Blood test can replace invasive biopsy for more patients with lung cancer

Barcelona, Spain, 30 September 2019 – A growing number of patients with advanced lung cancer could soon be offered a blood test to help to decide the best treatment for them instead of having to get a tumour sample for analysis. New data from the BFAST trial presented at the ESMO Congress 2019 have shown that the test can be used successfully to identify complex DNA mutations in the cells of patients with non-small cell lung cancer (NSCLC) suitable for the latest targeted medicines. (1,2) The technique detects tiny pieces of tumour DNA that are shed from cancer cells into the blood.

“One of the biggest recent changes in treatment of NSCLC has been our ability to identify targetable genetic mutations that drive progression of the disease, but it is a major challenge to get a suitable tumour sample for analysis. We showed that liquid biopsy could be used to detect a complex type of driver mutation, called ALK, in patients with NSCLC. These then responded at least as well to targeted therapy as in previous studies using conventional biopsy techniques,” explained study author Dr Shirish Gadgeel, Rogel Cancer Center, University of Michigan, USA.

In the BFAST analysis, over 2,000 patients with untreated NSCLC had blood tests using state-of-the-art technology to check for multiple driver genetic mutations. (2) Approximately 1 in 20 were found to have tumour DNA showing a rearrangement in the ALK gene. In patients treated with alectinib, a cancer treatment that targets the ALK mutation, over three quarters showed no signs of disease progression in the subsequent 12 months.

“Liquid biopsy identified a similar proportion of patients with ALK mutations to that typically seen with traditional biopsy and the results with alectinib compared well with those seen in a pivotal study of this treatment,” said Gadgeel.

Commenting on the results of the study, Prof Alberto Bardelli, Department of Oncology, University of Turin, Italy, said: “Rearrangement in the ALK gene described in the BFAST study is typically difficult to detect so it is an important advance to have shown that it can be detected in the blood and used to guide ALK inhibitor treatment which has then been demonstrated to be effective in patients with this mutation.”

“It is encouraging to see that increasing numbers of patients with lung cancer can benefit from liquid biopsy to identify their disease mutation instead of tissue samples. At present the technology is quite expensive but as it becomes more widely used, the cost is likely to come down so that testing becomes more affordable and available in daily practice,” he added.

Study results

In the Phase II/III BFAST trial, 2,219 patients with stage IIIB/IV untreated NSCLC had blood-based next generation sequencing (NGS) of actionable genetic alterations and results were obtained in 2,188 patients. Overall, 119 patients (5.4%) had ALK+ disease and 87 of these were enrolled to receive alectinib. Median follow-up was 12.6 months. Confirmed objective response rate (ORR) reported by investigators was 87.4% (95% CI 78.5-93.5) and 12-month duration of response (DoR) was 75.9% (95% CI 63.6-88.2). Median progression-free survival (PFS) was not reached but 12-month PFS reported by investigators was 78.4% (95% CI 69.1-87.7). Safety data were consistent with the known safety profile of alectinib.

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Notes to Editors

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References

1 https://www.esmo.org/Conferences/ESMO-Congress-2019

2 LBA81_PR ‘Phase II/III blood first assay screening trial (BFAST) in patients (pts) with treatment-naive NSCLC: initial results from ALK+ cohort’ will be presented by Shirish Gadgeel during the proffered paper session on Monday, 30 September 2019, 08:30-10:00 CEST in Madrid Auditorium (Hall 2). Annals of Oncology, Volume 30, Supplement 5, October 2019

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LBA81_PR – Phase II/III blood-first assay screening trial (BFAST) in treatment-naive NSCLC: initial results from the ALK+ cohort

S.M. Gadgeel¹, T.S.K. Mok², S. Peters³, J.A.A. Alexander⁴, N.B. Leighl⁵, V. Sriuranpong⁶, M. Perol⁷, G. De Castro Jr.⁸, E. Nadal⁹, F. De Marinis¹⁰, J.-Y. Han¹¹, M. Yan¹², T. Riehl¹³, E. Schleifman¹³, S.M. Paul¹³, S. Mocci¹³, D. Shames¹³, M.S. Mathisen¹³, R. Dziadziuszko¹⁴

