- Email: [email protected]
PIK3CA alterations in metastatic breast cancer (mBC)
Annals of Oncology 30 (Supplement 5): v104–v142, 2019 doi:10.1093/annonc/mdz242
BREAST CANCER, METASTATIC 305O
L.A. Emens1, F.J. Esteva2, M. Beresford3, C. Saura4, M. De Laurentiis5, S-B. Kim6, S-A. Im7, Y. Wang8, A. Mani9, J. Shah9, H. Liu9, S. de Haas10, M. Patre11, S. Loi12 1 Medicine/Haematology-Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, USA, 2 Medical Oncology, Perlmutter Cancer Center at NYU Langone Medical Center, New York, NY, USA, 3Oncology and Haematology, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK, 4Medicine and Surgery, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, 5Surgical Oncology, IRCCS Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy, 6Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 7Internal Medicine, SNUH-Seoul National University Hospital, Seoul, Republic of Korea, 8Product Development, Roche (China) Holding Ltd, Shanghai, China, 9Product Development Oncology, Genentech, Inc., South San Francisco, CA, USA, 10Oncology Biomarker Development, F. Hoffmann-La Roche, Basel, Switzerland, 11Product Development Oncology, F. Hoffmann-La Roche, Basel, Switzerland, 12Translational Breast Cancer Genomics Lab, Division of Research, Peter MacCallum Cancer Center, Melbourne, VIC, Australia Background: T-DM1 is indicated for the treatment of HER2þ metastatic BC previously treated with trastuzumab and a taxane, separately or in combination. Atezo is an anti-PD-L1 antibody that inhibits PD-L1 binding to PD-1 and B7.1 thereby restoring antitumor immunity. In a phase 3 study, the addition of atezo to nab-paclitaxel significantly improved PFS in PD-L1þ pts with metastatic triple negative BC. In KATE2 (NCT02924883), adding atezo to T-DM1 in pts with HER2þ BC did not significantly increase PFS compared to T-DM1þpbo in the ITT population, but PFS was numerically longer in PD-L1þ pts. Here, we present OS and updated safety data from KATE2. Methods: Pts with advanced HER2-positive BC that had progressed after treatment with trastuzumab and a taxane were randomized 2:1 to atezo 1200 mg or pbo, þ TDM1 3.6 mg/kg IV q3w. Pts were grouped by tumor infiltrating PD-L1þ immune cell (IC) status: IC0 vs IC1/2/3 (<1% vs 1%, respectively) using VENTANA SP142. The preplanned OS analysis in the ITT population was a secondary endpoint with 30% power to detect an effect. OS in PD-L1 subgroups was analyzed post-hoc. Results: As of the cutoff date (11 Dec 2018), median follow-up was 19.5 mo in the atezoþT-DM1 arm and 18.2 mo in the pboþT-DM1 arm. With 52 OS events reported, median OS was not reached in either arm. In the ITT population, 1-year OS was similar in both arms. In the PD-L1þ subgroup, 1-year OS was greater in the atezoþT-DM1 arm. The safety profile was consistent with the known safety profile of each drug. Grade 3 AEs (52.6% vs 44.8%) and serious AEs (36.1% vs 20.9%)—primarily pyrexia— were more frequent in the atezoþT-DM1 arm than in the T-DM1þpbo arm. Conclusions: These data suggest a possible OS benefit with atezoþT-DM1 in PD-L1þ pts. However, given the small number of OS events, the short follow-up and lack of statistical power, further study is necessary.
