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Mini Oral - Breast cancer, metastatic

283MO - Ipatasertib (IPAT) + paclitaxel (PAC) for PIK3CA/AKT1/PTEN-altered hormone receptor-positive (HR+) HER2-negative advanced breast cancer (aBC): Primary results from Cohort B of the IPATunity130 randomised phase III trial

Date

18 Sep 2020

Session

Mini Oral - Breast cancer, metastatic

Presenters

Nicholas Turner

Citation

Annals of Oncology (2020) 31 (suppl_4): S348-S395. 10.1016/annonc/annonc268

Authors

N. Turner1, R. Dent2, J. O'Shaughnessy3, S. Kim4, S. Isakoff5, C.H. Barrios6, S. Saji7, I. Bondarenko8, Z. Nowecki9, Q. Lian10, S. Reilly11, H. Hinton12, M. Wongchenko13, A. Mani14, M. Oliveira15

Author affiliations

  • 1 Breast Unit, The Royal Marsden NHS Foundation Trust; and Breast Cancer Now Research Centre, The Institute of Cancer Research, SW3 6JJ - London/GB
  • 2 Division Of Medical Oncology, National Cancer Centre Singapore, 169610 - Singapore/SG
  • 3 Medical Oncology, Baylor University Medical Center, Texas Oncology, US Oncology, 75246 - Dallas/US
  • 4 Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR
  • 5 Division Of Hematology And Oncology, Massachusetts General Hospital, 02114 - Boston/US
  • 6 Medical Oncology, Latin American Cooperative Oncology Group, 90610-000 - Porto Alegre/BR
  • 7 Department Of Medical Oncology, Fukushima Medical University Hospital, 960-1295 - Fukushima City/JP
  • 8 Oncology And Medical Radiology Department, City Clinical Hospital No. 4, Dnipropetrovsk/UA
  • 9 Oncology Centre, Instytut im. Marii-Sklodowskiej, 02-781 - Warsaw/PL
  • 10 Biostatistics, Genentech, Inc., South San Francisco/US
  • 11 Pharma Development, Roche Products Ltd, AL7 1TW - Welwyn Garden City/GB
  • 12 Product Development Safety, F. Hoffmann-La Roche Ltd, 4070 - Basel/CH
  • 13 Oncology Biomarker Development, Genentech, Inc., 94080 - South San Francisco/US
  • 14 Product Development Oncology, Genentech, Inc., 94080 - South San Francisco/US
  • 15 Medical Oncology Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona/ES
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Resources

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Abstract 283MO

Background

PI3K/AKT pathway alterations occur in ∼50% of HR+ breast cancers. In a phase II trial in triple-negative aBC, adding IPAT to PAC improved progression-free survival (PFS), especially in patients (pts) with PIK3CA/AKT1/PTEN-altered tumours [Kim 2017].

Methods

IPATunity130 Cohort B enrolled pts with HR+ HER2– PIK3CA/AKT1/PTEN-altered measurable aBC suitable for chemotherapy (CT). Pts with prior CT for aBC or relapse <1 y since (neo)adjuvant CT were ineligible. Pts were randomised 2:1 to IPAT (400 mg d1–21) + PAC (80 mg/m2 d1, 8 & 15) on a 28 d cycle or placebo (PBO) + PAC until progression or unacceptable toxicity, stratified by (neo)adjuvant CT, prior PI3K/mTOR inhibitor and region. The primary endpoint was investigator-assessed PFS.

Results

146 pts were randomised to IPAT + PAC and 76 to PBO + PAC. Prior therapy was balanced between arms, with (neo)adjuvant CT in 55%, endocrine therapy for aBC in 46%, PI3K/mTOR inhibitor in 24% and CDK4/6 inhibitor in 26%. At data cut-off (17/1/20; median follow-up 12.9 mo) 21% of pts remained on therapy. Median investigator-assessed PFS was 9.3 mo in both arms (HR 1.00, 95% CI 0.71–1.40). Median PFS by independent review committee was 9.2 mo with IPAT + PAC vs. 8.5 mo with PBO + PAC (HR 0.79, 95% CI 0.56–1.13). In both arms, objective response rate was 47% and median response duration was 9.2 mo. Overall survival (OS) results are immature (deaths in 25%). Median PAC duration was 6.9 mo with IPAT + PAC vs. 8.8 mo with PBO + PAC; median duration of IPAT was 8.0 mo and PBO was 9.1 mo. IPAT + PAC was associated with more AEs leading to withdrawal of PAC (26% vs. 13%) or IPAT/PBO (11% vs. 4%). IPAT/PBO dose reductions were more common (34% vs. 8%) but PAC dose reductions (26% vs. 24%) and interruptions (53% vs. 51%) and IPAT/PBO interruptions (43% vs. 43%) were similar. No new safety signals were seen. The most common AEs were diarrhoea (85% vs. 37%; grade ≥3: 12% vs. 1%), alopecia (50% vs. 59%) and nausea (41% vs. 20%).

