Highlights on metastatic breast cancer 1

Prof Dr François Duhoux, a medical oncologist at the Cliniques Universitaires Saint-Luc (Belgium), discusses the most remarkable presentations on metastatic breast cancer from ASCO 2024.

The first trial is the postMONARCH trial, a phase 3 study involving metastatic HR+, HER2- breast cancer patients who had progressed after treatment with an aromatase inhibitor and CDK4/6 inhibition. Patients were randomised to receive either abemaciclib and fulvestrant or fulvestrant alone. Patients receiving the combined treatment had a prolonged median PFS of 12.9 months, compared to 5.6 months for those receiving fulvestrant with a placebo. The benefit was observed across all subgroups but was more pronounced in patients without visceral metastasis.

In the INAVO120 trial, patients who had progressed on adjuvant endocrine therapy were randomised to receive palbociclib and fulvestrant with either inavolisib or a placebo. Earlier results showed that adding inavolisib improved PFS from 7.3 to 15 months. The data indicated that inavolisib also improved PFS2, the time between randomisation and progression to the second treatment or death, by nearly nine months. Patients treated with inavolisib received chemotherapy later, with a significant HR of 0.54. The updated safety and tolerability results demonstrated an increased likelihood of hyperglycaemia, rash, diarrhoea, and stomatitis occurring early in treatment. These results suggest that this triple therapy is promising for PIK3CA-mutated, HR+, HER2- metastatic breast cancer patients.

The phase 1b/2 DESTINY-Breast07 trial is the first to present data on HER2+ metastatic breast cancer patients treated with first-line T-DXd either as monotherapy or in combination with pertuzumab. Data from small cohorts showed an ORR of 76% and a median PFS of 80.8% at 12 months for patients treated with T-DXd (n=75), and 84% and 89.4%, respectively, for those treated with T-DXd/pertuzumab (n=50). The addition of pertuzumab increased the incidence of diarrhoea, but no additional safety signals were noted, including the absence of ILD.

Enfortumab Vedotin, a nectin-4-directed antibody-drug conjugate, is used in the EV-202 trial for triple-negative and HR+/HER2- metastatic breast cancer patients. Despite observed tumour activity, the response threshold was not reached. The response to EV was independent of nectin-4 expression levels, which were highly expressed in both cohorts.

Cohort C of the PATRICIA trial investigated a chemo-free regimen using palbociclib with trastuzumab and endocrine therapy in HER2+ patients with luminal A or luminal B disease versus the treatment of physician’s choice. The triplet combination led to a median PFS of 9.1 months compared to 7.5 months with the chemotherapy regimen.

Finally, the long-awaited results of the DESTINY-Breast06 trial were presented. This trial included HR+, HER2-low or HER2-ultralow metastatic breast cancer patients who had progressed after endocrine therapy. Patients were treated with T-DXd or the physician’s choice of treatment (capecitabine, nab-paclitaxel, paclitaxel). T-DXd treatment increased median PFS from 8.1 to 13.2 months. Immature OS results indicate a benefit from T-DXd treatment, and exploratory subgroup analysis showed increases in both PFS and OS for the ultralow category. Confirmed response rates varied from 56.5% to 61.8% in low and ultralow subgroups, compared to 32.2% in patients treated according to the physician’s choice. As expected, interstitial lung disease is a concern and needs to be monitored, but these data are practice-changing for HER2-low and HER2-ultralow breast cancer patients not pretreated with chemotherapy.