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Key Data From SABCS 2020: A European Perspective

Javier Cortes, MD, PhD

Head, Breast Cancer Program
IOB Institute of Oncology
Madrid and Barcelona, Spain


Javier Cortes, MD, PhD, has disclosed that he has received funds for research support (paid to his institution) from Ariad, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer, Eisai, F. Hoffmann-La Roche, Guardant Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma, Roche, and Queen Mary University of London and consulting fees from AstraZeneca, Athenex, Bioasis, Biothera, Celgene, Cellestia, Clovis Oncology, Daiichi Sankyo, Erytech, GlaxoSmithKline, Leuko, Lilly, MedSIR, Merck Sharp & Dohme, Merus, Polyphor, Roche, Seattle Genetics, and Servier.


View ClinicalThoughts from this Author

Released: March 8, 2021

At the 2020 San Antonio Breast Cancer Symposium (SABCS), many exciting results were presented in the metastatic breast cancer (MBC) and early breast cancer (EBC) settings. In this commentary, I will discuss 6 key studies presented at SABCS 2020 and my thoughts on their implications for clinical practice.

Metastatic Breast Cancer

KEYNOTE‑355
Immunotherapy plus chemotherapy is an important treatment option as initial therapy for patients with PD-L1–positive advanced triple-negative breast cancer (TNBC), but the optimal chemotherapy partner remains a matter of debate. Trials addressing this issue have had mixed success, and negative results were recently reported for atezolizumab plus paclitaxel in the phase III IMpassion131 trial at ESMO 2020. At SABCS 2020, we presented data on the phase III KEYNOTE-355 trial, which evaluated pembrolizumab or placebo plus either nab-paclitaxel, paclitaxel, and gemcitabine/carboplatin in previously untreated patients with advanced TNBC. In patients with a PDL1≥ 10, the ORR was higher in patients who received pembrolizumab with chemotherapy compared with chemotherapy alone (53.2% vs 39.8%). In addition, a significant PFS benefit was observed for pembrolizumab plus chemotherapy in patients with a PD-L1 combined positive score ≥ 10 (HR: 0.65). This benefit was across chemotherapies, which is very important because it indicates that paclitaxel, nab-paclitaxel, and carboplatin/gemcitabine are all appropriate partners for pembrolizumab. In fact, these data led to an accelerated FDA approval for pembrolizumab plus chemotherapy in patients with locally recurrent unresectable or metastatic TNBC and a tumor PD-L1 combined positive score ≥ 10.

IPATunity130
Alterations in the AKT/PI3K signaling pathway are common in patients with TNBC and are potential treatment targets. Previously, the phase II LOTUS trial reported improved PFS in women with advanced TNBC who received the AKT inhibitor ipatasertib in combination with paclitaxel as first-line therapy. Primary data from the follow-up, double-blind phase III IPATunity130 trial were presented at SABCS 2020 for patients with PIK3CA/AKT1/PTEN-altered locally advanced unresectable or metastatic TNBC. The IPATunity130 trial showed that first-line ipatasertib plus paclitaxel did not improve PFS compared with placebo plus paclitaxel (HR: 1.02; log-rank P = .9237). The ongoing placebo-controlled phase III CAPItello-290 trial (NCT03997123) is evaluating the AKT inhibitor capivasertib plus paclitaxel, but for now, there are no phase III data suggesting that AKT inhibitors plus paclitaxel improve patient outcomes.

CONTESSA
CONTESSA is a randomized, open-label phase III study of tesetaxel (an oral taxane) plus capecitabine versus capecitabine alone in patients with hormone receptor–positive, HER2‑negative MBC who previously received taxane therapy. At SABCS 2020, the first data were presented for CONTESSA, revealing a significant PFS benefit (HR: 0.716, P = .003) and an increased ORR for the combination of tesetaxel and capecitabine vs capecitabine alone (57% vs 41%, P = .0002). Although I think that this is an important study, an important criticism is that doublet chemotherapy is not the usual standard of care and does not increase OS compared with sequential single-agent therapy. However, I think that this could be a good treatment option for patients who have a heavy tumor burden and are very symptomatic.

