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ASCO 2022 BREAST CANCER RESEARCH SUMMARY

A summary of the key breast cancer research presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

American Society of Clinical Oncology (ASCO 2022)

The American Society of Clinical Oncology (ASCO) annual meeting is one of the world’s largest and most renowned cancer conferences, bringing together leading cancer researchers, including those from Breast Cancer Trials (BCT), to discuss the latest advancements in treatments, clinical trials research and cancer care.

As we enter this new post-COVID era, this year’s conference was held in Chicago and attendees could choose to attend in-person or online, allowing delegates to participate from all over the world.

The following is a summary of the key breast cancer clinical trials research that BCT and other groups presented at ASCO 2022.

DESTINY-Breast04: Establishing Trastuzumab Deruxtecan as a new standard of care for HER2-low metastatic breast cancer.

DESTINY-Breast04 is a global, randomised, phase 3 trial evaluating the effectiveness of trastuzumab deruxtecan compared to chemotherapy, in patients with HR-positive or HR-negative, HER2-low metastatic breast cancer. HER2-low breast cancer (IHC 1+, or 2+/ISH-negative) has not had targeted treatment until now.

DESTINY-Breast04 randomly assigned patients with HER2-low metastatic breast cancer, who had previously received 1 or 2 lines of chemotherapy, and enrolled 557 participants across multiple sites in Asia, Europe, and North America.

Results from the DESTINY-Breast04 clinical trial have shown that the use trastuzumab deruxtecan displayed impressive improvements in progression-free survival by 4.8 months and overall survival by 6.6 months, for patients with HER2-low metastatic breast cancer, compared to standard chemotherapy treatment. This establishes a new targeted therapy for approximately half the patients with metastatic breast cancer.

PROSPECT Trial Results: Some early breast cancer patients may be able to avoid radiation therapy.

Results from the PROSPECT clinical trial have shown that the use of preoperative breast MRI may identify patients with a low risk of recurrence who can safely avoid radiotherapy. The PROSPECT clinical trial was coordinated across Australia and New Zealand, by Breast Cancer Trials recruiting 201 trial participants.

PROSPECT included patients with early-stage breast cancer that appeared to be a single lump on mammogram and ultrasound and were planned for breast conserving surgery. They then had an MRI prior to surgery, and if the cancer was small and confined to a single location within one breast, they proceeded with surgery, but did not receive radiotherapy. This trial found that of all trial participants, an additional 11% had areas of cancer or pre-cancerous change identified by MRI (but not seen on standard scans), that required treatment. After an average of five years follow up, the chance of breast cancer returning within the breast (local recurrence rate) was a very low 1%. Therefore, MRI may be a future option for deciding which patients are can safely avoid radiotherapy after breast conserving surgery without compromising their outcomes. Click for more information.

Reanalysis of BIG 1-98, SOFT and TEXT: Historical early treatment effects of adjuvant endocrine therapy for breast cancer in high-risk subgroups.

As published in the ASCO post, results from the combined analysis of three studies revealed that when planning adjuvant therapy for such patients, oncologists should carefully weigh the benefits and toxicities of available treatments, whether alone or in combination.

Data from the BIG 1-98, TEXT and SOFT clinical trials, which compared tamoxifen and aromatase inhibitors as adjuvant therapy for patients with non-metastatic breast cancer, has been revaluated to assess issues regarding the short-term effectiveness of treatment, while also knowing the long-term results.

Data was extracted on high recurrence-risk patients to inform the understanding of trials that utilised CDK4/6 inhibitors. With two to three years of follow up, the impact of endocrine therapy with an aromatase inhibitor (letrozole, exemestane or anastrozole) over tamoxifen alone provided similar magnitude of results to endocrine therapy plus abemaciclib, which was utilised in the monarchE study. This provides new insight into the effects vs benefits of treatment, while emphasising the importance of long-term follow up in patients on trials of adjuvant therapy for early-stage breast cancer. Click for more information.

Updated FAKTION data showed that capivasertib in addition to fulvestrant extends the survival of participants with aromatase inhibitor-resistant ER-positive, HER2-negative advanced breast cancer.

The FAKTION clinical trial was a randomised, placebo-controlled, phase two trial that recruited postmenopausal adult women aged 18 years and over with inoperable ER-positive, HER2-negative, metastatic, or locally advanced cancer. Patients all received fulvestrant (as standard of care), and half received the study drug capavisertib.

As published in the Lancet Oncology, 69 were assigned to receive fulvestrant plus capivasertib while 71 received fulvestrant plus placebo. Results from the FAKTION trial found significant improvements in overall survival in the study participants who received fulvestrant and capavisertib. The average survival was 29.3 versus 23.4 months in the capivasertib vs placebo arms, respectively. It showed that the benefit appears limited to those patients whose tumours harbour specific alterations in the PTEN/AKT/PI3K pathway.

