This site is intended for healthcare professionals
breast core biopsy showing an invasive ductal carcinoma grade-II, most common form of breast cancer, cell image, pink overlay
  • Home
  • /
  • Medical education
  • /
  • SABCS 2022 Highlights – HER2-low, PARP inhibitors,...
  • /
  • New developments in HR+/HER2– therapy
SABCS 2022 Highlights – HER2-low, PARP inhibitors, and more

New developments in HR+/HER2– therapy

Read time: 15 mins
Last updated: 8th Mar 2023
Published: 16th Dec 2022
Author: Heather Mason and Ben Gallarda

In the following video, Professor Coombes gives his SABCS 2022 highlights on treatments for HER2– locally advanced or metastatic breast cancer.

Approved HR+/HER2– treatments

The treatment landscape of advanced and early HR+/HER2– breast cancer is evolving. Around a decade ago, endocrine therapy (ET) was added to HR+/HER2– metastatic breast cancer (MBC) therapy. Within the last five to six years, CDK4/6 trials in first- and second-line approaches have changed how patients with ER+ disease are managed. The MAINTAIN trial was the first randomised controlled trial to show PFS benefit in patients treated with palbociclib in the first line, who then switched to ribociclib following disease progression27.

Data from the SOLAR-1 trial showed improvement in PFS with PI3K inhibitor alpelisib in patients with PIK3CA mutant MBC without previous exposure to a CDK4/6 inhibitor28. These results led to FDA approval for alpelisib in 2019. In the BYLieve trial, patients previously treated with a CDK4/6i or aromatase inhibitors (AIs) subsequently received alpelisib (300mg daily) plus ET29. Previously presented data showed that over 50% of patients were without disease progression at six months, and updated results presented by Dr Hope Rugo showed 25.6% with long-term disease control (≥12 months PFS) and 16.5% with very long-term disease control (≥18 months).

Figure 1. Positive and negative prognostic factors for long-term disease control in PIK3CA-mutant, HR+/HER2– advanced breast cancer treated with alpelisib (Adapted29).

Figure 1. Positive and negative prognostic factors for long-term disease control in PIK3CA-mutant, HR+/HER2– advanced breast cancer treated with alpelisib (Adapted29).

In the TROPiCS-02 study, endocrine treatment-resistant patients with HR+/HER2– MBC were treated with the first-in-class Trop-2 antibody-drug conjugate sacituzumab govitecan (SG)30. A PFS and OS benefit was seen following SG treatment compared to treatment of physician's choice (TPC), regardless of Trop-2 expression. Caution should be taken due to small patient numbers.

In the following video, Professor Coombes discusses his SABCS 2022 highlights on triple negative breast cancer.

Figure 2. Diagram of Trop-2 antibody-drug conjugate sacituzumab govitecan (Adapted30).

Figure 2. Diagram of Trop-2 antibody-drug conjugate sacituzumab govitecan (Adapted30).

This year’s SABCS saw a good amount of research into later-line therapies after progression on standard-of-care targeted therapy in HR+/HER– breast cancer

Professor Coombes discusses HER2-high patients and possible resistance to trastuzumab deruxtecan (T-DXd).

An investigator-led study (TRIO-US-B-12 TALENT) presented by Dr Aditya Bardia evaluated T-DXd in the HER2-low early breast cancer (EBC) setting31. As there is cross-talk between oestrogen receptor (ER) and HER2, patients were treated with 6 or 8 treatment cycles of T-DXd with or without additional endocrine therapy (ET) (anastrozole). The objective response rate based on imaging was 68% in the T-Dxd arm and 58% in the T-Dxd plus ET arm. The primary endpoint of a 5% reduction in pathologic response rate (pCR) has only been achieved in one patient in the T-Dxd arm (5.3%). Following T-Dxd treatment, 48.6% of tumours had a change in immunohistochemical (IHC) staining; of these, 88.2% had a decrease in HER2 expression. These dynamic changes in HER2 staining following T-Dxd treatment might not reflect HER2 protein expression. The discordance between central or local review in biopsy samples highlights the need for better analytical tools and standardisation to identify HER2-low tumours. The addition of ET did not enhance the efficacy of T-Dxd, although due to the small patient number (n=29), these conclusions are made with caution.

Complete the form below to receive our regular round-up of the latest clinical news and medical education resources on Medthority, straight to your inbox.

* = required information 

 

By providing your email address, you are opting in to receive our monthly newsletter.

