Using Genomics to Match Treatments Improved Outcomes for Certain Patients With Metastatic Breast Cancer
The ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) was highly predictive of the benefits of targeted therapies matched to genomic alterations
The use of multigene sequencing as a therapeutic decision tool improved the outcomes for patients with metastatic breast cancer when the genomic alterations identified were ranked in the I/II tiers of the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT), according to results from the SAFIR02-BREAST trial presented at SABCS during Tuesday morning’s General Session.
“Multigene sequencing has been widely implemented but its clinical impact and the best framework for its use are unclear,” said presenter Fabrice André, MD, PhD, research director at Gustave Roussy Cancer Campus. “The main purpose of our study was to test whether genomic analyses are useful for patients with metastatic breast cancer, and how we can best analyze the results.”
The phase II SAFIR02-BREAST trial enrolled patients with metastatic, HER2-negative breast cancer to evaluate whether targeted therapies guided by genomics improve progression-free survival (PFS) compared to maintenance chemotherapy. Patients who had received more than two lines of chemotherapy or one of the targeted therapies evaluated in the trial were not eligible to participate.
The researchers performed a pooled analysis of this trial and the SAFIR-PI3K trial that compared a combination of the PI3Kα-specific inhibitor alpelisib and the estrogen receptor antagonist fulvestrant with maintenance chemotherapy in patients with PIK3CA-mutated metastatic breast cancer.
“Our study showed that genomic analysis improves the outcome of patients with metastatic breast cancer if they carry alterations classified as ESCAT I/II,” Dr. André said. “These findings suggest that genomics should be a part of the pathway of care, but it has no impact if the results are not interpreted using a validated framework of actionability of the gene alterations identified.”
Abstract: GS1-10 Clinical utility of molecular tumor profiling: Results from the randomized trial SAFIR02-BREAST
Click here to read the full press release from the American Association for Cancer Research (AACR).
Single-cell Spatial Analysis May Help Predict Response to Neoadjuvant Immunotherapy in Triple-negative Breast Cancer
Imaging mass cytometry was feasible in a large clinical trial of atezolizumab in combination with chemotherapy
A next-generation technology that allows the study of protein expression at the single-cell level and the location of the cells within the tumor microenvironment (TME) was feasible and provided information on the benefit of adding the immune checkpoint inhibitor atezolizumab to chemotherapy as neoadjuvant treatment for patients with early high-risk and locally advanced triple negative breast cancer (TNBC), according to results presented at SABCS during Tuesday morning’s General Session.
“We are experiencing a revolution in the technologies available for characterizing the molecular complexity of tumors,” said presenter Giampaolo Bianchini, MD, Head of the Breast Cancer Group in the Department of Clinical Oncology at IRCCS Ospedale San Raffaele, Milan. “Among these, imaging mass cytometry (IMC) allows us to collect unprecedented information about the heterogeneity of tumors and their surrounding microenvironment.”
Emerging evidence has shown that TNBC tumors are infiltrated with mononuclear cells and lymphocytes. Combining immune checkpoint inhibition and chemotherapy demonstrated a significant benefit for high-risk TNBC patients in the KEYNOTE-522 trial, leading to the FDA approval of pembrolizumab in combination with chemotherapy as neoadjuvant therapy in this setting.
Dr. Bianchini and colleagues investigated whether IMC could assist in the identification of ideal candidates for this therapeutic approach. They performed IMC analysis in the context of the phase III NeoTRIPaPDL1 trial, which was designed to evaluate the addition of atezolizumab to the chemotherapeutics carboplatin and nab-paclitaxel, compared with carboplatin and nab-paclitaxel only, as neoadjuvant therapy in patients with early high-risk and locally advanced TNBC who underwent surgery within six weeks of finishing the treatment.
“Our results demonstrated that spatial data on the interactions among specific cells in the TME might be very informative about the benefit provided by an immune checkpoint inhibitor such as atezolizumab in addition to chemotherapy,” Dr. Bianchini said. “This type of information can only be provided by technologies that allow us to simultaneously characterize the single cells and their spatial localization with precision.”
Abstract: GS1-00 Single-cell spatial analysis by imaging mass cytometry and immunotherapy response in triple-negative breast cancer (TNBC) in the NeoTRIPaPDL1 trial
Click here to read the full press release from the American Association for Cancer Research (AACR).
The following abstracts were also presented during Tuesday’s General Session. These presentations will be available to registered SABCS participants for on-demand viewing until March 10, 2022. Click here to find these and other abstracts presented this week at SABCS 2021.
GS1-01 KEYNOTE-522 study of neoadjuvant pembrolizumab + chemotherapy vs placebo + chemotherapy, followed by adjuvant pembrolizumab vs placebo for early-stage TNBC: Event-free survival sensitivity and subgroup analyses
GS1-02 Final results of KEYNOTE-355: Randomized, double-blind, phase 3 study of pembrolizumab + chemotherapy vs placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer
GS1-05 Datopotamab deruxtecan in advanced/metastatic HER2- breast cancer: Results from the phase 1 TROPION-PanTumor01 study
GS1-06 A randomized control phase III trial of entinostat, a once weekly, class I selective histone deacetylase inhibitor, in combination with exemestane in patients with hormone receptor positive advanced breast cancer
GS1-07 Adjuvant palbociclib in HR+/HER2- early breast cancer: Final results from 5,760 patients in the randomized phase III PALLAS trial
GS1-08 CCTGMA.32, a phase III randomized double-blind placebo-controlled adjuvant trial of metformin (MET) vs placebo (PLAC) in early breast cancer (BC): Results of the primary efficacy analysis (clinical trials.gov NCT01101438)
GS1-09 Inhibition of GPX4 induces preferential death of p53-mutant triple-negative breast cancer cells