Table: 305O
Editorial acknowledgement: Medical writing assistance was provided by Katherine Stevens-Favorite, PhD and Holly Strausbaugh, PhD of Twist Medical LCC and funded by F. Hoffmann-La Roche. Legal entity responsible for the study: F. Hoffmann - La Roche. Funding: F. Hoffmann - La Roche. Disclosure: L.A. Emens: Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol Meyers Squibb; Honoraria (self), Advisory / Consultancy: Celgene; Advisory / Consultancy: eTHeRNA; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy: Gristone; Honoraria (self), Advisory / Consultancy: Medimmune; Advisory / Consultancy: Molecuvax; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Macrogenics; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy: Peregrine; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Replimune; Honoraria (self), Advisory / Consultancy: Syndax; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Vaccinex; Research grant / Funding (institution): Aduro; Research grant / Funding (institution), Same dislosure for Corvus, Dept of Defense, EMD Serono, HeritX Inc, Maxcyte, Merck: Breast Cancer Research Foundation; Research grant / Funding (institution), Licensing / Royalties, IND Licensing vaccine <25k: Aduro. F.J. Esteva: Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Novartis. C. Saura: Research grant / Funding (institution): Roche-Genentech; Research grant / Funding (institution): Macrogenics; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Piqur therapeutics; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Puma biotechnology; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Synthon biopharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Travel / Accommodation / Expenses: Daiichi Sankyo; Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy, Travel / Accommodation / Expenses: Genomyc Health; Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre. M. De Laurentiis: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. S. Kim: Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Sanofi-Genzyme; Research grant / Funding (institution): Dongkook Inc. S. Im: Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy: Amgen; Advisory / Consultancy: Eisai; Advisory / Consultancy: Roche; Advisory / Consultancy: Hanmi; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): Novartis. Y. Wang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche (China) Holding Ltd. A. Mani: Full / Part-time employment: Roche/Genentech; Shareholder / Stockholder / Stock options: Roche/Genentech. J. Shah: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech. H. Liu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. S. de Haas: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. M. Patre: Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment, Methods of treating her2 - positive metastatic breast cancer A61K47/6855: F. Hoffman-La Roche. S. Loi: Research grant / Funding (institution), Non-remunerated activity/ies: Novartis; Research grant / Funding (institution), Non-remunerated activity/ies: Bristol Meyers Squibb; Research grant / Funding (institution), Non-remunerated activity/ies: Roche-Genentech; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution), Non-remunerated activity/ies: Pfizer; Non-remunerated activity/ies: Seattle Genentics; Non-remunerated activity/ies: Merck; Research grant / Funding (institution): Eli Lilly. All other authors have declared no conflicts of interest.
306PD
PIK3CA alterations in metastatic breast cancer (mBC) 1
J. Albanell , D. Casadevall1, E.S. Sokol2, L.A. Albacker3, J.A. Elvin4, J-A. Vergilio4, J.K. Killian4, N. Ngo4, D. Lin4, S. Ramkissoon4, E. Severson4, S.M. Ali2, A.B. Schrock5, J. Chung2, P. Reddy6, V.A. Miller2, B.M. Alexander2, K. McGregor6, J.S. Ross7, B. LeylandJones8 1 Oncology, University Hospital del Mar, Barcelona, Spain, 2Clinical Development, Foundation Medicine, Cambridge, MA, USA, 3Cancer Genomics, Foundation Medicine, Cambridge, MA, USA, 4Pathology, Foundation Medicine, Cambridge, MA, USA, 5Clinical Development, Foundation Medicine, Cambridge, MI, USA, 6Medical Affairs, Foundation Medicine, Cambridge, MA, USA, 7Pathology and Urology, Upstate Medical University, Syracuse, NY, USA, 8Medical Oncology, Avera Cancer Institute, Sioux Falls, SD, USA Background: The anticipated approval of the first specific PIK3CA inhibitor, apelisib, has increased interest in the frequency and range of PIK3CA genomic alterations (GA) in the major subtypes of mBC.