By submitting this form you agree to our Terms of Use and Privacy Policy. You can withdraw your consent at any time by clicking the ‘unsubscribe’ link found at the bottom of every email.

This content has been developed independently by Medthority who previously received educational funding from AstraZeneca in order to help provide its healthcare professional members with access to the highest quality medical and scientific information, education and associated relevant content.

References

  1. Krop I. Trastuzumab deruxtecan vs physician’s choice in patients with HER2+ unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine: Primary results of the randomized phase 3 study DESTINY-Breast02. Presented at the SABCS 2022, 7 December. San Antonio. GS2-01.
  2. Hurvitz SA. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results of the randomized, phase 3 study DESTINY-Breast03. Presented at the SABCS 2022, 7 December. San Antonio. GS2-02.
  3. Hurvitz SA, Hegg R, Chung WP, Im SA, Jacot W, Ganju V, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2022.
  4. Prat A, Bardia A, Curigliano G, Hammond MEH, Loibl S, Tolaney SM, et al. An Overview of Clinical Development of Agents for Metastatic or Advanced Breast Cancer Without ERBB2 Amplification (HER2-Low). JAMA Oncol. 2022.
  5. Rimm D. Discussion 1: Defining HER2 low: a pathologist's perspective. Presented at the SABCS 2022, 7 December. San Antonio. Special Session 3: HER2 Low: A Separate Entity?
  6. Prat A. Determination of HER2-low status in tumors of patients with unresectable and/or metastatic breast cancer in DESTINY-Breast04. Presented at the SABCS 2022, 7 December. San Antonio. Special Session 3: HER2 Low: A Separate Entity? HER2-18.
  7. Viale G. Retrospective Study to Estimate the Prevalence and Describe the Clinicopathological Characteristics, Treatment Patterns, and Outcomes of HER2-Low Breast Cancer. Presented at the SABCS 2022, 7 December. San Antonio. Special Session 3: HER2 Low: A Separate Entity? HER2-15.
  8. Harigopal M, Barlow WE, Tedeschi G, Porter PL, Yeh IT, Haskell C, et al. Multiplexed assessment of the Southwest Oncology Group-directed Intergroup Breast Cancer Trial S9313 by AQUA shows that both high and low levels of HER2 are associated with poor outcome. Am J Pathol. 2010;176(4):1639-1647.
  9. Koscielny S, Terrier P, Spielmann M, Delarue JC. Prognostic importance of low c-erbB2 expression in breast tumors. J Natl Cancer Inst. 1998;90(9):712.
  10. Curigliano G. Debate: Is HER2 low a separate entity? Presented at the SABCS 2022, 7 December. San Antonio. Special Session 3: HER2 Low: A Separate Entity?
  11. Denkert C, Seither F, Schneeweiss A, Link T, Blohmer JU, Just M, et al. Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials. Lancet Oncol. 2021;22(8):1151-1161.
  12. Raghavendra AS. Prevalence of HER2-low among Metastatic Breast Cancer Patients and Their Outcomes Compared to HER2 IHC 0. Presented at the SABCS 2022, 7 December. San Antonio. Special Session 3: HER2 Low: A Separate Entity? HER2-04.
  13. Zattarin E. HER2-Low Status is Associated with Worse Clinical Outcomes in Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer Patients Treated With First-Line Cyclin-Dependent Kinase 4/6 Inhibitors Plus Endocrine Therapy. Presented at the SABCS 2022, 7 December. San Antonio. Special Session 3: HER2 Low: A Separate Entity? HER2-02.
  14. Ahmed T. Molecular characterization of HER-2 low patients identifies basal-enriched subset with poor clinical outcomes in real-world data. Presented at the SABCS 2022, 7 December. San Antonio. Special Session 3: HER2 Low: A Separate Entity? HER2-08.
  15. Yam C. Clinical and Molecular Characteristics of HER2-low/zero Early Stage Triple-Negative Breast Cancer. Presented at the SABCS 2022, 7 December. San Antonio. Special Session 3: HER2 Low: A Separate Entity? HER2-01.
  16. Tolaney S. Debate: Is HER2 low a separate entity? Presented at the SABCS 2022, 7 December. San Antonio. Special Session 3: HER2 Low: A Separate Entity?