Conclusions

Adding IPAT to PAC did not improve efficacy in PIK3CA/AKT1/PTEN-altered HR+ aBC. The IPAT + PAC safety profile was consistent with known AEs of each agent. OS follow-up is ongoing.

Clinical trial identification

NCT03337724.

Editorial acknowledgement

Jennifer Kelly (Medi-Kelsey Ltd), funded by F. Hoffmann-La Roche.

Legal entity responsible for the study

F. Hoffmann-La Roche.

Funding

F. Hoffmann-La Roche.

Disclosure

N. Turner: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharpe and Dohme; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Honoraria (self), Advisory/Consultancy: Bicycle Therapeutics; Honoraria (self), Advisory/Consultancy: Taiho; Honoraria (self), Advisory/Consultancy: Zeno Pharmaceuticals; Honoraria (self), Advisory/Consultancy: Repare Therapeutics; Research grant/Funding (institution): BioRad; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Guardant Health. R. Dent: Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self): Novartis; Honoraria (self): Lilly; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Eisai; Honoraria (self), Travel/Accommodation/Expenses: Merck; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca. J. O'Shaughnessy: Honoraria (self), Advisory/Consultancy: AbbVie Inc; Honoraria (self), Advisory/Consultancy: Agendia; Honoraria (self), Advisory/Consultancy: Amgen Biotechnology; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Celgene Corporation; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Genentech; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: GRAIL; Honoraria (self), Advisory/Consultancy: Immunomedics; Honoraria (self), Advisory/Consultancy: Heron Therapeautics; Honoraria (self), Advisory/Consultancy: Ipsen Biopharmaceuticals; Honoraria (self), Advisory/Consultancy: Jounce Therapeutics; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Myriad; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Ondonate Therapeutics; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Puma Biotechnology; Honoraria (self), Advisory/Consultancy: Prime Oncology; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy: Syndax Pharmaceuticals; Honoraria (self), Advisory/Consultancy: Takeda. S-B. Kim: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Lilly; Advisory/Consultancy: Enzychem; Advisory/Consultancy: Dae Hwa Pharmaceutical Co. Ltd; Advisory/Consultancy: ISU Abxis; Advisory/Consultancy: Daiichi-Sankyo; Research grant/Funding (institution): Sanofi-Aventis; Research grant/Funding (institution): Kyowa-Kirin Inc; Research grant/Funding (institution): DongKook Pharm Co. S. Isakoff: Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Advisory/Consultancy: Hengrui; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Mylan; Advisory/Consultancy: Puma; Advisory/Consultancy, Research grant/Funding (institution): Oncopep Research ; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Merck. C.H. Barrios: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer-Ingelheim; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche/Genentech; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Covance; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): PharmaMar. S. Saji: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Takeda; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: Kyowa-Kirin; Honoraria (self): Eli Lilly; Honoraria (self): MSD; Honoraria (self): Pfizer; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Taiho Pharmaceutical. Z. Nowecki: Travel/Accommodation/Expenses: Roche. Q. Lian: Shareholder/Stockholder/Stock options: Roche; Shareholder/Stockholder/Stock options: AbbVie; Shareholder/Stockholder/Stock options: Gilead; Full/Part-time employment: GNE/Roche. S-J. Reilly: Full/Part-time employment: Roche. H. Hinton: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. M. Wongchenko: Full/Part-time employment: GNE/Roche; Shareholder/Stockholder/Stock options: Roche. A. Mani: Full/Part-time employment: GNE/Roche; Shareholder/Stockholder/Stock options: Roche. M. Oliveira: Advisory/Consultancy, Research grant/Funding (institution): GNE; Advisory/Consultancy, Research grant/Funding (institution): GSK; Advisory/Consultancy, Research grant/Funding (institution): PUMA Biotechnology; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Philips; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Zenith Epigenetics; Research grant/Funding (institution): Cascadian Therapeutics; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Celldex; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Piqur; Non-remunerated activity/ies, Member of Executive Board: SOLTI Breast Cancer Research Group. All other authors have declared no conflicts of interest.

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