C European Society for Medical Oncology 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V
All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz242.001/5576837 by guest on 26 October 2019
Overall survival (OS) in KATE2, a phase II study of programmed death ligand 1 (PD-L1) inhibitor atezolizumab (atezo)1trastuzumab emtansine (T-DM1) vs placebo (pbo)1T-DM1 in previously treated HER21 advanced breast cancer (BC)
abstracts
Annals of Oncology
Table: 306PD ERþ/HER2- (1,249)
AR amp MSI High CD274 (PD-L1) amp TMB > 10/20 mut/Mb PD-L1 TILs low/high
TNBC (925)
PIK3CAmutþ 481 (39%) CN 4% Mut 96% H1047R 30% E545K 17% E542K 15% N345K 5%
PIK3CAmut768 (61%)
PIK3CAmutþ 715 (37%) CN 8% Mut 92% H1047R 34% E545K 15% E542K 10% N345K 3%
PIK3CAmut1,207 (63%)
PIK3CAmutþ 192 (21%) CN 17% Mut 83% H1047R 30% E545K 8% E542K 7% N345K 3%
PIK3CAmut733 (79%)
57 (23-89þ) 100% 39% 9% 11% 16% 1%/3% 0% 2% FGFR1 14% EGFR 1% BRAF 1% <1% <1% <1% 11%/5% 9%/0% n ¼ 33
53 (22-89) 0% 47% 12% 5% 16% 4%/7% 0% 3% FGFR1 21% EGFR 2% BRAF 2% <1% <1% 1% 5%/1% 11%/0% n ¼ 57
55 (25-88) 100% 75% 3% 5% 7% 1%/2% 100% 7% FGFR1 11% EGFR 3% BRAF 1% 2% <1% 1% 11%/3% 11%/0% n ¼ 45
53 (20-89þ) 0% 68% 6% 3% 6% 3%/3% 100% 6% FGFR1 11% EGFR 3% BRAF 1% 1% <1% 1% 8%/1% 9%/0% n ¼ 79
56.5 (30-89þ) 100% 74% 15% 9% 2% 3%/3% 0% 5% FGFR1 9% EGFR 11% BRAF 3% 3% 0% 3% 11%/3% 20%/0% n ¼ 15
53 (20-89þ) 0% 88% 15% 3% <1% 8%/4% 0% 2% FGFR1 8% EGFR 3% BRAF 3% <1% <1% 3% 6%/1% 17%/1% n ¼ 75
Methods: DNA was extracted from 3,871 mBC: 1,259 ERþ/HER2-, 1,969 HER2 amplified (amp) and 643 TNBC. GA, tumor mutational burden (TMB) and microsatellite instability (MSI) were identified by hybrid-capture. PD-L1 was determined by IHC. Results: PIK3CA GA were significantly higher in ER þ (39%) and HER2amp (37%) and lower in TNBC (21%) groups and dominated by point mutations and indels (mut) (Table). The H1047R was the most frequent PIK3CA GA in all groups. ESR1 GA were highest in ERþ and BRCA1 GA were most frequent in PIK3CAmut- TNBC and BRCA2 GA were most frequent in PIK3CAmut- ERþ. FGFR1 GA were significantly more frequent in PIK3CAmut- ERþ and EGFR and BRAF GA were most frequent in PIK3CAmutþ TNBC. Biomarkers of potential immunotherapy benefit including CD274amp and PD-L1 expression in immunocytes were most frequent in the TNBC patients, while TMB was highest in the PIK3CAmutþ cohort, regardless of subtype. Conclusions: A wide variety of PIK3CA GA are identified in mBC and appear to influence other important biomarkers such as BRCA1/2 GA and TMB status. The PIK3CA GA distribute differently among the ERþ, HER2þ and TNBC cohorts and may impact the initial and future use of PIK3CA inhibitors in the treatment of the disease. Legal entity responsible for the study: Foundation Medicine. Funding: Foundation Medicine. Disclosure: E.S. Sokol: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. L.A. Albacker: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J.A. Elvin: Shareholder / Stockholder / Stock options, Full / Parttime employment: Foundation Medicine. J. Vergilio: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J..K. Killian: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. N. Ngo: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. D. Lin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. S. Ramkissoon: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. E. Severson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. S.M. Ali: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. A.B. Schrock: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J. Chung: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. P. Reddy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. V.A. Miller: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. B.M. Alexander: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Foundation Medicine. K. McGregor: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J.S. Ross: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. All other authors have declared no conflicts of interest.
