Found 4 Presentations For Request "flaura"

Presidential Symposium I Proffered Paper session

LBA5_PR - Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): Final overall survival analysis (ID 567)

Presentation Number
LBA5_PR
Lecture Time
17:56 - 18:08
Speakers
  • Suresh S. Ramalingam (Atlanta, United States of America)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
16:30 - 18:20

Abstract

Background

Osimertinib is a 3rd-generation, irreversible, oral EGFR-TKI that potently and selectively inhibits both EGFR-mutated (EGFRm) and EGFR T790M resistance mutations, and has demonstrated efficacy in NSCLC CNS metastases. In the phase III FLAURA study (NCT02296125), osimertinib resulted in significant progression-free survival (PFS) benefit (primary endpoint; datacut off [DCO] 12 June 2017) over comparator EGFR-TKI (HR 0.46, p < 0.001). Overall survival (OS) data were immature (25% maturity) at that time. Here, we report the final OS analysis (58% maturity).

Methods

Eligible patients (pts): ≥18 years (Japan: ≥20), treatment-naïve with Ex19del/L858R EGFRm advanced NSCLC; WHO performance status 0–1. Pts with stable CNS metastases not requiring steroids for ≥2 weeks were allowed. Pts were randomised 1:1 to osimertinib 80 mg once daily (qd) orally (po) or comparator EGFR-TKI (gefitinib 250 mg qd/erlotinib 150 mg qd po), stratified by mutation status (Ex19del/L858R) and race (Asian/non-Asian). Crossover was allowed for pts in the comparator EGFR-TKI arm upon central confirmation of progression and T790M positivity. Primary endpoint: PFS by RECIST v1.1, per investigator. OS was a secondary endpoint. DCO 25 June 2019.

Results

Globally, 556 pts were randomised to osimertinib (n = 279) or comparator EGFR-TKI (n = 277). Per study protocol, 70 (25%) pts crossed over from comparator EGFR-TKI to osimertinib. Osimertinib significantly improved OS vs comparator EGFR-TKI. All causality AEs, per investigator: osimertinib, 98% (grade ≥3, 42%); comparator EGFR-TKI, 98% (grade ≥3, 47%). AEs leading to discontinuation: osimertinib, 15%; comparator EGFR-TKI, 18%. The safety profile appears consistent with previously reported data.

LBA5_PR

Efficacy outputOsimertinib n = 279Comparator EGFR-TKI n = 277
OS hazard ratio0.799 (0.641, 0.997); p = 0.0462
(95.05% confidence interval)
Median OS, months38.631.8
(95% confidence interval)(34.5, 41.8)(26.6, 36.0)
Deaths, total pts (%)155 (56)166 (60)
Median follow-up for OS in all pts, months35.827.0
Median follow-up for OS in censored* pts, months43.143.1
12-month survival rate, %8983
(95% confidence interval)(85, 92)(77, 87)
24-month survival rate, %7459
(95% confidence interval)(69, 79)(53, 65)
36-month survival rate, %5444
(95% confidence interval)(48, 60)(38, 50)

OS for patients in the full analysis set was analysed using a log rank test (stratified by race and mutation type) for generation of the p-value and using the Breslow approach for handling ties. The median OS with 95% confidence intervals were calculated by Kaplan Meier technique. For statistical significance, a 2-sided p-value of less than 0.0495, as determined by the O’Brien-Fleming approach was required due the previous interim analysis.*Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive.

Conclusions

Osimertinib provided a statistically significant and clinically meaningful improvement in OS vs comparator EGFR-TKI in first-line pts with EGFRm advanced NSCLC.

Clinical trial identification

NCT02296125.

Editorial acknowledgement

Natalie Griffiths, PhD, from iMed Comms, an Ashfield Company; funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

