The Annual Meeting of the American Society of Clinical Oncology (ASCO), now in its 56th year, took place under a new virtual format on 29–31 May 2020. Opening the meeting, ASCO President Howard A. “Skip” Burris III highlighted that although COVID-19 had changed the format of this year’s ASCO 2020, the collective determination to make progress against cancer was as strong as ever.
ASCO President Howard A. “Skip” Burris III
Dr Burris explained that the COVID-19 pandemic has changed the way patients with cancer receive care and has encouraged healthcare professionals in the oncology community and their patients to weigh the risks and benefits of delaying treatment.
Dr Burris highlighted that data on how COVID-19 was impacting patients was being collected through the new ASCO Registry and CancerLinQ database, which this year crossed a milestone of 2.5 million patients.
As ever, this year’s ASCO meeting aimed to enable clinicians to understand how and when to integrate novel research into patient care. Dr Burris noted that the galvanising theme of the ASCO20 Virtual Scientific Program – “Unite and Conquer: Accelerating Progress Together” – would take on even more resonance given the extraordinary times as ASCO’s global audience learnt about new developments in cancer care.
“The world is grappling with a pandemic and we are all readjusting to a new reality, but it cannot stop us. We, the ASCO Community, are absolutely unwilling to let anything stop us in the fight against cancer.”
Howard A. “Skip” Burris III, ASCO President
Breast Cancer, Local/Regional, Adjuvant Breast Cancer
Nadia Harbeck, Brustzentrum der Universität München, Munich, Germany, presented data from the Phase III KAITLIN study which showed that adjuvant treatment with trastuzumab emtansine (T-DM1) does not improve outcomes or reduce toxicity relative to that with a taxane plus trastuzumab in patients with HER2+ early breast cancer (Abstract 500; NCT01966471). However, 3-year invasive disease-free survival (DFS) rates of 93–94% after a median follow-up of
57 months achieved with both treatments could still be considered an ‘excellent’ result in this high-risk population. In addition, a significant 29% lower risk for deterioration in global health status was reported from the start of HER2 targeted therapy with T-DM1 compared with a taxane plus trastuzumab, which the researchers attributed to taxane use.
The standard-of-care for HER2-positive (HER2+) early breast cancer is chemotherapy plus one year of HER2-directed therapy. However, recurrence – particularly in high-risk populations – remains a problem, as does systemic chemotherapy-associated toxicity.
“Adjuvant trastuzumab plus pertuzumab plus chemotherapy remains the standard-of-care for patients with high-risk HER2 positive early breast cancer.”
Nadia Harbeck, Brustzentrum der Universität München, Munich, Germany
Anna van der Voort, Netherlands Cancer Institute, Amsterdam, Netherlands, presented long-term follow-up data of the Phase III TRAIN-2 study which showed that patients with stage II-III HER2+ breast cancer who received neoadjuvant chemotherapy and dual HER2-blockade derived no survival benefit from the addition of anthracyclines (Abstract 501; NCT01996267). Following a median follow-up of 48.8 months, a pathologic complete response rate of 68% was reported for patients treated with neoadjuvant chemotherapy (paclitaxel and carboplatin). This did not significantly differ from the rate of 67% reported for those patients who received three cycles of the anthracycline-containing regimen of 5-fluorouracil, epirubicin and cyclophosphamide followed by six cycles of paclitaxel and carboplatin. The use of anthracyclines increased the risk of:
Triple-negative breast cancer (TNBC) has a relatively high relapse rate and poor outcome after standard therapy among all subtypes of breast cancer. Data from the Phase III SYSUCC-001 study (Abstract 507; NCT01112826) presented by XI Wang, Sun Yat-Sen University Cancer Center, Guangzhou, China, demonstrated that maintenance therapy with metronomic capecitabine for one year following standard treatment was well-tolerated and significantly improved DFS versus observation in patients with operable TNBC. Five-year DFS was significantly better in the capecitabine group than in the observation group (83% vs. 73%, respectively), although 5-year overall survival (OS) was not significantly different between the two groups (85% vs. 81%, respectively).