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz242 | v105
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz242.001/5576837 by guest on 26 October 2019
Age (range in years) PIK3CA GA TP53 GA PTEN GA CDH1 GA ESR1 GA BRCA1/2 GA HER2 amp HER2 mut Other Kinase GA
HER2 Amp (1,922)
BREAST CANCER, METASTATIC 305O
L.A. Emens1, F.J. Esteva2, M. Beresford3, C. Saura4, M. De Laurentiis5, S-B. Kim6, S-A. Im7, Y. Wang8, A. Mani9, J. Shah9, H. Liu9, S. de Haas10, M. Patre11, S. Loi12 1 Medicine/Haematology-Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, USA, 2 Medical Oncology, Perlmutter Cancer Center at NYU Langone Medical Center, New York, NY, USA, 3Oncology and Haematology, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK, 4Medicine and Surgery, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, 5Surgical Oncology, IRCCS Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy, 6Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 7Internal Medicine, SNUH-Seoul National University Hospital, Seoul, Republic of Korea, 8Product Development, Roche (China) Holding Ltd, Shanghai, China, 9Product Development Oncology, Genentech, Inc., South San Francisco, CA, USA, 10Oncology Biomarker Development, F. Hoffmann-La Roche, Basel, Switzerland, 11Product Development Oncology, F. Hoffmann-La Roche, Basel, Switzerland, 12Translational Breast Cancer Genomics Lab, Division of Research, Peter MacCallum Cancer Center, Melbourne, VIC, Australia Background: T-DM1 is indicated for the treatment of HER2þ metastatic BC previously treated with trastuzumab and a taxane, separately or in combination. Atezo is an anti-PD-L1 antibody that inhibits PD-L1 binding to PD-1 and B7.1 thereby restoring antitumor immunity. In a phase 3 study, the addition of atezo to nab-paclitaxel significantly improved PFS in PD-L1þ pts with metastatic triple negative BC. In KATE2 (NCT02924883), adding atezo to T-DM1 in pts with HER2þ BC did not significantly increase PFS compared to T-DM1þpbo in the ITT population, but PFS was numerically longer in PD-L1þ pts. Here, we present OS and updated safety data from KATE2. Methods: Pts with advanced HER2-positive BC that had progressed after treatment with trastuzumab and a taxane were randomized 2:1 to atezo 1200 mg or pbo, þ TDM1 3.6 mg/kg IV q3w. Pts were grouped by tumor infiltrating PD-L1þ immune cell (IC) status: IC0 vs IC1/2/3 (<1% vs 1%, respectively) using VENTANA SP142. The preplanned OS analysis in the ITT population was a secondary endpoint with 30% power to detect an effect. OS in PD-L1 subgroups was analyzed post-hoc. Results: As of the cutoff date (11 Dec 2018), median follow-up was 19.5 mo in the atezoþT-DM1 arm and 18.2 mo in the pboþT-DM1 arm. With 52 OS events reported, median OS was not reached in either arm. In the ITT population, 1-year OS was similar in both arms. In the PD-L1þ subgroup, 1-year OS was greater in the atezoþT-DM1 arm. The safety profile was consistent with the known safety profile of each drug. Grade 3 AEs (52.6% vs 44.8%) and serious AEs (36.1% vs 20.9%)—primarily pyrexia— were more frequent in the atezoþT-DM1 arm than in the T-DM1þpbo arm. Conclusions: These data suggest a possible OS benefit with atezoþT-DM1 in PD-L1þ pts. However, given the small number of OS events, the short follow-up and lack of statistical power, further study is necessary.