S.S. Ramalingam: Honoraria (self), Advisory / Consultancy: AstraZeneca, Amgen, Bristol-Myers Squibb, Merck, Roche/Genentech, Loxo, Nektar, Tesaro; Research grant / Funding (institution): AstraZeneca, Amgen, Bristol-Myers Squibb, Merck, Tesaro, Advaxis, Takeda. J.E. Gray: Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Takeda; Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, Celgene, Takeda; Research grant / Funding (institution): Array, Merck, AstraZeneca, Genentech, Boehringer Ingelheim, Bristol-Myers Squibb. Y. Ohe: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca, Chugai, Dainippon Lilly, Ono, BMS Japan, Daiichi Sankyo, BI, Bayer, Ignyta, Pfizer, MSD, Taiho, Novartis, Kyorin, Kyowa Hakko Kirin, Takeda, Celltrion, Kissei, Amgen, Janssen, ROXO. B.C. Cho: Honoraria (institution), Advisory / Consultancy: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Pfizer, Eli Lilly, Takeda; Speaker Bureau / Expert testimony: Novartis; Research grant / Funding (institution): Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD; Licensing / Royalties: Champions Oncology; Shareholder / Stockholder / Stock options: TheraCanVac Inc.. J. Vansteenkiste: Research grant / Funding (institution): MSD; Advisory / Consultancy: Apotex, AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Roche; Speaker Bureau / Expert testimony: AstraZeneca, BMS, MSD, Roche. C. Zhou: Honoraria (self): Roche, Eli Lilly, Boehringer Ingelheim, Merck, Hengrui and Qiru. B. Chewaskulyong: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca. R. Shah: Honoraria (self), Travel / Accommodation / Expenses: Boehringer Ingelheim, Roche, AstraZeneca. P. Cheema: Honoraria (self), Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Merck, Takeda, Novartis, Genomic Health, Pfizer. M. Tiseo: Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, MSD, Boehringer Ingelheim, Takeda; Research grant / Funding (institution): AstraZeneca. T. John: Advisory / Consultancy: Roche, Bristol-Myers Squibb, Merck, Ignyta, AstraZeneca, Takeda, Boehringer Ingelheim, Pfizer. F. Imamura: Honoraria (self), Research grant / Funding (institution): AstraZeneca. R. Hodge: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. Y. Rukazenkov: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. J. Soria: Advisory / Consultancy: AstraZeneca, Astex, Clovis, GSK, GamaMabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, PharmaMar, Pierre Fabre, Roche/Genentech, Sanofi, Servier, Symphogen, and Takeda; Shareholder / Stockholder / Stock options: AstraZeneca, Gritstone; Full / Part-time employment: AstraZeneca. D. Planchard: Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, MedImmune, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Research grant / Funding (institution): AstraZeneca, Bristol-Myers Squibb, AbbVie, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo; Travel / Accommodation / Expenses: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim , Roche, Merck,Novartis, prIME Oncology, Pfizer. All other authors have declared no conflicts of interest.

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Poster Display session 1 Poster Display session

1533P - Treatment patterns of EGFR mt+ NSCLC IV pts: Real-world data of the NOWEL network (ID 2941)

Presentation Number
1533P
Lecture Time
12:00 - 12:00
Speakers
  • Julia Roeper (Berlin, Germany)
Session Name
Poster Display session 1
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
12:00 - 13:00

Abstract

Background

The percentage of pts switching from 1st gen TKI in 1st line to 3rd gen TKI in 2nd line seems to be low with 30% and it is questionable whether these data represent real world treatments. Therefore, we investigated the treatment pattern and especially the attrition rate between 1st and 2nd line therapy in EGFR mt+ pts from the NOWEL network.

Methods

A retrospective study of 1539 pts with non-squamous NSCLC IV was accomplished. 965/1536 (63%) pts were tested for EGFR mt+ between 2009-2018. 148/965 (15%) pts with an EGFR mt+ were identified. To calculate PFS and OS we used Kaplan Meier methods and the log rang test for p-values.

Results

Baseline characteristics of 148 EGFR mt+ pts: median age 65 yrs; 64% female (n = 95/148); 64% never/light smoker (n = 94/148). 135/148 pts (91%) carried an EGFR mt+ either del19 (n = 81) or L858R (n = 55). 144/148 pts were treated with TKI on 1st or 2nd line (after chemotherapy) and 4 pts received no therapy at all. 14/144 pts are still on 1st line, 9 pts were lost to follow-up and 3 pts died while on 1st line therapy. We identified 118/144 candidates for 2nd line therapy (because of progression on 1st line TKI) and only 84/118 (70%) pts received a 2nd line therapy. 30% (36/118) of pts did not receive a 2nd line therapy because of bad PS (n = 26), pts refusal (n = 2), fast progression (n = 6) and death (n = 2). After accessibility of 3rd gen TKI 72 pts were candidates for 2nd line treatment and 51/71 pts (71%) received a 2nd line therapy. MOS of pts receiving 2nd line therapy after access to 3rd gen TKI was 35 mo for pts with 2nd line therapy vs. 10 mo without 2nd line (p < 0.000). 32/51 pts (63%) were tested for T790M and 20/32 (62%) were T790M+. Highest T790M testrate in one center was 22/28 (79%). 16/20 (80%) T790M+ pts received 3rd gen TKI for 2nd line therapy. MOS of pts receiving 3rd gen TKI (n = 31) was 51 mo vs. 25 mo for pts without 3rd gen TKI (p < 0.002).

