Publications & Abstracts
Academic Thoracic Oncology Medical Investigators Consortium (ATOMIC)
A Multicenter Retrospective Chart Review of Clinical Outcomes Among Patients With KRAS G12C Mutant Non–Small Cell Lung Cancer
Oncogenic mutations in KRAS occur in approximately 26% and 11% of patients with lung adenocarcinoma in Western and Asian populations, respectively. 1-3 Until recently, there has been no licensed therapeutic targeting KRAS in patients with non–small cell lung cancer (NSCLC). That changed on May 28, 2021, when the United States Food and Drug Administration (FDA) granted accel- erated approval to sotorasib for second-line or later treatment of patients with locally advanced or metastatic KRAS G12C mutant NSCLC. This was the first FDA-approved targeted therapy for patients with KRAS mutant NSCLC, and it was based on a single-arm study demonstrating a promising objective response rate (37.1%), with a median duration of response of 11.1 months and median progression-free survival (PFS) of 6.8 months 4 among patients predominantly treated in the third line or later. There is a paucity of real-world data describing clinical outcomes in patients with locally advanced or metastatic KRAS G12C mutated NSCLC in the second-line or later, as most prior studies featured outcomes in the first line setting, evaluated specific patient subgroups, or evaluated the prognostic vs. predictive value of KRAS G12C compared to non-G12C genotypes. We sought to compile a large, academic medical center-based historical dataset to clarify clinical outcomes in the second line or later among patients with KRAS G12C mutant NSCLC.
Used by permission: Wade Iams, MD, Vanderbilt Ingram Cancer Center
Treatment Patterns and Outcomes in ALK or ROS1 altered NSCLC: An ATOMIC Registry Study
- New tyrosine kinase inhibitors (TKIs) targeting ALK and ROS1 have emerged over the last decade.
- Data on long term outcomes, sequential therapies, and development of brain metastases are limited.
- Identify treatment patterns in ALK+ and ROS1+ NSCLC
- Evaluate effect of 1st TKI on development of brain metastases
- Estimate overall survival (OS) in ALK+ and ROS1+ NSCLC
Used by permission: Melina Marmarelis, MD, University of Pennsylvania
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, The Ottawa Hospital
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)
A durable complete response to ceritinib in a patient with ROS1-mutated, early-onset metastatic colon cancer
For many years colorectal cancer (CRC) has been one of the leading causes of cancer-related mortality worldwide and is currently the third-leading cause of death among all cancers in the United States. In 2020, the estimated number of new cases of colorectal cancer nationwide is 104,610, while the number of deaths it causes is projected to exceed 50,000. While the overall incidence has been declining in recent decades, the incidence of CRC in patients under the age of 50 years has been steadily increasing since the 1980’s, at a rate of about 2% per year.
Used by permission: Christopher Lieu, MD, University of Colorado Cancer Center
A Phase II Study Investigating Cabozantinib in Patients with Refractory Metastatic Colorectal Cancer (AGICC 17CRC01)
Multi-tyrosine kinase inhibitors have shown clinical activity in metastatic colorectal cancer patients. Cabozantinib, a multi-tyrosine kinase inhibitor, exhibited potent antitumor activity superior to regorafenib in preclinical colorectal cancer patient-derived tumor xenograft models. This Phase II study aimed to investigate cabozantinib, a multityrosine kinase inhibitor, in refractory, metastatic colorectal cancer patients.
Used by permission: Aaron Scott, MD, University of Arizona & Wells Messersmith, MD, University of Colorado, Denver
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)
The phase IB/II clinical trial NCT03054363 tested targeted combination of HER2 inhibitor tucatinib, anti-hormonal agent letrozole and CDK4/6 inhibitor palbociclib in HR+/HER2+ metastatic breast cancer (MBC). Results showed tolerability and anti-tumor activity of this regimen in heavily pretreated patients (pts) with HR+/HER2+ disease. Here we report an exploratory analysis of intracranial efficacy in enrolled patients with central nervous system metastases (CNS MTS).
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
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