The global outbreak of the COVID-19 pandemic forced many cancer societies, including ASCO, to cancel their in-person meetings this year and instead present the latest advancements and new approaches in oncology care via a virtual platform. For the first time in its 56-year history, the ASCO Annual Meeting was presented entirely virtually. Despite the novel format, the meeting was a success, with the diversity of the program and the extraordinary number of new research presented perfectly captured the theme of this year’s meeting “Unite & Conquer: Accelerating Progress Together.”
Lee S. Schwartzberg, MD, FACP, Guest Editor
Throughout this special Conference Highlights issue of The ASCO Post, you’ll find reports from additional clinical trials presented during the virtual program, including data in hematologic cancers and solid tumors. In this introduction I share some thoughts on the studies presented during the Plenary Session of the ASCO20 Virtual Scientific Program.
De Novo Stage IV Breast Cancer
Women presenting with newly diagnosed de novo stage IV breast cancer derived no additional survival benefit from surgery and radiotherapy administered after systemic treatment, although the practice may reduce locoregional progression of disease, results from a randomized phase III trial show.1 The trial conducted by the ECOG-ACRIN Research Group (E2108) included 390 women (median age, 55 years) with de novo stage IV breast cancer. About half of the trial participants had hormone receptor–positive HER2-negative tumors, 29% had HER2-positive tumors, and 10% had triple-negative disease.
An unexpected result of the study was that although there was a 2.5-fold higher risk of local disease progression without locoregional treatment, locoregional treatment for the intact primary tumor did not lead to improved health-related quality of life, as measured by the Functional Assessment of Cancer Therapy—Trial Outcome Index.
Key takeaway: These results will undoubtedly shed some light on the best way to manage the primary tumor when women with breast cancer present with advanced-stage disease, a situation without a lot of quality data to base treatments decisions.
Advanced Urothelial Cancer
The very impressive results from the phase III JAVELIN Bladder 100 trial show maintenance therapy with the checkpoint inhibitor immunotherapy avelumab significantly extended overall survival in patients with advanced urothelial cancer after first-line chemotherapy, and represents the largest survival benefit seen to-date in advanced urothelial cancer in the maintenance setting.2 Although avelumab, which targets PD-1, has been shown to be effective in other metastatic disease settings, this study reports the first data demonstrating efficacy of front-line treatment following initial chemotherapy.
In the study, 700 patients with unresectable locally advanced or metastatic urothelial carcinoma were randomly assigned to receive maintenance avelumab plus best supportive care or best supportive care alone, stratified by best response to first-line chemotherapy, which was gemcitabine with either cisplatin or carboplatin, and were followed for a median of 19.6 and 19.2 months, respectively. When combined with best supportive care, avelumab treatment resulted in a median overall survival of 21.4 months vs 14.3 months for best supportive care alone.
These results are especially significant because while platinum-based chemotherapy is an active first-line regimen for advanced urothelial cancer, progression-free survival and overall survival are generally short because of chemotherapy resistance.
Key takeaway: These results support the use of avelumab as a maintenance treatment following initial chemotherapy.
MSI-H/dMMR Advanced Colorectal Cancer
This is another impressive study presented during the Plenary program that has the potential to change the standard of care in a molecularly defined, poor-prognosis subgroup of patients with advanced colorectal cancer. Interim analysis of the phase III KEYNOTE-177 trial evaluating the efficacy and safety of the PD-1 antibody pembrolizumab vs standard of care chemotherapy with or without bevacizumab or cetuximab as first-line therapy for patients with microsatellite instability–high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer found that pembrolizumab improved progression-free survival by 8.3 months.3 Overall survival results are pending.
Approximately 5% of patients with metastatic colorectal cancer have high microsatellite instability. Previous research suggests that the presence of MSI-H/dMMR tumors in some patients is associated with decreased survival and that these tumors are less responsive to conventional chemotherapy but responded to pembrolizumab in later lines of therapy.
Key takeaway: These data have the potential to change the standard-of-care in first-line therapy for patients with MSI-H/dMMR metastatic colorectal cancer.
Early-Stage EGFR-Positive NSCLC
Osimertinib, a third-generation epidermal growth factor (EGFR) receptor tyrosine kinase inhibitor, was shown to significantly improve disease-free survival compared with placebo in patients with stage IB or IIIA EGFR- mutated non–small cell lung cancer (NSCLC), following surgery and adjuvant chemotherapy, when indicated, according to results from the phase III ADAURA trial.4
Patients with stage II–IIIA NSCLC had an 83% reduction in the risk of disease recurrence or death. The 2-year disease-free survival was 90% with osimertinib vs 44% with placebo in patient with stage II-IIIA NSCLC with an EGFR mutation. In the overall population of patients, stage IB-IIIA, treatment with osimertinib reduce the risk of disease recurrence or death by 79% compared to placebo. Disease-free survival at 2 years with osimertinib was 89% vs 53% with placebo. Overall survival, a secondary endpoint of the study, was immature at the time of data analysis. The safety profile was consistent with the known safety profile of osimertinib.
Key takeaway: This study establishes osimertinib as a new extended adjuvant therapy after surgery and chemotherapy for patients with localized NSCLC with EGFR mutation.
Newly Diagnosed Myeloma
The next-generation proteasome inhibitor carfilzomib plus lenalidomide and dexamethasone (KRd) failed to show superior efficacy in patients with newly diagnosed multiple
myeloma absent a high-risk disease prognosis, compared with the standard-of-care regimen of bortezomib, lenalidomide, and dexamethasone (VRd), results from the randomized phase III ENDURANCE trial showed.5
In the trial, patients were randomly assigned 1:1 to receive VRd or KRd for 36 weeks (induction) and stratified based on intent for transplant at disease progression. After induction treatment, patients were randomly assigned once again in a 1:1 ratio to receive indefinite lenalidomide maintenance vs 2 years. The study found, as of the planned second interim analysis, there were 298 progression-free survival events. Median progression-free survival was 34.4 months for those treated with VRd compared with 34.6 months for KRd. In addition, there was a significantly higher rate of cardio-pulmonary and renal toxicity with KRd, whereas neuropathy rates were higher with VRd.
Key takeaway: Bortezomib, lenalidomide, and dexamethasone remain the standard triplet induction regimen in standard- and intermediate-risk patients with newly diagnosed multiple myeloma.
Disclaimer: Dr. Schwartzberg reported no conflicts of interest.
References
1. Khan SA, et al: A trial of the ECOG Research Group. ASCO20 Virtual Scientific Program. Abstract LBA2.
2. Powles T, et al: JAVELIN Bladder 100 phase III interim analysis. ASCO20 Virtual Scientific Program. Abstract LBA1.
3. Andre T, et al: The phase 3 KEYNOTE-177 study. ASCO20 Virtual Scientific Program. Abstract LBA4.
4. Herbst RS, et al: ADAURA. ASCO20 Virtual Scientific Program. Abstract LBA5.
5. Kumar S, et al: Results of ENDURANCE phase III trial. ASCO20 Virtual Scientific Program. Abstract LBA3.
