Lessons From Adaptive Randomization: Spying the I-SPY2 Trial in Breast Cancer

Authors: Bishal Gyawali MD, PhD, and Saroj Niraula MD, MSc
View More View Less
Restricted access

Disclosures: The authors have disclosed that they have no financial interests, arrangements, or affiliations with the manufacturers of any products discussed in this article or their competitors.

Correspondence: Saroj Niraula, MD, MSc, University of Manitoba and CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB, R3E 0V9, Canada. Email: sniraula@cancercare.mb.ca
  • 1.

    Jardim DL, Schwaederle M, Hong DS, . An appraisal of drug development timelines in the era of precision oncology. Oncotarget 2016;7:5303753046.

  • 2.

    Prasad V, Mailankody S. Research and development spending to bring a single cancer drug to market and revenues after approval. JAMA Intern Med 2017;177:15691575.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Dowden H, Munro J. Trends in clinical success rates and therapeutic focus. Nat Rev Drug Discov 2019;18:495496.

  • 4.

    Bhatt DL, Mehta C. Adaptive designs for clinical trials. N Engl J Med 2016;375:6574.

  • 5.

    Harrington D, Parmigiani G. I-SPY 2—a glimpse of the future of phase 2 drug development? N Engl J Med 2016;375:79.

  • 6.

    Park JW, Liu MC, Yee D, . Adaptive randomization of neratinib in early breast cancer. N Engl J Med 2016;375:1122.

  • 7.

    Rugo HS, Olopade OI, DeMichele A, . Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med 2016;375:2334.

  • 8.

    Chien AJ, Tripathy D, Albain KS, . MK-2206 and standard neoadjuvant chemotherapy improves response in patients with human epidermal growth factor receptor 2-positive and/or hormone receptor-negative breast cancers in the I-SPY 2 trial. J Clin Oncol 2020;38:10591069.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    DeMichele AM, Moulder S, Buxton M, . Efficacy of T-DM1+pertuzumab over standard therapy for HER2+ breast cancer: results from the neoadjuvant I-SPY 2 trial. Presented at the AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, Louisiana.

    • Crossref
    • Export Citation
  • 10.

    Nanda R, Liu MC, Yau C, . Effect of pembrolizumab plus neoadjuvant chemotherapy on pathologic complete response in women with early-stage breast cancer: an analysis of the ongoing phase 2 adaptively randomized I-SPY2 trial. JAMA Oncol 2020;6:676.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Pusztai L, Han HS, Yau C, . Evaluation of durvalumab in combination with olaparib and paclitaxel in high-risk HER2 negative stage II/III breast cancer: results from the I-SPY 2 trial. Presented at the AACR Annual Meeting; April 27, 2020; virtual.

  • 12.

    Loibl S, O’Shaughnessy J, Untch M, . Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol 2018;19:497509.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Cortazar P, Geyer CE Jr. Pathological complete response in neoadjuvant treatment of breast cancer. Ann Surg Oncol 2015;22:14411446.

  • 14.

    Cortazar P, Zhang L, Untch M, . Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014;384:164172.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Gyawali B, Hey SP, Kesselheim AS. Evaluating the evidence behind the surrogate measures included in the FDA's table of surrogate endpoints as supporting approval of cancer drugs [published online April 22, 2020]. EClinicalMedicine, doi: https://doi.org/10.1016/j.eclinm.2020.100332journal

    • Search Google Scholar
    • Export Citation
  • 16.

    Gianni L, Pienkowski T, Im YH, . Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 2012;13:2532.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Baselga J, Bradbury I, Eidtmann H, . Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 2012;379:633640.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    von Minckwitz G, Procter M, de Azambuja E, . Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med 2017;377:122131.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Piccart-Gebhart M, Holmes E, Baselga J, . Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III adjuvant lapatinib and/or trastuzumab treatment optimization trial. J Clin Oncol 2016;34:10341042.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Niraula S, Amir E, Vera-Badillo F, . Risk of incremental toxicities and associated costs of new anticancer drugs: a meta-analysis. J Clin Oncol 2014;32:36343642.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Delaloge S, Cella D, Ye Y, . Effects of neratinib on health-related quality of life in women with HER2-positive early-stage breast cancer: longitudinal analyses from the randomized phase III ExteNET trial. Ann Oncol 2019;30:567574.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 666 666 666
PDF Downloads 148 148 148
EPUB Downloads 0 0 0