With the San Antonio Breast Cancer Conference (SABCS) 2020 by AACR just completed, several new and clinical relevant phase 2 and phase 3 have been published in the Journal of the American Medical Association, Clinical Cancer Research, New England Journal of Medicine, Journal of Clinical Oncology, and Lancet Oncology.

[‘mediPr] provides you with an overview.

Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomised Clinical Trial

Hope S Rugo et al.

SOPHIA trial by Rugo et al. found statistically significant improved PFS with margetuximab plus chemotherapy compared with trastuzumab plus chemotherapy in ERBB2-positive ABC after progression on 2 or more prior anti-ERBB2 therapies. The trial was a phase 3 randomised open-label trial that enrolled 536 patients, with sequential primary endpoints of PFS and OS.

NCT02492711      PMID: 33480963     DOI: 10.1001/jamaoncol.2020.7932

Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study

Erica L Mayer et al.

PALLAS trial by Mayer et al. found adjuvant palbociclib for 2 years did not improve invasive DFS compared with adjuvant endocrine therapy alone in patients with stage II-III histologically confirmed HR+, HER2- breast cancer. The trial is an ongoing, multicentre, open-label, randomised phase 3 trial enrolling 5760 patients, with a primary endpoint of invasive DFS in the ITT population.

NCT02513394       PMID: 33460574        DOI: 10.1016/S1470-2045(20)30642-2

Adjuvant S-1 plus endocrine therapy for oestrogen receptor-positive, HER2-negative, primary breast cancer: a multicentre, open-label, randomised, controlled, phase 3 trial

Masakazu Toi et al.

Toi et al. conducted a multicentre, open-label, randomised, controlled phase 3 trial in patients with stage I to IIIB invasive breast cancer, comparing standard adjuvant endocrine therapy with or without 1 year of S-1. The S-1 group had significantly improved invasive DFS, suggesting the combination could be a potential treatment option for intermediate and high-risk ER+, HER2- patients.

PMID: 33387497       DOI: 10.1016/S1470-2045(20)30534-9

Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study

Antoinette R Tan et al.

FeDeriCa trial by Tan et al. found the fixed-dose combination of pertuzumab and trastuzumab as subcutaneous injection was non-inferior to intravenous administration in the neoadjuvant setting, in terms of cycle 7 pertuzumab serum trough concentrations. The trial was a randomised, open-label, multicentre non-inferiority phase 3 trial enrolling 252 patients to receive either intravenous pertuzumab and trastuzumab, or the subcutaneous fixed-dose combination of the two. Primary endpoint was non-inferiority of the cycle 7 pertuzumab serum trough concentration.

NCT03493854       PMID: 33357420       DOI: 10.1016/S1470-2045(20)30536-2

Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): an open-label, multicentre, parallel-group, randomised, phase 3 trial

Ian Smith et al.

The POETIC trial by Smith et al. found POAI therapy did not improve treatment outcome but can be used to select appropriate adjuvant therapy based on Ki67. The trial was an open-label, multicentre, parallel-group, randomised phase 3 trial enrolling 4480 postmenopausal women to receive either POAI for 14 days preceding and following surgery, or no POAI. The primary endpoint was time to recurrence, and secondary endpoint was association between Ki67 and disease outcome.

NCT02338310       PMID: 33152284       PMC: PMC7606901       DOI: 10.1016/S1470-2045(20)30458-7

Internal mammary and medial supraclavicular lymph node chain irradiation in stage I-III breast cancer (EORTC 22922/10925): 15-year results of a randomised, phase 3 trial

Philip M Poortmans

The 15-year analysis of EORTC 22922/10925 by Poortmans et al. found IM-MS irradiation in stage I-III breast cancer led to significant reduction in breast cancer mortality and any breast cancer recurrence, but did not translate to improved OS. The trial was a randomised, phase 3 trial enrolling 4004 patients to receive either IM-MS irradiation or no IM-MS radiation, with a primary endpoint of overall survival.

NCT00002851       PMID: 33152277       DOI: 10.1016/S1470-2045(20)30472-1

Effect of Taxane Chemotherapy With or Without Indoximod in Metastatic Breast Cancer: A Randomised Clinical Trial

Veronica Mariotti et al.

A phase 2, double-blinded, placebo-controlled randomised trial by Mariotti et al. found the addition of indoximod to a taxane did not improve PFS compared with a taxane alone in ERBB2-negative MBC. The trial randomised 169 patients, with a primary endpoint of PFS and secondary endpoints of median OS, ORR, and safety.

NCT01792050       PMID: 33151286       PMC: PMC7645745       DOI: 10.1001/jamaoncol.2020.5572

Efficacy of Circulating Tumor Cell Count-Driven vs Clinician-Driven First-line Therapy Choice in Hormone Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer: The STIC CTC Randomised Clinical Trial

François-Clément Bidard et al.