Conclusions

In real world, a significant number of pts treated with 1st or 2nd gen TKI do not reach 2nd line therapy even with broad accessibility of 3rd gen TKI. Reasons for not receiving 2nd line therapy are in most cases deterioration of PS, death and no testing for T790M in a minority of cases. These data are important for the interpretation of the OS data of the FLAURA study as they reflect real world treatment algorithms in dedicated German lung cancer centers.

Legal entity responsible for the study

Carl v. Ossietzky University of Oldenburg, Prof. Dr. Griesinger.

Funding

Has not received any funding.

Disclosure

J. Roeper: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Roche; Honoraria (self): AstraZeneca. M. Falk: Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Boehriger Ingelheim; Honoraria (self): Roche; Honoraria (self): AstraZeneca. M. Tiemann: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: Boehriger Ingelheim; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Roche ; Honoraria (self): AstraZeneca. F. Griesinger: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Boehriger Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Celegene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Siemens; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Bayer. All other authors have declared no conflicts of interest.

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Poster Display session 1 Poster Display session

1537P - Lerociclib (G1T38), an oral CDK4/6 inhibitor, dosed continuously in combination with osimertinib for EGFRmut non-small cell lung cancer: Initial phase Ib results (ID 1613)

Presentation Number
1537P
Lecture Time
12:00 - 12:00
Speakers
  • David Berz (Beverly Hills, AL, United States of America)
Session Name
Poster Display session 1
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
12:00 - 13:00

Abstract

Background

Lerociclib (lero) is a potent, selective oral CDK4/6 inhibitor (CDK4/6i). Preclinical and early clinical data have demonstrated that lero is differentiated based on its favorable safety/tolerability profile and ability to be dosed continuously with less dose-limiting neutropenia. Encouraging preliminary efficacy has been observed in HR+/HER2- breast cancer in combination with fulvestrant (NCT#02983071). Several putative mechanisms of resistance to EGFR TKIs are upstream of the CDK4/6 pathway, and in vitro and in vivo studies with CDK4/6i + EGFR TKIs have demonstrated enhanced efficacy and delayed time to resistance. These data provide strong rationale to investigate lero + osimertinib (osi) in the clinic.

Methods

Patients with metastatic NSCLC, confirmed EGFR mutation associated with EGFR TKI sensitivity, ECOG of 0 or 1, and treatment with ≤2 lines of chemo or any EGFR TKI including osi are eligible for this phase Ib study. Patients receive lero QD or BID continuously in combination with 80 mg osi QD until disease progression. The objectives are to evaluate DLTs, safety, tolerability, PK, and anti-tumor efficacy, and to determine the dose for the randomized phase II portion of the study.

Results

Currently, 18 patients (mean age 63 years) have been enrolled and received lero doses of 200, 300, or 400 mg QD; the longest duration being 317 days. BID enrollment is ongoing. Lero is well tolerated; no lero-related SAEs have been reported, and no patient has withdrawn due to an AE. One DLT of Grade 4 neutropenia occurred at 400 mg QD. The most common lero-related TEAEs are neutropenia and diarrhea. The incidence of diarrhea with lero + osi is similar to single agent osi (FLAURA study). There have been no reports of VTE, QT prolongation, or DILI. No clinically relevant drug-drug interaction has been observed.

Conclusions

The combination of continuously administered lero + osi in patients with EGFRmut NSCLC (treatment naïve or previously treated) is well tolerated with only one DLT event to date. Updated safety, anti-tumor efficacy, and cfDNA data will be presented (NCT#03455829).

Clinical trial identification

NCT03455829.

Legal entity responsible for the study

G1 Therapeutics, Inc.

Funding

G1 Therapeutics.

Disclosure

D. Berz: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Genentech; Honoraria (self): AstraZeneca; Honoraria (self): Merck; Honoraria (self): Tempus; Honoraria (self): Biocept; Shareholder / Stockholder / Stock options, Major Owner: Valkyrie Therapeutics. A. Spira: Advisory / Consultancy: G1 Therapeutics. J.W. Goldman: Honoraria (self), Research grant / Funding (institution): AstraZeneca. Y.L. Pritchett: Full / Part-time employment: G1 Therapeutics. C.G. Cisneros: Full / Part-time employment: G1 Therapeutics. C. Li: Full / Part-time employment: G1 Therapeutics. J.A. Sorrentino: Full / Part-time employment: G1 Therapeutics. R. Malik: Full / Part-time employment: G1 Therapeutics. A.P. Beelen: Full / Part-time employment: G1 Therapeutics. All other authors have declared no conflicts of interest.

