Publications & Abstracts
Academic Thoracic Oncology Medical Investigators Consortium (ATOMIC)
Prospective Observational Study Revealing Early Pulmonary Function Changes Associated With Brigatinib Initiation
Symptomatic early onset pulmonary events (EOPEs) were observed in 3% to 6% of patients within 1 week of starting brigatinib at 90 mg daily for 7 days followed by 180 mg daily.
We conducted a prospective observational cohort study to measure pulmonary function changes on initiating brigatinib.
Used by permission: Terry L. Ng, MD – 2020 International Association for the Study of Lung Cancer.
Published by Elsevier Inc. All rights reserved. ISSN: 1556-0864
The Activity Of Brigatinib In Patients With Disease Progression After Second Generation Anaplastic Lymphoma Tyrosine Kinase Inhibitors And An Exploratory Analysis Of Circulating Tumor DNA
Brigatinib, a second generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), is central nervous system (CNS) penetrant and active against anaplastic lymphoma kinase (ALK) resistance mutations.
We prospectively studied the activity of brigatinib in patients with disease progression after second generation ALK TKIs.
- Brigatinib demonstrated activity in patients with disease progression after second-generation anaplastic lymphoma (ALK) tyrosine kinase inhibitors (TKI’s).
- The objective response was similar in patients who received second generation ALK inhibitors as first-line or second line therapy, and patients with and without brain metastases at baseline.
- Circulating tumor DNA testing (ctDNA) for ALK resistance mutations is feasible; however, a number of patients did not have detectable ctDNA or an ALK resistance mutations.
Used by permission: Thomas E. Stinchcombe, MD – Duke Cancer Institute
Academic GI Cancer Consortium (AGICC)
Phase II study of selumetinib (AZD6244, ARRY-142886) plus irinotecan as second-line therapy in patients with K-RAS mutated colorectal cancer
More than half of colorectal tumors harbor activating mutations in RAS/RAF proteins. Selumetinib (AZD6244, ARRY-142886) is a small molecule kinase inhibitor targeting MEK kinase, downstream of RAS. We examined the efficacy and safety of selumetinib with irinotecan in second-line therapy.
Patients with K-RAS mutated colorectal cancer, progressing on first-line oxaliplatin‐based chemotherapy with bevacizumab, were eligible for this multicenter openlabel phase I/II trial. In part A, a dose was determined using a standard “3 + 3” design; in part B, efficacy was determined. The primary endpoint was RECIST response rate. Historical data for irinotecan were used as reference. Secondary endpoints included progression-free survival and overall survival.
Used by permission: Howard Hochster MD, Yale University
Academic Breast Cancer Consortium (ABRCC)
Phase IB/II Open-Label Single Arm Study to Evaluate Safety and Efficacy of Tucatinib in Combination with Letrozole and Palbociclib in Subjects with Hormone Receptor Positive and HER2 Positive Metastatic Breast Cancer (TULiP Trial)
Breast cancers overexpressing HER2-oncogene and hormone receptors (HR) represent therapeutic challenge because of a bi-directional cross-talk between HR and HER2 pathways leading to tumor progression and drug resistance [1, 2]. In preclinical experiments, HER2-targeted agents combined with endocrine therapy showed synergy in suppressing the growth of HR+/HER2+ tumors [2, 3]. Several phase III clinical trials combining anti-hormonal and HER2-targeted agents have been performed [4, 5]. However, these trials were not practice changing because no overall survival benefits were demonstrated. Therefore, there is a strong rationale for evaluation of novel targeted drug combinations in HR+/HER2+ breast cancer subtype.
Used by permission: Elena Shagisultanova MD, PhD – University of Colorado Cancer Center
Academic Myeloma Cancer Consortium (AMyC)
Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma
This is the first clinical trial to investigate CPD in multiple myeloma.
- Results suggest that the regimen is a well-tolerated and highly active combination for patients with relapsed/refractory multiple myeloma.
Used by permission: Jatin J. Shah MD – MD Anderson Cancer Center, Houston TX
Safety and Efficacy of Carfilzomib in Patients with Previously-Treated Systemic Light-Chain (AL) Amyloidosis
- Plasma cells producing amyloidogenic light chains are highly sensitive to proteasome inhibition1
- Bortezomib has high response rates in relapsed AL amyloidosis2
- Carfilzomib is a novel, irreversible proteasome inhibitor active in multiple myeloma, with less neurotoxicity3
- The safety and efficacy of carfilzomib in patients with AL is not known
Used by permission: Adam D. Cohen, MD – University of Pennsylvania