The STIC CTC trial by Bidard et al. found CTC count may be a reliable biomarker for choosing between chemotherapy and endocrine therapy as first-line treatment in HR+, ERBB2- MBC. The trial enrolled 755 patients randomised to either CTC arm where chemotherapy or endocrine therapy was chosen according to CTC count (chemotherapy if ≥5CTCs/7.5 mL; endocrine therapy if <5 CTCs/7.5 mL), or control arm, where treatment choice was investigator-chosen, with a primary endpoint of investigator-assessed PFS. NCT01710605       PMID: 33151266       PMC: PMC7645742       DOI: 10.1001/jamaoncol.2020.5660

Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial

Leisha A Emens et al.

KATE2 trial by Emens et al. found addition of atezolizumab to trastuzumab emtansine did not lead to clinical improvement in PFS and was associated with more adverse events. The trial was a randomised, double-blind, placebo-controlled phase 2 trial enrolling 202 patients with HER2+ ABC, with a primary endpoint of investigator-assessed PFS in the ITT population.

NCT02924883       PMID: 33002436       DOI: 10.1016/S1470-2045(20)30465-4

Effect of Eribulin With or Without Pembrolizumab on Progression-Free Survival for Patients With Hormone Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer: A Randomised Clinical Trial

Sara M Tolaney et al.

A multicentre, randomised, phase 2 clinical trial by Tolaney et al. found the addition of pembrolizumab to eribulin did not improve PFS, OS, or ORR compared with eribulin alone in patients with HR+, ERBB2- MBC who had received 2 or more lines of hormonal therapy and 0-2 lines of chemotherapy. The trial enrolled 88 patients who were randomised 1:1, with a primary endpoint of PFS, and secondary endpoints of OS and ORR.

NCT03051659       PMID: 32880602       PMC: PMC7489368       DOI: 10.1001/jamaoncol.2020.3524

Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial

Véronique Diéras et al.

BROCADE3 trial by Diéras et al. found the addition of veliparib to a platinum doublet resulted in significant and durable PFS improvements in ABC patients with germline BRCA mutations. The trial was a randomised, double-blind, placebo-controlled phase 3 trial enrolling 513 patients randomised 2:1 to carboplatin and paclitaxel combined with veliparib, or matching placebo. The primary endpoint was investigator-assessed PFS.

NCT02163694       PMID: 32861273       DOI: 10.1016/S1470-2045(20)30447-2

Effect of Adjuvant Paclitaxel and Carboplatin on Survival in Women With Triple-Negative Breast Cancer: A Phase 3 Randomised Clinical Trial

Ke-Da Yu et al.

PATTERN trial by Yu et al. found that paclitaxel plus carboplatin regimen as an alternative adjuvant chemotherapy choice was effective in patients with operable TNBC. The phase 3 randomised trial compared 6 cycles of paclitaxel plus carboplatin with the standard-dose regimen of 3 cycles of CEF-T in 647 patients, with a primary endpoint of DFS.

NCT01216111       PMID: 32789480       PMC: PMC7426881       DOI: 10.1001/jamaoncol.2020.2965

Association of Event-Free and Distant Recurrence-Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer: Three-Year Follow-up Analysis for the I-SPY2 Adaptively Randomised Clinical Trial

Douglas Yee et al.

Three-year follow up of the I-SPY2 trial by Yee et al. found achieving pCR after neoadjuvant therapy implies an 80% reduction in recurrence rate that is regardless of treatment regimen or subtype. The trial was a multicentre neoadjuvant platform phase 2 trial enrolling 950 patients who were randomised to one of several different investigational regimens or control therapy within molecular subtypes, to evaluate the association of pCR with EFS and distant recurrence-free survival.

NCT01042379       PMID: 32701140       PMC: PMC7378873       DOI: 10.1001/jamaoncol.2020.2535

Abbreviations:

ABC, advanced breast cancer; CEF-T, cyclophosphamide, epirubicin, fluorouracil, docetaxel; CTC, circulating tumour cell; DFS, disease-free survival; EFS, event-free survival; ER+, oestrogen receptor positive; ERBB2+ / HER2+, human epidermal growth factor receptor positive; ERBB2- / HER2-, human epidermal growth factor receptor negative; HR+, hormone receptor positive; IM-MS, internal mammary and medial supraclavicular; ITT, intention-to-treat; MBC, metastatic breast cancer; ORR, objective response rate; OS, overall survival; pCR, pathologic complete response; PFS, progression-free survival; POAI, preoperative and postoperative aromatase inhibitor; S-1, Tegafur/gimeracil/oteracil; TNBC, triple negative breast cancer