¹Medical Oncology Department, Rogel Cancer Center; University of Michigan, Ann Arbor, United States of America, ²State Key Laboratory Of South China, The Chinese University of Hong Kong, Hong Kong, China, ³Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois – CHUV, Lausanne, Switzerland, ⁴Clinica De Oncologia Toracica, Health Pharma Professional Research, New Mexico, Mexico, ⁵Cancer Clinical Research Unit (ccru), Princess Margaret Cancer Centre, Toronto, Canada, ⁶Medical Oncology Unit, King Chulalongkorn Memorial Hospital, Bangkok, Thailand, ⁷Centre Leon Berard, Lyon, France, ⁸Clinical Oncology, Instituto do Cancer do Estado de Sao Paulo, Sao Paulo, Brazil, ⁹Oncology, Institut Catala d’Oncologia (ICO), Barcelona, Spain, ¹⁰Irccs, European Institute of Oncology, Milan, Italy, ¹¹Medical Oncology, National Cancer Center, Goyang, Korea, Republic of, ¹²Medical Oncology, F. Hoffmann-La Roche, Mississauga, Canada, ¹³Product Development Oncology, Genentech Inc.,South San Francisco, United States of America, ¹⁴Department Of Oncology And Radiotherapy, Medical University of Gdansk, Gdansk, Poland

Background: Tissue-based assessment of actionable mutations in pts with NSCLC is limited by invasive biopsies and adequacy of biopsied tumour material. Blood-based testing may overcome such limitations, allowing multiplex profiling in a single test. BFAST (NCT03178552) is an ongoing multicentre, open-label, multi-cohort study evaluating the relationship between blood-based next-generation sequencing (NGS) detection of actionable genetic alterations in cell-free DNA, and the activity of targeted therapies and immunotherapy in pts with treatment-naive advanced NSCLC. We present first results from the ALK+ cohort.

Methods: Pts greater than equal to 18 years with stage IIIB/IV ALK+ NSCLC (detected by blood-based NGS) received oral alectinib 600mg twice daily. Asymptomatic/treated central nervous system (CNS) metastases were permitted. All pts (with/without CNS disease) had 8-weekly restaging and brain scans. Primary endpoint: confirmed investigator (INV)-assessed objective response rate (ORR; RECIST v1.1). Key secondary endpoints: independent review facility (IRF)-assessed ORR; INV- and IRF-assessed duration of response (DoR), progression-free survival (PFS), overall survival; and safety.

Results: Of 2,219 pts screened, blood-based NGS yielded results in 2,188 pts. Overall, 119 pts (5.4%) had ALK+ disease; 87 pts were enrolled and received alectinib. EML4 was the fusion partner in 73 (84%) pts, with TP53 mutations detected in 38 (44%) pts. Median blood-based tumour mutational burden was 2 (range, 0-21). Median follow-up: 12.6 months (range, 2.6-18.7). Confirmed ORR: 87.4% (95% CI 78.5-93.5) by INV and 92.0% (95% CI 84.1-96.7) by IRF. The 12-month INV-confirmed DoR was 75.9% (95% CI 63.6-88.2). In 35 (40%) pts with asymptomatic baseline CNS disease, ORR by INV was 91.4% (95% CI 76.9-98.2). Median PFS: not reached; 12-month PFS by INV was 78.4% (95% CI 69.1-87.7). Safety data were consistent with the known safety profile of alectinib.

Conclusions: Blood-based detection of ALK fusions results in high ORR and clinical benefit in pts receiving alectinib. These data validate the clinical utility of blood-based NGS as an additional method to inform clinical decision-making in ALK+ NSCLC.

Clinical trial identification: NCT03178552

Editorial acknowledgement: Medical Writing support was provided by Nicola Griffin of Gardiner-Caldwell Communications and was funded by F. Hoffmann-La Roche.

Legal entity responsible for the study: F. Hoffmann-La Roche Ltd.

Funding: F. Hoffman-La Roche Ltd.

Disclosure: S.M. Gadgeel: Honoraria (self), Advisory / Consultancy: Ariad, AstraZeneca, Bristol-Myers Squibb, Pfizer and F. Hoffmann-La Roche Ltd/Genentech.

