Research funding: Beyongspring pharma; Stock ownership: EPIC Sciences; Advisory boards: Genentech, Takeda, AbbVie, Eli Lilly, Pfizer, AstraZeneca. T. John: Advisory boards: BMS, AstraZeneca, Boehringer Ingelheim, Takeda, Pfizer, Novartis, Merck, Ignyta, Roche. B. Besse: Research funding: AbbVie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma. J. Wolf: Advisory boards: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Ignyta, Lilly MSD, Novartis, Pfizer, Roche; Corporate sponsorship for research: BMS, MSD, Novartis, Pfizer. T. Seto: Honoraria/research: Astellas, AZ, Bayer, BMS, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Kissei, Kyowa HakkoKirin, Merck Serono, Mochida, MSD, Nippon, Novartis, BI, NipponKayakuOno, Pfizer, Roche, Sanofi, ShowaYakuhinKako, Taiho, Takeda, YakultHonsha, Verastem. E. Chow-Maneval: Employee: Ignyta. C. Ye, B. Simmons: Employee: Genentech. G.D. Demetri: Advisory boards: Blueprint Medicines, Merrimack Pharmaceuticals, G1 Therapeutics, Caris Life Sciences, Champions Oncology; Consultant: Novartis, Pfizer, EMD-Serono, Sanofi Oncology, Janssen Oncology, Ignyta, Roche, Loxo Oncology, Mirati Therapeutics, Epizyme, PharmaMar, Daiichi Sankyo, WIRB Copernicus Group, ZioPharm, Polaris Pharmaceuticals, M.J.Hennessey/OncLive, G1 Therapeutics, Caris Life Sciences, Champions Oncology, Bessor Pharmaceuticals, Erasca Pharmaceuticals; Consulting fees: Novartis, Pfizer, EMD-Serono, Sanofi Oncology, Janssen Oncology, Ignyta, Roche, Loxo Oncology, Mirati Therapeutics, Epizyme, PharmaMar, Daiichi Sankyo, WIRB Copernicus Group, ZioPharm, Polaris Pharmaceuticals, M.J.Hennessey/OncLive, Blueprint Medicines, Merrimack Pharmaceuticals, G1 Therapeutics, Caris Life Sciences, Champions Oncology; Research support: Bayer, Novartis, Pfizer, Janssen Oncology, Ignyta, Roche, Loxo Oncology, AbbVie, Epizyme, Adaptimmune, GlaxoSmithKline; Patent licensing fees: Novartis; Equity: Blueprint Medicines, Merrimack Pharmaceuticals, G1 Therapeutics, Caris Life Sciences, Champions Oncology, Bessor Pharmaceuticals, Erasca Pharmaceuticals.
114O - Potential resistance mechanisms using next generation sequencing from Chinese EGFR T790M+ non-small cell lung cancer patients with primary resistance to osimertinib: A multicenter study
- Y. Zhu (Zhenjiang, China)
- C. Xu (Fuzhou, China)
- W. Wang (Zhenjiang, China)
- Y. Zhu (Zhenjiang, China)
- Z. Yu (Fuzhou, China)
- H. Zhang (Xi'an, China)
- H. Wang (Beijing, China)
- J. Zhang (Beijing, China)
- W. Zhuang (Fuzhou, China)
- T. Lv (Nanjing, China)
- Y. Song (Nanjing, China)
Abstract
Background
Osimertinib (AZD9291) is a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated significant clinical benefits in patients with EGFR sensitizing mutations or T790M mutation. However, approximately 5% to 15% of patients with non-small-cell lung cancer (NSCLC) with EGFR T790M mutation has primary resistance to osimertinib treatment. The underlying mechanism is unknown.
Methods
A total of 117 patients with stage IIIb-IV EGFR-T790M NSCLC were undergoing tumor biopsies or blood withdrawing by the time of primary or acquiring to osimertinib, including FFPE samples, serum samples and serous effusions. We used targeted NGS to detect genes status of patients.
Results
Among 117 patients treated with osimertinib, 82.91% (97/117) developed acquired resistance, and 7.69% (9/117) had primary resistance. Using the specimens at the baseline, there were 3 (33.33%) patients with MET amplification, 1 (11.11%) patient with BCL2L11 loss (BIM deletion polymorphism), 1 (11.11%) patient with ERBB2 amplification, 1 (11.11%) patient with PTEN mutation, 1 (11.11%) patient with EZH2 mutation, and 2 (22.22%) patients with unknown status.
