American Society of Clinical Oncology (ASCO 2023)
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, to discuss the latest advancements in treatments, clinical trials research and cancer care.
The following is a summary of the key breast cancer clinical trials research results presented at ASCO 2023.
Findings from the NATALEE trial were presented at ASCO and showed that adding the CDK4/6 inhibitor ribociclib to endocrine therapy resulted in a significant improvement in invasive disease–free survival for patients with hormone-receptor positive, HER2-negative early-stage breast cancer.
Overall, the addition of ribociclib reduced the risk of disease recurrence by 25%. The invasive disease–free survival benefit seen in the ribociclib group was generally consistent across clinically relevant patient subgroups. Ribociclib also showed favourable outcomes in recurrence-free survival, and distant disease–free survival. More follow-up is needed to confirm the benefits.
EBCTCG Ovarian Suppression Meta-Analysis
A new meta-analysis of 25 studies dating back to 1948, including the SOFT and TEXT clinical trials conducted by Breast Cancer Trials, provides more evidence linking ovarian suppression/ablation in premenopausal women to reduce recurrence and improved survival in the long term, after early-stage breast cancer.
Suppressing ovarian function of women with breast cancer may improve outcomes by preventing estrogenic stimulation of any residual cancer, particularly for pre-menopausal women with estrogen receptor (ER)-positive tumours. This can be done by using an injection of medication such as goserelin or surgical removal of the ovaries.
Researchers found that for those who didn’t take tamoxifen – a standard treatment today – patients seemed to gain an especially large benefit. The randomized studies, which included 14,999 subjects, suggest that ovarian suppression/ablation can provide a substantial and persistent benefit for premenopausal women, reducing 15-year risk of recurrence and death from breast cancer without increasing mortality from other causes. Importantly, the benefits persisted for at least a decade after stopping treatment.
MonarchE Age Subgroup
Results from the MonarchE trial were presented at ASCO, where researchers reported efficacy and safety by age subgroups, to help guide management of older patients receiving adjuvant abemaciclib. Almost half of newly diagnosed breast cancers occur in women older than 65 years, who often have a higher incidence of comorbidities and increased risk for toxicities.
Adjuvant abemaciclib (a CDK4 & 6 inhibitor) combined with endocrine therapy, demonstrated a sustained benefit in invasive disease-free survival and a tolerable safety profile in patients with HR+, HER2-, node-positive, high-risk early breast cancer.
In patients with high-risk early breast cancer, adjuvant abemaciclib plus endocrine therapy showed treatment benefit across age subgroups with a manageable safety profile. Older patients did have higher rates of adverse events and discontinuations, especially those older than 75 years, suggesting that more frequent surveillance with early intervention may be key to the management of these patients. This treatment has been recommended for funding in Australia by the PBAC, so is expected to become available in the near future.
Trastuzumab Deruxtecan Age Analysis
Trastuzumab Deruxtecan is approved for use in patients with HER2+ unresectable or metastatic breast cancer, after a prior anti-HER2-based regimen in the metastatic or neoadjuvant setting. Older patients with HER2+ metastatic breast cancer tend to have worse efficacy and safety outcomes, regardless of treatment. But their outcomes when treated with Trastuzumab Deruxtecan have not been thoroughly examined.
Researchers presented results at ASCO on age-specific (<65 vs ≥65 years) efficacy and pooled safety analyses of treatment with Trastuzumab Deruxtecan from the DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03 clinical trials.
They found from this pooled analysis that treatment with Trastuzumab Deruxtecan has a favourable benefit-risk in patients older than 65 years. This treatment has shown remarkable activity and is expected to become available in Australia in the near future for patients with metastatic HER2+ breast cancer that has become resistant to initial therapy.
Most international guidelines recommend upfront use of a CDK4/6 inhibitor in the first-line setting in HR-positive, HER2-negative advanced breast cancer, despite the prolonged toxicity and marked costs that come with extended treatment. This is because several trials have shown that pairing a CDK4/6 inhibitor with endocrine therapy in the first-line setting improves both progression-free survival and overall survival. However, the combination also accomplishes this after initial treatment with endocrine monotherapy, and many patients can achieve lasting disease remission on first-line endocrine therapy alone.
