PAKT Trial Phase II

Schimd P, Abraham J, Chan D, Wheatley D, Murray Brunt A, Nemsadze G, Baird RD, Hee Park YH, Hall PS, Perren T, Stein RC, Mangel L, Ferrero JM, Phillips M, Conibear J, Cortés J, Foxley A, de Bruin EC, McEwen R, Stetson D, Dougherty B, Sarker SH, Prendergast A, McLaughlin-Callan M, Burgess M, Lawrence C, Cartwright H, Mousa K, Turner NC. Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: The PAKT Trial. J Clin Oncol 2020; 38(5): 423-33

The PAKT randomized phase II clinical trial demonstrated that the addition of the AKT inhibitor capivasertib to treatment with first-line chemotherapy was associated with an improvement in progression-free survival and overall survival in patients with triple-negative metastatic breast cancer. This combination is currently being evaluated in a phase III clinical study (CAPItello 290).

DOI: 10.1200/JCO.19.00368

THE SANDPIPER Phase III

Dent R, Cortés J, Im YH, et al. Phase III randomized study of taselisib or placebo with fulvestrant in estrogen receptor-positive, PIK3CA-mutant, HER2-negative, advanced breast cancer: The SANDPIPER trial. Ann Oncol 2021; 32(2): 197-207

The phase III SANDPIPER clinical trial confirmed, as did the BELLE-2 clinical study, that the combination of the PI3K inhibitor taselisib with endocrine therapy is effective in postmenopausal women with RH-positive/HER2-negative endocrine-resistant advanced breast cancer. However, due to the side effect profile of both treatments, these therapeutic strategies have not been implemented in routine clinical practice.

DOI: 10.1016/j.annonc.2020.10.596

BELLE-2 Phase III

Baselga J, Im SA, Iwata H, Cortés J, et al. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): A randomized, double-blind, placebo-controlled, phase III trial. Lancet Oncol 2017; 18(7):904-16

The BELLE-2 phase III clinical trial showed that the combination of PI3K inhibitor buparlisib with endocrine therapy is effective in postmenopausal women with RH-positive/HER2-negative endocrine-resistant advanced breast cancer.

DOI: 10.1016/S1470-2045(17)30376-5

MONARCH 1 Phase II

Dickler MN, Tolaney SM, Rugo HS, Cortés J, Diéras V, Patt D, Wildiers H, Hudis CA, O’Shaughnessy J, Zamora E, Yardley DA, Frenzel M, Koustenis A, Baselga J. MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR+/HER2- metastatic breast cancer. Clin Cancer Res 2017; 23(17):5218-24

The MONARCH 1 phase II clinical trial confirmed the promising antitumour activity of the CDK4/6 inhibitor abemaciclib in patients with extensively pretreated RH-positive/HER2-negative metastatic breast cancer. This clinical trial led to the approval of abemaciclib as a single agent in the US for this patient group.

DOI: 10.1158/1078-0432.ccr-17-0754

Phase III study with vinflunine

Cortés J, Pérez-García J, Levy C, et al. Open-label randomized phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer. Ann Oncol 2020; 29(4):881-87

This phase III clinical trial showed no improvement in overall survival for the chemotherapy treatment vinflunine versus an alkylating agent in patients with highly pretreated advanced breast cancer. However, it is, together with the BEACON clinical trial, one of the most recent and relevant phase III studies to evaluate a new chemotherapy treatment in this context.

DOI: 10.1093/annonc/mdy051

BEACON Phase III

Pérez EA, Wada A, O’Shaugnessy J, Rugo H, Twelves C, Im SA, Gómez-Pardo P, Schwartzberg L, Diéras V, Yardley DA, Potter DA, Mailliez A, Moreno-Aspitia A, Ahn JS, Zhao C, Hoch U, Tagliaferri M, Hannah AL, Cortés J. Etirinotecan pegol (NKTR-102) versus treatment of physician’s choice in women with advanced breast cancer previously treated with and anthracycline, a taxane, and capecitabine (BEACON): A randomized, open-label, multicentre, phase III trial. Lancet Oncol 2015; 16(15):1556-68.

The BEACON phase III clinical trial showed no improvement in overall survival for the chemotherapy treatment etirinotecan pegol, compared to the physician’s treatment of choice, in patients with heavily pretreated advanced breast cancer. However, it is one of the latest and most important phase III studies to evaluate a new chemotherapy treatment in this context.

DOI: 10.1016/S1470-2045(15)00332-0

TRYPHANEA Phase II

Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsa YF, Ratnayake J, McNally V, Ross G, Cortés J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant 48 anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: A randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 2013; 24(9):2278-84

The TRYPHAENA phase II randomized clinical trial demonstrated a very significant increase in antitumour activity, in the form of a pathological complete response, with the addition of the anti-HER2 therapy pertuzumab to neoadjuvant treatment with chemotherapy and trastuzumab in patients with operable, locally advanced, or inflammatory HER2-positive breast cancer. This clinical trial, together with the NeoSphere study, led to the approval of pertuzumab in the US and Europe for this patient group.

DOI: 10.1093/annonc/mdt182

CLEOPATRA Phase III

Swain SM, Kim SB, Cortés J, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): Overall survival results from a randomized, double-blind, placebo-controlled, phase III study. Lancet Oncol 2013; 14(6):461-71

This paper confirmed that the addition of the anti-HER2 therapy pertuzumab to first-line treatment with chemotherapy and trastuzumab in patients with HER2-positive metastatic breast cancer, as well as improving progression-free survival as initially demonstrated, was also associated with a very significant increase in overall survival in this patient group.

DOI: 10.1016/S1470-2045(13)70130-X

301 Phase III

Kaufman PA, Awada A, Twelves C, Yelle L, Pérez EA, Velikova G, Olivo MS, He Y, Dutcus CE, Cortés J. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with antracycline and a taxane. J Clin Oncol 2015; 33(6):594-601

The 301 phase III clinical trial is the study that led to a modification of the SPC for eribulin in Europe, allowing the use of this chemotherapy treatment in patients with metastatic breast cancer previously treated with a single line of chemotherapy for advanced disease.

DOI: 10.1200/JCO.2013.52.4892

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