Co-authored by VHIO investigators, primary results from the multicenter TROPiCS-02 study of novel antibody-drug conjugate (ADC) sacituzumab govitecan in patients with hormone receptor-positive/HER2-negative (HR+/HER2-) endocrine-resistant, unresectable locally advanced or metastatic breast cancer, were selected as late breaking data by the American Society of Clinical Oncology (ASCO) at its Annual Meeting, 03 – 07 June 2022, Chicago (IL, USA).
Results of this phase III trial were presented during an Oral Abstract Session (1) by first author Hope S. Rugo, the University of California San Francisco – Hellen Diller Family Comprehensive Cancer Center (CA, USA).
ADCs are highly targeted therapies that deliver chemotherapy agents to tumor cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Upon linking to the targeted protein or receptor, they release a cytotoxic drug directly into the cancer cell, without damaging other surrounding cells. The anti-cancer payloads penetrate tumors and cause cell death either by damaging DNA of cancer cells or by preventing new ones from emerging, developing and spreading.
These potent contenders are showing increasing promise across several tumor types, several of which were discussed and debated throughout this week’s 2022 ASCO Annual Meeting including sacituzumab govitecan for the treatment of HR+/HER2- disease, the most common subtype of metastatic breast cancer.
“This subtype accounts for around 70% of all breast cancer cases. Therapy for these patients includes sequential endocrine therapy combined with targeted treatments followed by single-agent chemotherapy. Unfortunately, cancer drug resistance ultimately occurs in heavily treated patients, who have limited treatment options,” says Patricia Gómez, a Clinical Investigator of VHIO’s Breast Cancer Group directed by Cristina Saura, and a co-author of this phase III study.
The TROPiCS trial assessed the efficacy of sacituzumab govitecan, an ADC combining an anti-Trop-2 antibody with SN-38 chemotherapy versus treatment with physician’s choice (TPC). This ADC is approved by the U.S. Food and Drug Administration (FDA) for patients with metastatic triple-negative breast cancer who have received at least two prior therapies.
“Given that the Trop-2 protein is located on the surface of cells and is overexpressed in triple-negative breast cancer and in several other tumor types, we hypothesized that targeting Trop-2 could provide patients with HR+/HER2- metastatic breast cancer with an alternative treatment option,” adds Patricia Gómez, a Medical Oncologist at the Vall d’Hebron University Hospital’s Medical Oncology Department, headed by VHIO’s Director, Josep Tabernero.
Enrolling 543 patients who were randomized (1:1) to receive this ADC or treatment with physician’s choice, the TROPiCs investigators evaluated the efficacy of this novel agent in patients with HR+/HER2- tumors who had previously received at least one prior line of treatment with endocrine therapy, CDK4/6 inhibitors, and between two to four chemotherapy regimens.
Primary data show that sacituzumab govitecan achieved a statistically significant and clinically meaningful benefit versus single-agent chemotherapy, and a manageable safety profile in this patient population. In patients who received ADC, progression-free survival at six months was 46% compared to 30% in the chemotherapy group. At 12 months, progression-free survival was 21% versus 7%, respectively.
“While follow-up analysis will be required to assess the real impact on overall survival, these data show initial promise toward ringing in a new treatment option for these patients,” concludes Patricia Gómez, a co-investigator of this clinical trial.Putting liquid biopsy to the test in metastatic breast cancer
Results of two VHIO-led studies(2,3), selected by ASCO to first outing as poster communications, show the potential utility of liquid biopsy for the more precise, real-time and less invasive ‘policing’ and characterization of metastatic breast cancer.
The accurate tracking of cancer and better understanding and exploiting tumor heterogeneity represent major obstacles in more effectively combating this disease. Traditionally, these insights are generated by tissue biopsy but the associated challenges and limitations of this approach have been well described.
Over the past decade a mounting body of research has focused on the promise of liquid biopsy for the detection and analysis of circulating tumor DNA (ctDNA) in blood. This approach is much simpler, less costly and invasive than tissue biopsy, but its capacity to fully capture the entirety of mutations in tumors remains less clear.
“For this reason, the cancer research community is validating its use across tumor types. We are increasingly seeing that liquid biopsy will not replace tissue biopsy per se, but represents a valuable and complementary tool alongside traditional tissue biopsy to more precisely guide clinical decision making,” says Mafalda Oliveira, a Clinical Investigator of VHIO’s Breast Cancer Group led by Cristina Saura, who together with Ana Vivancos, Principal Investigator of our Cancer Genomics Group, are senior authors of the two ASCO 2022 VHIO posters reporting on the utility of liquid biopsy in metastatic breast cancer.
One VHIO-led study, presented by first author Andri Papakonstantinou, an investigator of the Karolinska Institutet’s Department of Oncology-Pathology (Stockholm, Sweden), and an ESMO Translational Research Fellow of VHIO’s Breast Cancer Group headed by Cristina Saura, compared results obtained by liquid biopsy with synchronous tumor biopsy from metastatic breast cancer patients, and analyzed the reliability of ctDNA in detecting and capturing mutations versus traditional biopsy.
“This is one of the largest cohorts of patients in whom liquid biopsy and tissue biopsy have been performed at the same time. Our results indicate that circulating tumor DNA can detect a significant proportion of clinically relevant mutations in metastatic breast cancer,” says Andri Papakonstantinou.
Data also show that tumor subtype, type of gene, and tumor burden measured by radiomics assessment should be integrated with ctDNA results in order to better inform clinical decision making. “We also evaluated factors that can affect the concordance between both approaches for the future selection of those patients who would most likely present said concordance,” concludes Andri Papakonstantinou.
Results of another poster, presented by first author Alberto González, a Post-Doctoral Fellow of VHIO’s the Cancer Genomics Group led by Ana Vivancos, report on the utility of liquid biopsy for identifying emerging mutations and novel treatment options in HR+/HER2- metastatic breast cancer.
The investigators assessed the concordance of detected alterations in two cohorts of patients: one with synchronous sample acquisition by liquid and tissue biopsy, and the other in which results of liquid biopsy were compared with archival tumor samples.
“Plasma analysis could detect the emergence of mutations such as ESR1, PIK3CA and PTEN, but not ERBB2. The trend toward less concordance between plasma sampling and synchronous and archival tissue biopsy is likely due to greater tumor heterogeneity and clonal diversity secondary to systemic treatment,” explains Alberto González.
“Our findings confirm that liquid biopsy provides complementary information regarding tumor tissue that can potentially help to inform treatment decision making,” adds Ana Vivancos.
Both of these posters were prized by GRASP’s (Guiding Researchers and Advocates to Scientific Partnerships) Advocate Choice Award. This patient-led program connects and empowers patients, clinicians and researchers to exchange ideas and learn from each other.
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