Table: 305O
Editorial acknowledgement: Medical writing assistance was provided by Katherine Stevens-Favorite, PhD and Holly Strausbaugh, PhD of Twist Medical LCC and funded by F. Hoffmann-La Roche. Legal entity responsible for the study: F. Hoffmann - La Roche. Funding: F. Hoffmann - La Roche. Disclosure: L.A. Emens: Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol Meyers Squibb; Honoraria (self), Advisory / Consultancy: Celgene; Advisory / Consultancy: eTHeRNA; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy: Gristone; Honoraria (self), Advisory / Consultancy: Medimmune; Advisory / Consultancy: Molecuvax; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Macrogenics; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy: Peregrine; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Replimune; Honoraria (self), Advisory / Consultancy: Syndax; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Vaccinex; Research grant / Funding (institution): Aduro; Research grant / Funding (institution), Same dislosure for Corvus, Dept of Defense, EMD Serono, HeritX Inc, Maxcyte, Merck: Breast Cancer Research Foundation; Research grant / Funding (institution), Licensing / Royalties, IND Licensing vaccine <25k: Aduro. F.J. Esteva: Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Novartis. C. Saura: Research grant / Funding (institution): Roche-Genentech; Research grant / Funding (institution): Macrogenics; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Piqur therapeutics; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Puma biotechnology; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Synthon biopharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Travel / Accommodation / Expenses: Daiichi Sankyo; Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy, Travel / Accommodation / Expenses: Genomyc Health; Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre. M. De Laurentiis: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. S. Kim: Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Sanofi-Genzyme; Research grant / Funding (institution): Dongkook Inc. S. Im: Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy: Amgen; Advisory / Consultancy: Eisai; Advisory / Consultancy: Roche; Advisory / Consultancy: Hanmi; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): Novartis. Y. Wang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche (China) Holding Ltd. A. Mani: Full / Part-time employment: Roche/Genentech; Shareholder / Stockholder / Stock options: Roche/Genentech. J. Shah: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech. H. Liu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. S. de Haas: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. M. Patre: Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment, Methods of treating her2 - positive metastatic breast cancer A61K47/6855: F. Hoffman-La Roche. S. Loi: Research grant / Funding (institution), Non-remunerated activity/ies: Novartis; Research grant / Funding (institution), Non-remunerated activity/ies: Bristol Meyers Squibb; Research grant / Funding (institution), Non-remunerated activity/ies: Roche-Genentech; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution), Non-remunerated activity/ies: Pfizer; Non-remunerated activity/ies: Seattle Genentics; Non-remunerated activity/ies: Merck; Research grant / Funding (institution): Eli Lilly. All other authors have declared no conflicts of interest.
306PD
PIK3CA alterations in metastatic breast cancer (mBC) 1
J. Albanell , D. Casadevall1, E.S. Sokol2, L.A. Albacker3, J.A. Elvin4, J-A. Vergilio4, J.K. Killian4, N. Ngo4, D. Lin4, S. Ramkissoon4, E. Severson4, S.M. Ali2, A.B. Schrock5, J. Chung2, P. Reddy6, V.A. Miller2, B.M. Alexander2, K. McGregor6, J.S. Ross7, B. LeylandJones8 1 Oncology, University Hospital del Mar, Barcelona, Spain, 2Clinical Development, Foundation Medicine, Cambridge, MA, USA, 3Cancer Genomics, Foundation Medicine, Cambridge, MA, USA, 4Pathology, Foundation Medicine, Cambridge, MA, USA, 5Clinical Development, Foundation Medicine, Cambridge, MI, USA, 6Medical Affairs, Foundation Medicine, Cambridge, MA, USA, 7Pathology and Urology, Upstate Medical University, Syracuse, NY, USA, 8Medical Oncology, Avera Cancer Institute, Sioux Falls, SD, USA Background: The anticipated approval of the first specific PIK3CA inhibitor, apelisib, has increased interest in the frequency and range of PIK3CA genomic alterations (GA) in the major subtypes of mBC.
