Highlights on metastatic breast cancer 2

Dr Laure-Anne Teuwen, a medical oncologist at the University Hospital of Antwerp in Belgium, reports on four presentations from the 2024 ASCO conference’s rapid oral session on metastatic breast cancer.

The PALMARES-2 is a retrospective/prospective study that compared the real-world efficacy in terms of real-world PFS of first-line treatments palbociclib, ribociclib, and abemaciclib in around 1800 patients with HR+/HER2- metastatic breast cancer. In the whole cohort, abemaciclib and ribociclib were more effective than palbociclib, with adjusted HR of 0.71 and 0.81, respectively. In subgroup analysis, eight specific clinically relevant disease settings were evaluated. In endocrine-resistant disease, luminal B disease and premenopausal patients, similar to the overall population, abemaciclib and ribociclib outperformed palbociclib. In patients with poor performance status, abemaciclib was superior to palbociclib. For those with de novo metastatic disease, abemaciclib was more effective than both palbociclib and ribociclib. Ribociclib showed higher efficacy than palbociclib in patients with liver metastasis. In older patients or those with bone-only disease, all three CDK4/6 inhibitors demonstrated similar effectiveness. Overall survival data are not yet mature and are awaited to confirm these findings.

The BRIA-IMT study, a phase I/II trial, investigates the safety and efficacy of an allogeneic, off-the-shelf, GM-CSF-secreting whole-cell-based cancer vaccine. The vaccine was combined with a checkpoint inhibitor, either administered immediately with the vaccine or delayed, starting three weeks after the first vaccination. Among the 54 patients, activity was observed across all breast cancer subtypes, with a 12-week clinical benefit in 55% of patients. PFS benefit was more pronounced in HR+ and HER2+ disease, with responses noted in patients with CNS involvement. Upfront checkpoint inhibition did not significantly alter PFS but was chosen for the ongoing phase 3 trial due to its numerical advantage. Side effects were mild, and quality of life was not negatively impacted, so no participants discontinued treatment.

The TBCRC 048 trial is a phase 2 study evaluating olaparib monotherapy in an expansion cohort of patients with metastatic breast cancer, including those with gPALB2 mutations (n=24) or sBRCA mutations (n=30), until disease progression or unacceptable toxicity. The primary endpoint was the ORR, which was 75% in the gPALB2 cohort and 37% in the sBRCAm cohort. These results are promising, particularly for the gPALB2 cohort, a group with limited treatment options. For the sBRCAm cohort, identifying predictors of response will be crucial.

The final study is a retrospective cohort study examining genomic alterations and the use of targeted treatments in black versus white patients with ER+/HER2+ metastatic breast cancer. Black patients with PIK3CA alterations were significantly less likely to receive targeted therapy compared to white patients. There was no difference in the use of CDK4/6 inhibitors and mTOR inhibitors between the groups. None of the black patients with PIK3CA mutations were enrolled in clinical trials, whereas 12% of white patients were. Three significant differences in genomic alterations were noted: black patients with PR+ tumours were more likely to have CCND1 alterations, black patients with PR- tumours were more likely to have GATA3 alterations, white patients with PR- disease were more likely to have KRAS alterations. Black patients had significantly shorter OS than white patients in both the PR+ and PR- cohorts. It is crucial to understand the reasons behind these disparities in the use of PIK3CA-targeted therapy, clinical trial enrollment, and OS to address and improve racial disparities in breast cancer treatment.