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Poster Discussion – NSCLC, metastatic Poster Discussion session

LBA85 - Longitudinal circulating tumour DNA (ctDNA) monitoring for early detection of disease progression and resistance in advanced NSCLC in FLAURA (ID 2685)

Presentation Number
LBA85
Lecture Time
17:20 - 17:20
Speakers
  • Jhanelle E. Gray (Tampa, United States of America)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45

Abstract

Background

In the phase III FLAURA study (NCT02296125), the 3rd-generation EGFR-TKI osimertinib showed superior efficacy to comparator EGFR-TKIs in previously untreated EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC). Here we report results from an exploratory analysis of ctDNA for the early detection of disease progression (PD) in FLAURA.

Methods

Treatment-naïve patients (pts) with EGFRm (ex19del/L858R) locally advanced/metastatic NSCLC (n = 556) were randomised 1:1 (osimertinib 80 mg qd: comparator [gefitinib 250 mg qd/erlotinib 150 mg qd]). Plasma samples were collected on Days 1, 8 and 15, then every 21 days for weeks (W) 3–18, then every 6W thereafter. In pts who had a plasma sample on PD and/or discontinuation, ctDNA droplet digital PCR (ddPCR; Biodesix) for EGFRm (ex19del/L858R/T790M) was performed at all available time points and C797S for post-W6 time points. C797S and T790M were the only resistance mutations assayed. ctDNA progression was defined with respect to the nadir ctDNA result and its proximity to the ddPCR detection and quantification limits.

Results

The ctDNA progression analysis included 122/556 (22%) pts with valid longitudinal monitoring ddPCR data and RECIST PD by DCO1 (12 June 2017). Across both arms, ctDNA progression preceded or co-occurred with PD in 80/122 (66%) pts with 2.7 months (mo) median lead time; 9.5 mo median progression-free survival (mPFS; n = 80). Acquired C797S or T790M was detected in 57/122 (47%) pts with ctDNA progression (osimertinib 4/50 [8%] C797S, comparator 53/72 [74%] T790M); median time to detection was 16.7 and 8.4 mo for the osimertinib and comparator arms, respectively, mirroring overall mPFS. In pts with ctDNA progression and PD (n = 106), acquired T790M and C797S were detected either at the same time as, or earlier than PD in 41/106 (38%) pts (osimertinib 2/39 [5%], comparator 39/67 [58%]); median lead time was 1.4 mo.

Conclusions

ctDNA monitoring may allow for earlier identification of pts who progress on first-line EGFR-TKI therapy and the detection of EGFR-mediated resistance mechanisms in advance of PD in EGFRm NSCLC. Future work aims to explore early detection of non-EGFR-mediated resistance.

Clinical trial identification

NCT02296125.

Editorial acknowledgement

Writing support was provided by Donna Tillotson, PhD of iMed Comms, Macclesfield, UK, an Ashfield Company, part of UDG Healthcare plc, and funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

J.E. Gray: Research grant / Funding (institution): Array; Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Takeda. N. Peled: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Takeda; Advisory / Consultancy: Eli Lilly; Honoraria (self): Foundation Medicine; Shareholder / Stockholder / Stock options: NovellusDx; Honoraria (self): Gaurdant360. A. Markovets: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. N. Nogami: Honoraria (self): Pfizer Inc.; Honoraria (self): Chugai Pharmaceutical Co. Ltd; Honoraria (self): Eli Lilly; Honoraria (self): Taiho Pharmaceutical Co. Ltd; Honoraria (self): AstraZeneca; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Ono Pharmaceutical Co. Ltd; Honoraria (self): BMS; Honoraria (self): MSD. B.C. Cho: Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bayer; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): MOGAM Institute; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Dong-A ST; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Licensing / Royalties: Champions Oncology; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Janssen; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Yuhan; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Ono; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Dizal Pharma; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (institution), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: Eli Lilly; Honoraria (institution), Advisory / Consultancy: Takeda; Shareholder / Stockholder / Stock options: TheraCanVac Inc. B. Chewaskulyong: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca. M. Majem: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer; Advisory / Consultancy: Tesaro; Speaker Bureau / Expert testimony: Hellsin; Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Speaker Bureau / Expert testimony: Amgen. K. Vishwanathan: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. A. Todd: Full / Part-time employment: AstraZeneca. Y. Rukazenkov: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Johnson: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. C. Barrett: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. J. Chmielecki: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. R. Hartmaier: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Shareholder / Stockholder / Stock options, Licensing / Royalties, Nfe2l2 exon 2 ano/or exon 3 loss from work conducted at Foundation Medicine; provisional patent filed: Foundation Medicine. S.S. Ramalingam: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy: Roche/Genentech; Honoraria (self), Advisory / Consultancy: Loxo; Honoraria (self), Advisory / Consultancy: Nektar; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Advaxis; Research grant / Funding (institution): Takeda. All other authors have declared no conflicts of interest.

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