The first report of the CHARIOT clinical trial results displayed an overall response rate of 71.4% among patients using immunotherapy drugs in combination with chemotherapy.

Conducted within Australia by BCT, the CHARIOT clinical trial investigated whether using immunotherapy drugs together with standard chemotherapy is safe and effective in treating breast cancer before surgery, and if continuing immunotherapy after surgery keeps the immune system active. Patients had triple negative breast cancer that did not respond to standard anthracycline-based neoadjuvant chemotherapy.

Data from the phase 2 CHARIOT clinical trial displayed positive outcomes in both safety and overall results in treatment-refractory breast cancer, with patients achieving a clinical complete response rate of 57.1% and an overall response rate of 71.4%. Additionally, from our media release Professor Sherene Loi, the Study Chair of the CHARIOT clinical trial, says that longer term follow up is needed to help determine the overall effectiveness of this treatment approach and the benefits to patients.

“While we have seen some promising results in the pathological response rate of this treatment, the survival benefits of adding ipilimumab to treatment is currently unclear. So, the study will now continue the future follow-up of patients to determine event free survival (EFS) and overall survival (OS),” Professor Loi said.

Within the surgically removed tissue, 24% of patients had complete eradication of the cancer. Those patients whose cancer was completely eradicated within the breast and nearby lymph nodes had a very good prognosis. Click for more information.

The LUMINA clinical trial: Patients with Luminal A low risk breast cancer have a low local recurrence rate of 2.3% after breast conserving surgery without radiotherapy.

The LUMINA clinical trial, which was sponsored by the Canadian Breast Cancer Foundation and the Canadian Cancer Society, assessed the outcomes of women aged 55+ years who had a lower risk of breast cancer recurrence as determined by the stage and subtype of their cancer. Patients underwent breast conserving surgery, also referred to as a lumpectomy or a partial mastectomy, followed by five years of endocrine therapy. However, patients did not receive the radiation therapy that would usually be prescribed following breast conserving surgery.

Patients had Luminal A breast cancer subtype, which accounts for around 30-45% of all breast cancer diagnoses, as indicated by positive oestrogen receptors, negative HER2 receptors and a low proliferative index (Ki67 <13.25%). The primary outcome was a local recurrence rate of 2.3%, meeting the trial’s criteria for success and indicating that radiotherapy was unlikely to be beneficial in this group of patients. This was a single arm trial, without a comparison group. The BCT EXPERT trial is a randomised comparative trial designed to answer a similar question using different methodology to define low risk tumours, the PAM50 tumour genomic test.

Updated KEYNOTE-522 clinical trial results

Pembrolizumab, an anti-PD-1 therapy, has previously demonstrated benefits in combination with chemotherapy as neoadjuvant treatment for adults with locally advanced or early-stage triple-negative breast cancer, with a high risk of recurrence. The KEYNOTE-522 clinical trial is the first randomised, phase III trial of immunotherapy in early breast cancer.

This presentation was an update of the KEYNOTE-522 clinical trial, where the immunotherapy drug pembrolizumab was used in combination with chemotherapy, prior to surgery and was then continued after surgery. This strategy was found to reduce the risk of recurrence or death by 37%, compared to chemotherapy alone. This update included more detailed analysis of the degree of tumour response, showing that reduced response was linked to greater chance of the cancer returning. These patients remain in need of improved treatment options.

HER3 Update

A phase 1/2 trial of patritumab deruxtecan in HER3-positive metastatic breast cancer indicated worthwhile treatment impact in terms of overall response and progression-free survival. This trial included patients who had already received several other treatments, to which their cancer was resistant, indicating a poor prognosis.

The importance of this trial is that HER3 is a new biomarker that indicates a higher likelihood of response to this specific drug. Patritumab deruxtecan is expected to move into earlier lines of therapy and into phase 3 trials. Some of the patients had triple negative breast cancer, which traditionally does not have a routinely used biomarker to predict treatment effect. This trial opens up a targeted treatment pathway for these patients.

Other Research Presented at ASCO

  • NRG-BR002: Stereotactic radiotherapy and/or surgical resection to metastatic lesions does not prolong progression free survival when used as a treatment option for patients with oligometastatic breast cancer (4 or fewer metastases).
  • PALOMA 2: Among trial participants with previously untreated ER-positive, HER2-negative metastatic breast cancer, Palbociclib in combination with letrozole resulted in longer progression-free survival (24.8 months), than letrozole alone. However, the trial was unable to demonstrate a survival benefit.
  • TROPICS-02: This phase 3 study met the primary endpoint of 30% reduction in the risk of disease progression or death in HR+, HER2 negative, metastatic breast cancer with Sacituzumab govitecan, a novel antibody-drug conjugate.
  • SOLAR-1: Biomarker analysis from Phase 3 SOLAR-1 clinical trial, shows alpelisib in combination with fulvestrant has a clinical benefit regardless of Estrogen Receptor 1 (ESR1) mutations and genes that confer CDK4/6 resistance

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