Conclusions
The mechanisms of primary resistance to EGFR-T790M may be highly heterogeneous. BCL2L11 loss, MET amplification, ERBB2 amplification, PTEN mutations, EZH2 mutations might contribute to molecular mechanisms of primary resistance to osimertinib in EGFR-T790M NSCLC. Further investigations are warranted to overcome these primary resistances.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
115O - Afatinib in EGFR TKI-naïve patients (pts) with locally advanced/metastatic NSCLC harbouring EGFR mutations: An interim analysis of a phase IIIB trial
- A. Passaro (Milan, Italy)
- A. Passaro (Milan, Italy)
- K. Laktionov (Moscow, Russian Federation)
- A. Poltoratskiy (St-Petersburg, Russian Federation)
- I. Egorova (St-Petersburg, Russian Federation)
- M. Hochmair (Vienna, Austria)
- M. Migliorino (Rome, Italy)
- G. Metro (Perugia, Italy)
- M. Gottfried (Tel Aviv, Israel)
- D. Tsoi (Murdoch, WA, Australia)
- G. Ostoros (Budapest, Hungary)
- S. Rizzato (Udine, Italy)
- G. Mukhametshina (Kazan, Russian Federation)
- M. Schumacher (Linz, Austria)
- S. Novello (Orbassano, Italy)
- R. Dziadziuszko (Gdansk, Poland)
- W. Tang (Ridgefield, CT, United States of America)
- L. Clementi (Milan, Italy)
- A. Cseh (Vienna, Austria)
- D. Kowalski (Warsaw, Poland)
- F. De Marinis (Milan, Italy)
Abstract
Background
First-line afatinib significantly improved progression-free survival (PFS) in pts with EGFR mutation-positive (EGFRm+) NSCLC (including uncommon mutations) vs chemotherapy (CT) in the LUX-Lung (LL) 3/6 trials (median 11.1 vs 6.9 mos; HR 0.58/11.0 vs 5.6 mos; HR 0.28) and vs gefitinib in LL7 (median 11.0 vs 10.9 mos; HR 0.73). However, in real-world (RW) practice CT remains a first-line choice. Here, we report an interim analysis of a Phase IIIb study of afatinib in treatment-naïve or CT pre-treated pts with EGFRm+ NSCLC, similar to RW practice.
Methods
EGFR TKI-naïve pts with locally advanced/metastatic EGFRm+ NSCLC and ECOG PS 0–2 received 40 mg/day afatinib (starting dose). Dose reduction was permitted (to minimum 20 mg/day). Primary endpoint: adverse events (AEs) in a descriptive fashion. Efficacy was also assessed.
Results
At data cut-off (30 April 2018), 479 pts were enrolled and treated with afatinib (Caucasian/Asian/other: 97%/2%/<1%; male/female: 34%/66%; 1st/2nd/≥3rd-line therapy: 78%/17%/5%; ECOG PS 0/1/2: 36%/57%/8%; brain metastases: 17%; common/uncommon mutations: 87%/13%). Median time on afatinib was 359 days. The most common grade ≥3 afatinib-related AEs were diarrhoea (16%) and rash (11%). AEs led to dose reduction in 258 (54%) pts (most frequently diarrhoea 25%; rash 11%) and to afatinib discontinuation in 105 (22%) pts (most frequently diarrhoea 3% [rash 0.8%]). Afatinib-related serious AEs occurred in 39 (8%) pts. Time to symptomatic progression (TTSP) and PFS are shown in the table. Objective response rate and disease control rate were 46% and 86%, respectively.
Conclusions
Interim analysis of this study, which included pts treated with afatinib in later lines, and pts with ECOG PS 2, brain metastases and/or uncommon mutations, indicates a predictable and manageable safety profile for afatinib, consistent with the pivotal LL trials. Interim efficacy findings are encouraging, with a median TTSP of 14.9 months.
Clinical trial identification
NCT01853826.
Editorial acknowledgement
Robert Lorence of Boehringer Ingelheim assisted in the study concept, design and data analysis. Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Jessica Sturgess of GeoMed, an Ashfield company, part of UDG Healthcare plc, during the development of this abstract.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim.