Long-term results from the large Phase III Microarray In Node negative Disease may Avoid ChemoTherapy (MINDACT) study, testing the 70-gene signature MammaPrint, confirmed its utility as a decision-making tool for the use of adjuvant chemotherapy in patients with breast cancer according to Fatima Cardoso, Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal (Abstract 506; NCT00433589). These follow-up data highlighted that the primary distant metastasis-free survival (DMFS) endpoint previously reported at 5 years continued to be met in chemotherapy untreated clinical-high/genomic-low risk women, confirming MINDACT as a positive de-escalation study. While more distant relapses were noted in those patients not receiving chemotherapy, these were deemed to be in line with the ‘natural history’ of luminal breast cancer and the estimated gain of 2.6% DMFS with chemotherapy was deemed to be small given its harmful effects.
5-year DFS in the capecitabine versus observation group
Metastatic Breast Cancer
Approximately 6% of newly diagnosed patients with breast cancer present with stage IV disease and an intact primary tumour (IPT). Although retrospective studies have previously suggested that the use of locoregional treatment (LRT) for IPTs may improve prognosis, these studies typically enrolled younger women who had smaller tumours, oestrogen receptor-positive disease and a lower metastatic burden. Seema Ahsan Khan, Northwestern Memorial Hospital, Chicago, USA, presented data from a Phase III study of the Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network (ECOG-ACRIN) Research Group (E2108). This study demonstrated that early initiation of LRT of an IPT in women with de novo stage IV metastatic breast cancer does not appear to prolong survival or improve health-related quality of life compared with systemic therapy alone (Abstract LBA2; NCT01242800). Patients had previously completed 16 or more weeks of treatment with optimal systemic therapy (OST), which was based on the patients’ tumour biologic profile as well as age and menopausal status. After a median follow-up of 59 months, the 3-year OS rates for OST plus LRT and OST alone were 68.4% and 67.9%, respectively. Of note, there were no differences between the two treatment groups with regard to OS among women with an HER2+ tumour subtype or a hormone receptor-positive and HER2-negative tumour subtype.
“Randomised studies have previously provided conflicting survival benefits of locoregional treatment in women with metastatic breast cancer and an intact primary tumour.”
Seema Ahsan Khan, Northwestern Memorial Hospital, Chicago, USA
Pembrolizumab monotherapy has previously shown promising antitumour activity and a manageable safety profile in patients with metastatic TNBC in the KEYNOTE-012, -086 and -119 studies. Javier Cortes, IOB Institute of Oncology, Madrid and Barcelona, Spain, presented data from KEYNOTE-355 which demonstrated that pembrolizumab combined with chemotherapy (taxane or gemcitabine/carboplatin) had a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus chemotherapy alone in patients with previously untreated locally recurrent inoperable or metastatic TNBC whose tumours expressed programmed cell death ligand 1 (PD-L1; Combined Positive Score ≥10 [Abstract 1000; NCT02819518]). OS follow-up is ongoing. The combination of pembrolizumab and chemotherapy was also generally well-tolerated.
CNS PFS duration with tucatinib versus placebo in patients with HER2+ breast cancer and brain metastases
Breast cancer has the second highest incidence of brain metastasis among all cancers, with the risk and incidence of brain metastases varying by breast cancer subtype. Data from the HER2CLIMB study demonstrated that tucatinib, a selective HER2 kinase inhibitor, had a survival benefit in patients with HER2+ breast cancer and brain metastases when added to trastuzumab and capecitabine according to Nancy U. Lin, Dana-Farber Cancer Institute, Boston, USA (Abstract 1005; NCT02614794). This data analysis focused on 291 participants from the original HER2CLIMB study population, all of whom had brain metastases at baseline. Those patients randomly allocated to receive tucatinib achieved a significant 68% reduction in central nervous system (CNS) PFS compared with those patients who received placebo, with a CNS PFS duration of 9.9 versus 4.2 months, respectively. In addition, tucatinib-treated patients had a 42% reduced risk for death, with a median OS of 18.1 versus 12.0 months for patients receiving placebo, respectively.
Risk factors for brain metastases in patients with HER2+ metastatic breast cancer
In response to the COVID-19 pandemic, ASCO completely reimagined and reinvented its 2020 Annual Meeting by delivering a successful virtual meeting. This virtual platform still had the aim of achieving an engaging and educational meeting experience for participants from around the world. Delegates were able to view data, clinical experiences, patient perspectives and best practices that will hopefully stimulate new ways of thinking and ultimately translate into optimal patient care within the oncology field.
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