Presentations and discussions on the most recent findings and updates in oncology from around the world were covered at ASCO 2023. This article discusses some of the most important updates in breast cancer that are likely to change practice or will do so in the very near future.

Early breast cancer setting

EBCTCG Meta-analysis of breast cancer recurrence and survival following ovarian ablation or suppression in premenopausal women:

1. This meta-analysis involved patient-level data from 23 randomised trials involving nearly 15000 patients younger than age 55.
2. About half the women received no chemotherapy or received chemotherapy prior to randomisation, and their premenopausal status was confirmed afterwards while the other half received chemotherapy after randomisation. This could result in chemotherapy-induced menopause and would be expected to dilute the benefit of ovarian ablation or suppression.
3. For patients who had no chemotherapy or who remained premenopausal, a recurrence rate of 39.3% in the control group vs 29.5% in the ovarian ablation or suppression group was seen at 15 years.
4. This benefit grew over time, with the absolute difference rising from about 6% after 5 years to 8% after 10 years and 10% after 15 years. At 20 years, benefits of 10.9% for breast cancer–related mortality (RR = 0.71; P < .0000 and 11.6% for all-cause mortality (RR = 0.75; P < .0000 were seen in the ovarian ablation/suppression group who had no chemotherapy or who remained premenopausal.
5. These benefits were seen in both node-positive and node-negative groups. The absolute gains were higher in those not receiving tamoxifen although significant benefits were also seen in those taking tamoxifen.

NATALEE Phase 3 trial

1. It included men and pre/post-menopausal women from 20 different countries with stage IIA, IIB, or III hormone receptor–positive, HER2-negative breast cancer with a high risk of recurrence.

2. They were randomly assigned to receive either 400 mg of adjuvant ribociclib for 3 years with hormonal therapy for at least 5 years (n = 2,549) or hormonal therapy alone for at least 5 years.
3. The 3-year invasive disease–free survival rates were 90.4% in the ribociclib group compared with 87.1% in the hormonal therapy alone group, reducing the risk of disease recurrence by 25%.
4. The dose here is less than the 600mg used in metastatic breast cancer so that prolonged efficacy can be maintained while keeping it safe.

MonarchE 4-year update

1. At the 4-year timepoint in this previously published trial of adjuvant abemaciclib for two years in early breast cancer, the difference in invasive disease-free survival with abemaciclib was 6.4%, compared to a 4.8% difference at three years and a 2.8% difference at two years.

2. Thus, the magnitude of the benefit of this treatment approach appears to be increasing over time although overall survival data remain immature. Benefits were seen across all age groups and Ki-67 levels.

PHERgain Phase 2 study

1. This necessitates a novel approach that includes response evaluation and chemotherapy de-escalation. It enrolled patients from 45 European locations with HER2-positive, stage I to IIIA breast cancer that was at least 1.5 cm in size.
2. They received either HER2 blockade plus chemotherapy—docetaxel, carboplatin, trastuzumab, and pertuzumab(TCHP) (group A)—or HER2 therapy alone with trastuzumab and pertuzumab (group B). Patients had total-body F-18-FDG-PET scans after two cycles of the allocated medication.
3. Patients were designated PET responders if the scan revealed a 40% reduction in breast lesions from baseline. Following this, responders in the HER2-blockade-alone group (group B) received six more cycles of dual HER2 blockade (with the addition of endocrine treatment if necessary).
4. Non-responders in the HER2 blockade–alone group (group B) were switched to the TCHP group for six more cycles. Patients allocated to the HER2 blockade plus chemotherapy group (group A) received four extra cycles of TCHP regardless of response.
5. Patients had surgery after completing chemotherapy and were evaluated for pathologic full response. The key endpoints were concentrated on group B: the HER2 blockade-alone arm.
6. The first was pathologic complete response(PCR) in PET responders (ypT0/isN0) which was reported previously, and the second was 3-year invasive disease–free survival in that arm. In the adapted-response (HER2 blockade–alone) group, nearly 80% of patients achieved a response by PET; the 3-year invasive disease–free survival rate was 95.4%. In 37% of PET responders, complete PCR was also achieved.
7. Thus, around one-third of patients never received any chemotherapy, yet maintained a 3-year invasive disease-free survival rate of 98.8%.

Metastatic breast cancer setting 

PADA-1 Phase 3 trial update

1. Patients with ER Positive HER 2 negative metastatic breast cancer who displayed rising ESR1 mutations by ctDNA analysis in the blood (bESR1mut) during first-line aromatase inhibitors plus Palbociclib were randomised to continue treatment or switch to fulvestrant plus Palbociclib.
2. A new study confirmed the benefit of switching based on bESR1 mutation in terms of progression-free survival (PFS). ESR1 mutation type and clonality were not shown to be predictive of PFS.

PALMIRA Phase 2 study

1. Previously, the MAINTAIN research discovered that switching endocrine therapy while maintaining CDK4/6 inhibition led to increased PFS (2.76 vs 5.26 months), while the PACE study, which was similarly constructed, did not reveal a PFS improvement. PALMIRA investigated whether palbociclib plus a different endocrine therapy was more efficacious than endocrine therapy alone in women with metastatic breast cancer who had progressed on prior endocrine therapy plus Palbociclib.
2. Unfortunately, the findings from this study did not provide any convincing answers as to how to optimise outcomes in the second-line setting.
3. Median PFS was 4.9 months in the treatment group versus 3.6 months in the control group (HR 0.84, 95% CI [0.66, 1.07]; P = .149). However, the 6-month clinical benefit rate was significantly better in the combination group than the endocrine therapy-only group (41.9% vs 27.4%, P = .044), suggesting that a subset of patients might derive benefit by continuing with CDK4/6 inhibition in the second-line setting.

SONIA Phase 3 study

1. 1,050 women were randomly assigned to receive either first-line treatment with a nonsteroidal aromatase inhibitor (NSAI) plus a CDK4/6inhibitor, followed thereafter by single-agent fulvestrant upon disease progression, or first-line treatment with an NSAI, followed thereafter by fulvestrant plus a CDK4/6i upon progression.
2. No significant difference in time to progression on second-line therapy or overall survival was observed. First-line use did lead to a greater overall incidence of toxicity and higher drug costs owing to the longer treatment time.
3. However, with the changing landscape of treatment post CDK4/6 inhibitors, these findings might not be clinically relevant.

X-7/7 Phase 4 study

1. This randomised trial assessed the efficacy and tolerability of the standard FDA-recommended dose and schedule versus fixed-dose capecitabine 1,500 mg twice daily on a schedule of 7 days on and 7 days off (153 patients).
2. Significantly lower rates of treatment discontinuation, dose modifications, and grade 3 or higher toxicities with the fixed dosing schedule versus the standard were seen.
3. Furthermore, there were no significant differences in 3-month progression-free survival, objective response rate, or overall survival.

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Bipinesh Sansar, DM Medical Oncology, Associate Professor Medical Oncology at MPMMCC and HBCH, Varanasi.