T.S.K. Mok: Leadership role: Sanonics Ltd; Honoraria (self), Advisory / Consultancy: ACEA Biosciences, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Chimed, Cirina, Fishawack Facilitate, Ignyta, Janssen, Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, OncoGenex, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, SFJ Pharm; Research grant / Funding (self): AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Merck Sharp & Dohme, Novartis, Pfizer, F. Hoffmann-La Roche Ltd, SFJ Pharmaceutical and XCovery.

S. Peters: Honoraria (self), Advisory / Consultancy: Abbvie, Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Clovis, Eli Lilly, F. Hoffmann-La Roche Ltd, Janssen, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Regeneron and Takeda; Speaker Bureau / Expert testimony: AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, F. Hoffmann-La Roche Ltd, Merck Sharp & Dohme, Novartis and Pfizer.

J.A.A. Alexander: Honoraria (self), Advisory / Consultancy: AstraZeneca, Boehringer-Ingelheim Bristol-Myers Squibb, Pfizer and F. Hoffmann-La Roche Ltd/Genentech, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Takeda.

N.B. Leighl: Research grant / Funding (self): F. Hoffmann-La Roche, Array, Guardant and AstraZeneca; Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, F. Hoffmann-Lar Roche, Pfizer ; Advisory / Consultancy: Excovery.

V. Sriuranpong: Honoraria (self), Advisory / Consultancy: AstraZeneca, Novartis, F. Hoffmann-La Roche Ltd, Pfizer, Sanofi, Eisai, Boehringer, Taiho, Merck Sharp & Dohme, Bristol-Myers Squibb ; Research grant / Funding (institution): AstraZeneca, Novartis, F. Hoffmann-La Roche Ltd, Pfizer, Boehringer, Eisai, Taiho, Lilly and Merck Sharp & Dohme.

M. Perol: Honoraria (self): F. Hoffmann-La Roche Ltd, AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Takeda, Chugai, Boehringer-Ingelheim, Eli Lilly, Amgen and Abbvie.

G. De Castro Jr.: Advisory / Consultancy: AstraZeneca, Merck Sharp & Dohme, Bristol-Myers Squibb, F. Hoffmann-La Roche Ltd, Novartis, Boehringer-Ingelheim, Pfizer, Bayer; Speaker Bureau / Expert testimony: Merck Sharp & Dohme, Bristol-Myers Squibb, Novartis, AstraZeneca, Pfizer, F. Hoffmann-La Roche Ltd, Bayer, TEVA ; Travel / Accommodation / Expenses: Merck Sharp & Dohme, Bristol-Myers Squibb, F. Hoffmann-La Roche Ltd, Bayer, Novartis, Boehringer-Ingelheim, AstraZeneca, Pfizer and Bayer..

E. Nadal: Honoraria (self), Advisory / Consultancy: AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, F. Hoffmann-La Roche Ltd, Janssen, Merck Sharp & Dohme, Pfizer and Takeda.

F. De Marinis: Honoraria (self): F. Hoffmann La Roche Ltd, Bristol-Myers Squibb, AstraZeneca and Merck.

J. Han: Honoraria (self): Roche, AstraZeneca, BMS, MSD, Takeda; Advisory / Consultancy: AstraZeneca, BMS, MSD, Lilly, Novartis, Pfizer, Takeda; Research grant / Funding (self): Roche, Pfizer, ONO .

M. Yan: Full / Part-time employment: F. Hoffmann-La Roche Ltd..

T. Riehl: Full / Part-time employment: Genentech, Inc.

E. Schleifman: Full / Part-time employment: Genentech, Inc.

S.M. Paul: Full / Part-time employment: Genentech, Inc.

S. Mocci: Full / Part-time employment: Genentech, Inc.

D. Shames: Full / Part-time employment: Genentech, Inc.

M.S. Mathisen: Full / Part-time employment: Genentech, Inc.

R. Dziadziuszko: Honoraria (self), Advisory / Consultancy: F. Hoffmann-La Roche Ltd, Pfizer, Boehringer-Ingelheim, Clovis Oncology, Novartis, AstraZeneca and Tesaro.