Reopened Trial: Jennifer Eads, MD on Study EA2174 for Esophageal and Gastroesophageal CancerDecember 14, 2020
From the Co-Chairs, November/December 2020December 14, 2020
EA8191 – Phase III Study of PET-Directed Local or Systemic Therapy Intensification in Prostate Cancer Patients with Post-Prostatectomy Biochemical Recurrence
Currently, there is significant variability in the use, nature, and timing of radiation and systemic therapies for patients with post-prostatectomy biochemical recurrence. Furthermore, the available treatments yield high rates of second recurrence. Despite the advent of molecular imaging and consequent improvements in disease detection, no prospective data exist to demonstrate that these advances lead to better outcomes.
This study proposes that PET scan–based treatment intensification—with either enhanced systemic therapy or with metastasis-directed radiation for cytoreduction—will improve progression-free survival relative to non-tailored, standard therapy. The trial aims to show the clinical significance, if any, of findings seen on PET imaging but not on conventional imaging. The results may help determine if therapeutic intensification strategies based solely on PET findings are safe and warranted.
EA9181 – A Phase III Randomized Trial of Steroids +Tyrosine Kinase Inhibitor Induction with Chemotherapy or Blinatumomab for Newly Diagnosed BCR-ABL-positive Acute Lymphoblastic Leukemia in Adults
The EA9181 trial challenges the traditional paradigm of therapy in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Patients will receive either the standard treatment of chemotherapy, steroids, and a tyrosine kinase inhibitor (TKI) or blinatumomab, steroids, and a TKI. Blinatumomab is a bispecific T-cell engager antibody with FDA approval to treat refractory or relapsed B-lineage ALL.
Investigators expect that by using the latter combination and closely monitoring for the achievement of a molecular response, as measured by minimal residual disease (MRD), they may be able to limit the use of cytotoxic chemotherapy required for central nervous system prophylaxis. The combination of blinatumomab, steroids, and a TKI may also increase the rate and duration of MRD negativity, leading to improved long-term remission and survival.
EA2176 – A Randomized Phase III Study of Immune Checkpoint Inhibition with Chemotherapy in Patients with Treatment-Naïve Metastatic Anal Cancer
EA2176 is the first randomized phase III clinical trial ever to be conducted in patients with advanced cancer of the anal canal. Approximately 90% of this type of cancer is squamous cell carcinoma, which is associated with a human papillomavirus (HPV) infection. EA2176 is for this patient population. The study will determine if adding the immunotherapy nivolumab to standard chemotherapy will improve progression-free survival.
EA2176 builds on the recently published findings of the worldwide InterAACT trial, which established the combination of carboplatin and paclitaxel as the standard initial chemotherapy treatment for inoperable anal cancer. The new study represents the next step for patients; investigators hope the addition of immunotherapy to standard chemotherapy will extend progression-free survival.
EA5182 – Randomized Phase III Study of Combination AZD9291 (osimertinib) and Bevacizumab versus AZD9291 (osimertinib) Alone as First-Line Treatment for Patients with Metastatic EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)
Patients with metastatic EGFR-mutant lung cancers receive EGFR tyrosine kinase inhibitors (TKIs) as first-line treatment because multiple studies confirmed superiority over cytotoxic chemotherapy. Recently, the drug osimertinib demonstrated improved progression-free survival in this setting compared to other agents, leading to its FDA approval and positioning as the preferred first-line single-agent EGFR TKI. Nonetheless, osimertinib is only effective for a finite period, and limited choices exist upon progression outside of chemotherapy-based approaches.
Other trials have shown that the addition of bevacizumab to EGFR TKI therapy improves progression-free survival. Thus, the combination of osimertinib and bevacizumab compared to single-agent osimertinib may prolong progression-free survival, delay the need for systemic chemotherapy, and possibly culminate in an overall survival benefit. EA5182 aims to explore this; if successful, the results could meaningfully improve outcomes for patients with metastatic EGFR-mutant lung cancers.
EAA181 – Effective Quadruplet Utilization After Treatment Evaluation (EQUATE): A Randomized Phase III Trial for Newly Diagnosed Multiple Myeloma Not Intended for Early Autologous Transplantation
The purpose of this study is to establish if minimum residual disease (MRD) can help identify which patients may benefit from consolidation treatment with the quadruplet bortezomib, daratumumab, lenalidomide, and dexamethasone. It will compare this regimen to standard triplet daratumumab, lenalidomide, and dexamethasone. Other studies suggest that the four-drug regimen is effective, but investigators do not know if all patients benefit from it or it only helps those with MRD.
The primary objective of EQUATE is to assess if the quadruplet yields superior overall survival compared to the triplet in MRD-positive patients; secondary objectives include conducting the same assessment in MRD-negative patients, and evaluating progression-free survival in both MRD positive and MRD-negative patients.