DESTINY‑Breast01
DESTINY‑Breast01 was a large, open-label phase II trial evaluating trastuzumab deruxtecan in heavily pretreated patients with HER2‑positive MBC. At SABCS 2020, PFS and OS data were updated from the study’s publication in the New England Journal of Medicine in 2020. At a median follow-up of 20.5 months, the updated median PFS was 19.4 months, which compares favorably with other anti‑HER2 therapies in this setting. The median OS was 24.6 months, which was higher than expected. Based on the data from this trial, trastuzumab deruxtecan received accelerated approval from the FDA in December 2019 and conditional authorization from the EMA at the end of January 2021 as monotherapy for adults with unresectable or metastatic HER2-positive breast cancer who have received at least 2 previous HER2-targeted regimens. The EMA will review additional evidence for trastuzumab deruxtecan after data are available from the phase III DESTINY-Breast02 trial (NCT03523585), but I think it is wonderful news that we can use it in the meantime for our patients in Europe.

Early Breast Cancer
In the EBC setting, I want to highlight 2 key studies: monarchE and RxPONDER.

monarchE
The monarchE trial was the first randomized phase III study of the CDK4/6 inhibitor abemaciclib in combination with endocrine therapy for patients with high‑risk, hormone receptor–positive, HER2‑negative EBC. Patients were randomized to standard of care endocrine therapy (ET) with or without abemaciclib. The primary endpoint of invasive disease‑free survival (iDFS) was achieved at the median follow-up of 19.1 months with the 2‑year iDFS superior in the abemaciclib arm vs ET alone (92.2% vs 88.7%, respectively; HR: 0.75, P = .01). In my opinion, the combination of abemaciclib and endocrine therapy is something important to be considered for appropriate patients with high-risk hormone receptor–positive, HER2‑negative EBC for clinical practice in the future.

RxPONDER
RxPONDER may have been the most important study presented at SABCS 2020. In this trial, patients with hormone receptor–positive, HER2‑negative EBC with 1-3 positive lymph nodes and a recurrence score ≤ 25 were randomized to receive chemotherapy followed by ET or ET alone. At SABCS 2020, iDFS data were presented at a median follow-up of 5.1 years, showing a 1.4% improvement in iDFS favoring chemotherapy plus ET (HR: 0.81, P = .026). In agreement with the TAILORx and MINDACT trials, no benefit was observed for adding chemotherapy in postmenopausal women with a low recurrence score. So we can safely spare chemotherapy for postmenopausal women with a low recurrence score, even if there is positive lymph node involvement. However, among premenopausal women there was a 5.2% improvement in iDFS favoring chemotherapy plus ET (HR: 0.54, P = .0004). I think that it is very important for us to consider chemotherapy as a standard of care for premenopausal women independently of their recurrence score.

Conclusion
Many important data came from SABCS 2020, but I want to reiterate a few key findings.

  • Paclitaxel, nab‑paclitaxel, and gemcitabine/carboplatin are all good chemotherapy partners for pembrolizumab in patients with PD-L1–positive inoperable or metastatic TNBC.
  • The AKT inhibitor ipatasertib did not improve PFS in combination with paclitaxel even though the AKT/PI3K signaling pathway is activated during metastatic breast cancer.
  • Trastuzumab deruxtecan should be considered an important treatment option for third-line or beyond in pretreated patients with HER2-positive metastatic breast cancer.
  • It is important to continue chemotherapy in premenopausal women with hormone receptor–positive, HER2‑negative early breast cancer with positive axillary nodes regardless of recurrence score.

In summary, the studies presented at SABCS 2020 highlight important new advances in the treatment of patients with both metastatic and early breast cancer.

Your Thoughts
How will these studies and other data from SABCS 2020 influence your clinical practice for patients with metastatic breast cancer or early breast cancer? Please share your perspective in the comment section below.

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Supported by an educational grant from
Daiichi Sankyo, Inc.

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