  17. Tarantino P, Jin Q, Tayob N, Jeselsohn RM, Schnitt SJ, Vincuilla J, et al. Prognostic and Biologic Significance of ERBB2-Low Expression in Early-Stage Breast Cancer. JAMA Oncol. 2022;8(8):1177-1183.
  18. Peiffer D. Epidemiology and Prognosis of HER2-Low Breast Cancer (BC) in the National Cancer Data Base (NCDB). Presented at the SABCS 2022, 7 December. San Antonio. Special Session 3: HER2 Low: A Separate Entity? HER2-11.
  19. Spring LM. Impact of HER2 low status on clinical outcomes in participants with 1-3 positive lymph nodes, HR+/HER2- breast cancer with recurrence score < / 25 randomized to endocrine therapy +/- chemotherapy: results from SWOG S1007 (RxPONDER). Presented at the SABCS 2022, 7 December. San Antonio. Special Session 3: HER2 Low: A Separate Entity? HER2-19.
  20. Fehrenbacher L, Cecchini RS, Geyer CE, Jr., Rastogi P, Costantino JP, Atkins JN, et al. NSABP B-47/NRG Oncology Phase III Randomized Trial Comparing Adjuvant Chemotherapy With or Without Trastuzumab in High-Risk Invasive Breast Cancer Negative for HER2 by FISH and With IHC 1+ or 2. J Clin Oncol. 2020;38(5):444-453.
  21. Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022;387(1):9-20.
  22. Marinho AD, Pessoa BMS, Brandao GR, Silva CHD, Reis PA, Comini ACM, et al. Efficacy of PARP Inhibitors in Patients With BRCA1/2-related Breast Cancer with Prior Platinum Exposure: A Systematic Review and Meta-Analysis. Presented at the SABCS 2022, 8 December. San Antonio. P4-01-08.
  23. Alés-Martínez JE, Balmaña J, Sánchez-Rovira P, Bofill FJS, García-Sáenz JÁ, Pimentel I, et al. Olaparib plus Trastuzumab in HER2[+] BRCA-Mutated Advanced Breast Cancer Patients: The OPHELIA Study. Presented at the SABCS 2022, 8 December. San Antonio. P4-07-29.
  24. Fasching PA, Schmatloch S, Hauke J, Rey J, Jackisch C, Klare P, et al. Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatinum in patients with HER2-negative breast cancer and homologous recombination deficiency – long-term survival of the GeparOLA study. Presented at the SABCS 2022, 9 December. GS5-02.
  25. Sammons SL, Tan TJ, Im YH, Traina TA, Anders C, Renzulli E, et al. DORA: A Phase II, Multicenter, International, Non-Comparator Study of Olaparib (O) +/- Durvalumab (D) as a chemotherapy-free maintenance strategy in Platinum tReated Advanced Triple-Negative Breast Cancer (aTNBC). Presented at the SABCS 2022, 8 December. San Antonio. PD11-12.
  26. Loirat D, barre MDdl, Villanueva C, Mailliez A, Isambert N, Moreau L, et al. Phase IV multicenter study evaluating RWE and the safety of talazoparib in patients with locally advanced or metastatic negative HER2 breast cancer and a BRCA1/2 mutation (ViTAL) - Cohort 2: patients treated according to the EMA. Presented at the SABCS 2022. San Antonio. P4-01-04.
  27. Kalinsky K, Accordino MK, Chiuzan C, Mundi PS, Trivedi MS, Novik Y, et al. A randomized, phase II trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition (CDK 4/6i) in patients (pts) with unresectable or hormone receptor–positive (HR+), HER2-negative metastatic breast cancer (MBC): MAINTAIN trial. Journal of Clinical Oncology. 2022;40(17_suppl):LBA1004-LBA1004.
  28. André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019;380(20):1929-1940.
  29. Rugo H. Long-Term and Very-Long-Term Disease Control in Patients From BYLieve Study Cohort A With PIK3CA-Mutant, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, Advanced Breast Cancer. Presented at the SABCS 2022, 9 December. San Antonio. PD13-06.
  30. Rugo H. Sacituzumab Govitecan (SG) vs Treatment of Physician’s Choice (TPC): Efficacy by Trop-2 Expression in the TROPiCS-02 Study of Patients (Pts) With HR+/HER2– Metastatic Breast Cancer (mBC). Presented at the SABCS 2022, 6 December. San Antonio. GS1-11.
  31. Bardia A. TRIO-US B-12 TALENT: Neoadjuvant trastuzumab deruxtecan with or without anastrozole for HER2-low, HR+ early stage breast cancer. Presented at the SABCS 2022, 7 December. San Antonio. GS2-03.