The SONIA clinical trial compared the efficacy, safety, and cost-effectiveness of first- or second-line use of a CDK4/6 inhibitor when added to endocrine therapy in patients with HR-positive, HER2-negative advanced breast cancer, to provide better insight into the optimal sequencing strategy for these targeted agents in clinical practice.
Researchers found that while there were no marked differences in progression free survival or overall survival between the two cohorts, the time on treatment and the toxicity profiles for the different strategies painted a different picture. Patients who received a CDK4/6 inhibitor upfront remained on treatment for a median of 24.6 months, whereas patients who received it as second line remained on treatment for a median of 8.1 months—a difference of 16.5 months. This means that some patients may be able to have endocrine therapy alone as initial treatment, without impairing survival, with fewer side effects and costs.
SOFT/Text Analysis by Lauren Brown – PAM50
The landmark clinical trial called SOFT, in premenopausal breast cancer patients, revealed that the addition of ovarian function suppression (OFS) to adjuvant endocrine therapy with either tamoxifen (T+OFS) or exemestane (E+OFS), reduces the risk of recurrence compared with adjuvant tamoxifen alone. However, there are no biomarkers to aid decision-making about intensification of endocrine therapy with OFS.
The purpose of this secondary analysis of the SOFT trial by Australian researchers, was to assess the prognostic and predictive ability of PAM50 intrinsic subtypes and ROR scores in premenopausal women with HR+/HER2- breast cancer in the SOFT trial.
They found that subtype distribution significantly differed between very young vs young premenopausal women, with fewer luminal A and more luminal B and non-luminal tumours seen in the very young. The ROR score distribution also differed significantly: in node-negative patients there were significantly more ROR-high scores amongst very young compared to young women (36% vs 14%. Therefore, the ROR score can be considered to inform the prognosis of premenopausal patients with early-stage breast cancer.
The typical dose of oral capecitabine chemotherapy for metastatic breast cancer internationally is 1250 mg/m2 twice daily, administered in a 14-day on, 7-day off schedule, cycled every 21 days. However, this dose has been associated with poor tolerability and increased toxicities, often leading to treatment discontinuation. There has been a growing question regarding oral capecitabine’s optimal dosing and duration, aiming to minimize toxicity while maintaining efficacy.
The randomized clinical trial X-7/7 comparing the standard dose capecitabine (1250 mg/m2 twice daily 14 days on followed by 7 days off) with fixed-dose (1500 mg orally twice daily, 7 days on followed by 7 days off).
The study found that patients receiving a fixed-dose of capecitabine (lower than the current standard dose) on a regimen of 7 days on/7 days off experienced less toxicity and similar survival compared with those treated with the standard capecitabine therapy regimen. So fixed-dose 7/7 may be an alternative dosing option to minimize toxicity while maintaining outcomes in metastatic breast cancer.
BWEL is a randomized study evaluating the impact of a telephone-based weight loss intervention in patients with stage II or III breast cancer who are overweight or obese. The study found that the intervention resulted in clinically significant weight loss in the patients receiving the intervention compared with a control group. Weight control is often challenging after a diagnosis and treatment for early-stage breast cancer, despite evidence that increased weight is associated with higher chance of cancer recurrence and other adverse outcomes.
A telephone-based weight loss intervention induced significant, clinically meaningful weight loss in patients with stage II/III breast cancer who are overweight or obese across demographic and tumour factors, but not across menopausal status or race/ethnicity. According to the study’s results, patients receiving the intervention lost an average of 4.8% (± 7.9%) of baseline body weight at 12 months vs 0.8% (± 6.4%) weight gain in the control group.
This is encouraging that it is possible to lose a meaningful amount of weight after a diagnosis of breast cancer with appropriate support. This in itself has a beneficial effect on cardiovascular outcomes and general wellbeing. Longer follow-up of the study will evaluate whether the intervention improves disease outcomes.
CANKADO is an app in development that supports patients during their treatment journey by providing a digital patient diary, web and app-based support, documentation of patient-reported outcomes and physician-patient interaction.
The PreCycle clinical trial evaluated the impact of CANKADO on quality of life in patients with metastatic breast cancer patients receiving palbociclib and an aromatase inhibitor, or palbociclib and fulvestrant.
The study found that patients receiving oral tumour therapy reported a significant benefit when using the interactive app. This app is not yet currently available, but these type of apps are on the horizon and hold great promise in supporting patients’ optimal quality of life.