C European Society for Medical Oncology 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V
All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz242.001/5576837 by guest on 26 October 2019
Overall survival (OS) in KATE2, a phase II study of programmed death ligand 1 (PD-L1) inhibitor atezolizumab (atezo)1trastuzumab emtansine (T-DM1) vs placebo (pbo)1T-DM1 in previously treated HER21 advanced breast cancer (BC)
abstracts
Annals of Oncology
Table: 306PD ERþ/HER2- (1,249)
AR amp MSI High CD274 (PD-L1) amp TMB > 10/20 mut/Mb PD-L1 TILs low/high
TNBC (925)
PIK3CAmutþ 481 (39%) CN 4% Mut 96% H1047R 30% E545K 17% E542K 15% N345K 5%
PIK3CAmut768 (61%)
PIK3CAmutþ 715 (37%) CN 8% Mut 92% H1047R 34% E545K 15% E542K 10% N345K 3%
PIK3CAmut1,207 (63%)
PIK3CAmutþ 192 (21%) CN 17% Mut 83% H1047R 30% E545K 8% E542K 7% N345K 3%
PIK3CAmut733 (79%)
57 (23-89þ) 100% 39% 9% 11% 16% 1%/3% 0% 2% FGFR1 14% EGFR 1% BRAF 1% <1% <1% <1% 11%/5% 9%/0% n ¼ 33
53 (22-89) 0% 47% 12% 5% 16% 4%/7% 0% 3% FGFR1 21% EGFR 2% BRAF 2% <1% <1% 1% 5%/1% 11%/0% n ¼ 57
55 (25-88) 100% 75% 3% 5% 7% 1%/2% 100% 7% FGFR1 11% EGFR 3% BRAF 1% 2% <1% 1% 11%/3% 11%/0% n ¼ 45
53 (20-89þ) 0% 68% 6% 3% 6% 3%/3% 100% 6% FGFR1 11% EGFR 3% BRAF 1% 1% <1% 1% 8%/1% 9%/0% n ¼ 79
56.5 (30-89þ) 100% 74% 15% 9% 2% 3%/3% 0% 5% FGFR1 9% EGFR 11% BRAF 3% 3% 0% 3% 11%/3% 20%/0% n ¼ 15
53 (20-89þ) 0% 88% 15% 3% <1% 8%/4% 0% 2% FGFR1 8% EGFR 3% BRAF 3% <1% <1% 3% 6%/1% 17%/1% n ¼ 75
Methods: DNA was extracted from 3,871 mBC: 1,259 ERþ/HER2-, 1,969 HER2 amplified (amp) and 643 TNBC. GA, tumor mutational burden (TMB) and microsatellite instability (MSI) were identified by hybrid-capture. PD-L1 was determined by IHC. Results: PIK3CA GA were significantly higher in ER þ (39%) and HER2amp (37%) and lower in TNBC (21%) groups and dominated by point mutations and indels (mut) (Table). The H1047R was the most frequent PIK3CA GA in all groups. ESR1 GA were highest in ERþ and BRCA1 GA were most frequent in PIK3CAmut- TNBC and BRCA2 GA were most frequent in PIK3CAmut- ERþ. FGFR1 GA were significantly more frequent in PIK3CAmut- ERþ and EGFR and BRAF GA were most frequent in PIK3CAmutþ TNBC. Biomarkers of potential immunotherapy benefit including CD274amp and PD-L1 expression in immunocytes were most frequent in the TNBC patients, while TMB was highest in the PIK3CAmutþ cohort, regardless of subtype. Conclusions: A wide variety of PIK3CA GA are identified in mBC and appear to influence other important biomarkers such as BRCA1/2 GA and TMB status. The PIK3CA GA distribute differently among the ERþ, HER2þ and TNBC cohorts and may impact the initial and future use of PIK3CA inhibitors in the treatment of the disease. Legal entity responsible for the study: Foundation Medicine. Funding: Foundation Medicine. Disclosure: E.S. Sokol: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. L.A. Albacker: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J.A. Elvin: Shareholder / Stockholder / Stock options, Full / Parttime employment: Foundation Medicine. J. Vergilio: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J..K. Killian: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. N. Ngo: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. D. Lin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. S. Ramkissoon: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. E. Severson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. S.M. Ali: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. A.B. Schrock: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J. Chung: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. P. Reddy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. V.A. Miller: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. B.M. Alexander: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Foundation Medicine. K. McGregor: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J.S. Ross: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. All other authors have declared no conflicts of interest.
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz242 | v105
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz242.001/5576837 by guest on 26 October 2019
Age (range in years) PIK3CA GA TP53 GA PTEN GA CDH1 GA ESR1 GA BRCA1/2 GA HER2 amp HER2 mut Other Kinase GA
HER2 Amp (1,922)