MD Anderson Research Highlights for November 30, 2022

Featuring novel immunotherapy and targeted therapy combinations, an evaluation of lung cancer screening criteria, the importance of accurate prognoses for palliative care, and successes of a comprehensive tobacco control effort

The University of Texas MD Anderson Cancer Center’s Research Highlights provides a glimpse into recent basic, translational and clinical cancer research from MD Anderson experts. Current advances include a novel HER2-targeted bispecific antibody for several types of cancers, an immunotherapy and PARP-inhibitor combination that may benefit specific tumor molecular subtypes, a comprehensive look at the efficacy of eligibility criteria for lung cancer screening, the importance of accurate prognoses in palliative rehabilitative care, and a look at the success of MD Anderson’s EndTobacco® Program in reducing the burden of tobacco use in Texas over the last 10 years.

HER2 bispecific antibody shows encouraging early results in HER2-expressing or HER2-amplified cancers  
HER2-targeted therapies are effective in HER2-positive breast and gastric cancers, but their use in other cancers that exhibit HER2 expression or amplification has not been fully explored. In this Phase I study led by Funda Meric-Bernstam, M.D., researchers evaluated the safety and anti-tumor activity of the HER2-targeting bispecific antibody zanidatamab in patients with HER2-expressing or -amplified tumors. Zanidatamab was well tolerated, with the most common side effects being diarrhea and infusion reactions. Among 83 efficacy-evaluable patients with biliary tract, colorectal cancer and other non-breast, non-gastric solid tumors, the treatment resulted in a 37% objective response rate, with antitumor activity seen in 11 different types of cancers. These results highlight zanidatamab’s favorable safety profile and support further evaluation of HER2 as a viable therapeutic target in additional cancer types. Learn more in The Lancet Oncology.

PARP inhibitor plus immunotherapy safe with durable benefit in multiple tumor types with DNA-damage response alterations  
PARP inhibitors are effective in treating patients with tumors containing DNA-damage response (DDR) alterations, such as BRCA1/2-mutant breast cancer. Preclinical data suggest PARP inhibitors work effectively in combination with immune checkpoint inhibitors (ICIs) to enhance antitumor response, but little is known about which patients would benefit from this combination therapy. To evaluate this approach across tumor types, Timothy Yap, M.B.B.S., Ph.D., and colleagues evaluated the safety and efficacy of the PARP inhibitor talazoparib plus avelumab (anti-PD-L1) in two clinical trials. These studies, published in JAMA Oncology, highlight the importance of considering molecular subtype when selecting treatments for future ICI and PARP-inhibitor combination strategies.  

The Phase IIb JAVELIN BRCA/ATM trial evaluated the combination in 200 patients with advanced BRCA1/2d or ATM-altered solid tumors. Patients with BRCA1/2-associated and uterine leiomyosarcoma tumor types had a more durable antitumor response, especially if they had a higher mutational burden. While the treatment was well-tolerated, neither cohort met the target overall response rate of 40%, suggesting that a tumor-agnostic approach is not an efficient strategy for this combination in patients with BRCA1/2-altered tumors. Learn more here.

The Phase Ib/II JAVELIN PARP Medley basket trial enrolled 223 patients with advanced solid tumors in multiple cohorts of different tumor types. The combination therapy achieved overall response rates comparable to PARP and ICI monotherapies, with certain cohorts showing prolonged duration of response. The treatment was well tolerated, with the most common side effects being anemia (33.6%), thrombocytopenia (21.5%), and neutropenia (13.9%). Learn more here.

Study characterizes current state of lung cancer screening 
Lung cancer is the second most common cancer in adults and the leading cause of cancer-related deaths in the U.S., highlighting the importance of early screening and detection. Low dose computed tomography (LDCT) is recommended for screening asymptomatic individuals who meet certain age, smoking pack-years and smoking history eligibility criteria recommended by the U.S. Preventive Services Task Force. Researchers led by Ya Chen Tina Shih, Ph.D., analyzed data from more than 96,000 respondents to categorize those who underwent LDCT screening and to determine whether they met the eligibility criteria. Only 12.8% of eligible individuals underwent LDCT screening. Among screened patients, only 20.9% met all three criteria and 20.1% did not meet any criteria. Of those who did not meet any criteria, the study found factors including a history of stroke or chronic obstructive pulmonary disease were associated with a higher likelihood of screening. This study uncovers possible underuse of LDCT for screen-eligible individuals and overuse in ineligible individuals, suggesting a need to improve the LDCT screening process. Learn more in JAMA Network Open.

Prognosis is key for palliative rehabilitation in an acute inpatient rehabilitation setting
An accurate prognosis is vital for clinical decision-making in patients with cancer undergoing palliative rehabilitation in an acute inpatient setting. To better understand outcomes and associated prognostic factors, researchers led by Jegy Tennison, M.D., performed a secondary analysis of a retrospective study of 163 patients admitted to acute inpatient rehabilitation. They found roughly 1 in 6 patients died within two months of discharge. Patients with early mortality had poorer baseline functional status and were less likely to significantly improve their physical function with an intense, acute inpatient rehabilitation program. Researchers concluded that it would be more appropriate to reassess the prognosis of patients with risk factors for early mortality, which could assist with deciding the appropriate rehabilitation setting and intensity to provide more individualized and meaningful palliative rehabilitation goals. Learn more in The Oncologist.

Comprehensive tobacco control program makes strides in reducing burden of tobacco use in Texas
Tobacco use remains a leading preventable cause of death and disease, responsible for roughly 30% of all cancer-related deaths worldwide and 20% in the U.S. To reduce the burden of tobacco-related cancers in Texas, MD Anderson established the EndTobacco® Program in 2012. The program created evidence-based initiatives and implemented a variety of actions focused on policy, education and tobacco treatment services. In a new study, Jennifer Cofer and colleagues outline their strategy and report the successes of the program since its launch. EndTobacco has educated local and state legislators on tobacco-control measures, provided tobacco treatment education to health professionals, implemented Texas’ only certified tobacco treatment training program and led a statewide initiative to enhance the tobacco-free cultures at institutions of higher education. Between 2014 and 2021, the adult smoking rate in Texas dropped 6%, due in part to state control policies and programs complemented by efforts of the EndTobacco program. Learn more in Cancer Control.