Disclosure
M. Hochmair: Honoraria for speakers’ bureau, advisory role: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, MSD, Novartis, Pfizer, Roche. M.R. Migliorino: Board of directors, consulting fees: Boehringer Ingelheim, Roche, MSD, Bristol-Myers Squibb, AstraZeneca, Pfizer; Honoraria: Boehringer Ingelheim, Roche, MSD, Bristol-Myers Squibb, AstraZeneca, Pfizer, Gentili. S. Rizzato: Honoraria for Advisory board: AbbVie. G.Z. Mukhametshina: Employment: Republic Clinical Oncology Dispensary. S. Novello: Honoraria for speaker bureau/advisory roles: Eli Lilly, Celgene, AstraZeneca, Boehringer Ingelheim, MSD, Roche, Bristol-Myers Squibb. R. Dziadziuszko: Honoraria: Roche, Pfizer, Boehringer Ingelheim, AstraZeneca, Foundation Medicine, Novartis. W. Tang, L. Clementi, A. Cseh: Employment: Boehringer Ingelheim. F. De Marinis: Advisory council/committee membership: Roche, Pfizer Honoraria: Roche, Bristol-Myers Squibb, AstraZeneca; Grants/funds: Boehringer Ingelheim. All other authors have declared no conflicts of interest.
196O - STELLAR: Final updated results of a phase II trial of TTFields with chemotherapy for unresectable malignant pleural mesothelioma
- G. Ceresoli (Bergamo, Italy)
- G. Ceresoli (Bergamo, Italy)
- J. Aerts (Rotterdam, Noord Brabant, Netherlands)
- R. Dziadziuszko (Gdańsk, Poland)
- S. Cedres (Barcelona, Spain)
- B. Hiddinga (Groningen, Netherlands)
- J. Van Meerbeeck (Edegem, Belgium)
- M. Mencoboni (Genova, Italy)
- D. Planchard (Villejuif, France)
- A. Chella (Pisa, Italy)
- L. Crinò (Meldola, (PG), Italy)
- M. Krzakowski (Warsaw, Poland)
- J. Madrzak (Gdańsk, Poland)
- R. Ramlau (Poznan, Poland)
- F. Grosso (Alessandria, Italy)
Abstract
Background
Tumor Treating Fields (TTFields), an anti-mitotic, regional treatment approved for glioblastoma utilizes low intensity, alternating electric fields delivered non-invasively to the tumor using a portable medical device. In-vitro, human mesothelioma cells were highly susceptible to TTFields.
Methods
The trial accrued 80 patients with unresectable, previously untreated mesothelioma. Patients were treated with continuous 150 kHz TTFields (>18h/day) in combination with pemetrexed and cisplatin or carboplatin. Inclusion criteria included ECOG PS of 0-1 and pathologically proven mesothelioma. The primary endpoint was overall survival (OS). A visual analog scale was used to assess EOCG performance status and cancer-related pain assessed until disease progression. The sample size provided 80% power with two-sided alpha of 0.05 to detect an increase in median OS of 5.5 months compared to historical controls (Vogelzang, JCO 2003).
Results
All 80 patients had a minimum follow up of 12 months. Median age was 67 (range 27-78), 84% were male and 44% (35 patients) had an ECOG PS of 1. 66% (53 patients) had epithelioid histology, similar to the Vogelzang study. Median OS was 18.2 months (95% CI 12.1-25.8) versus 12.1 months in the historical control. Median OS for epithelioid patients was 21.2 months (95% CI 13.2-25.8). ECOG score was stable during the first year of follow up. Median time to deterioration in performance status was 13.1 months. Average score of pain was lower compared to baseline during the first 7 months of the treatment and was higher later on the study, with a median time to a clinical significant 33% increase in pain of 8.4 months. No device-related serious adverse events (AEs) were reported. Expected TTFields-related dermatitis was reported in 46% (37 patients). Four patients (5%) had grade 3 dermatitis.
Conclusions
The study met primary endpoint of significant extension of overall survival in previously untreated mesothelioma patients. TTFields was not associated with a decrease in performance status or an increase in pain for the duration of TTFields use. TTFields in combination with chemotherapy is efficacious in malignant pleural mesothelioma compared to historical data.
Clinical trial identification
NCT02397928.
Legal entity responsible for the study
Novocure.
Funding
Novocure.
Disclosure
G.L. Ceresoli, F. Grosso: Travel funds: Novocure. All other authors have declared no conflicts of interest.