New research was virtually presented at AACR 2020, the American Association for Cancer Research Annual Meeting, from April 27-28. The features below highlight some of the studies that emerged from the conference.
Cancer Ups COVID-19 Vulnerability
With prior research indicating that patients with cancer are generally more vulnerable to infections, study investigators felt systematic analysis of diverse cohorts of patients with cancer affected by COVID-19 were needed. The team performed a multi-center study of patients with confirmed COVID-19 infection, 105 of whom had cancer and 536 of whom were age-matched patients without cancer (controls). Patients with cancer had significantly higher risks of mortality (odds ratio [OR], 2.34), ICU admission (OR, 2.84), severe or critical symptoms (OR, 2.79), and invasive mechanical ventilation (OR, 2.71) when compared with controls. While overall mortality rates were 11.4% for those with cancer and about 5% for those without, patients with hematologic malignancies, lung tumors, and esophageal tumors had mortality rates of 33.3%, 18.1%, and 16.7%, respectively. Patients with early-stage cancers had outcomes similar to those without cancer, but those with metastatic disease had ORs of 5.58 for death, 6.59 for ICU admission, 5.97 for severe symptoms, and 55.42 for invasive ventilation.
Treatment Holiday Worsens PFS in BRAF-Mutant Melanoma
Although previous studies suggest objective responses with BRAF and MEK inhibitors in the majority of patients with BRAF-mutant melanoma, data also suggest that acquired resistance limits response durations with these drugs. Preclinical data suggest that intermittent dosing of these agents may delay such resistance. To determine whether intermittent dosing of BRAF/MEK inhibitors improved progression-free survival (PFS) in patients with advance BRAF-mutant melanoma when compared with continuous dosing, researchers randomized patients on 8-weeks of continuous BRAF/MEK inhibitor therapy to either further continuous therapy or intermittent dosing on a 3-week-off, 5-week-on schedule. Median PFS was statistically significantly longer (9 months from randomization) with continuous dosing when compared with intermittent dosing (5.5 months). At a median follow-up of 2 years, median overall survival was 29.2 months in both groups. In the continuous treatment group, 77% of patients discontinued treatment due to disease progression, compared with 84% in the intermittent treatment group.
Pre-existing ESR1 Mutations Predict Endocrine Therapy Failure & Poor Survival
Despite research suggesting that mutation in ESR1 is an acquired mechanism of resistance to endocrine therapy (ET), the impact of this mutation on therapy response in primary breast cancer remains unclear. To better understand this impact, study investigators analyzed more than 3,200 real-world and population-based early-stage primary breast cancers. Tissues sampled from initial diagnosis, prior to any treatment, were analyzed for the presence of ESR1 mutations using RNA sequencing. ESR1 resistance mutations were identified in 0.9% of cases, of which 1.1% were estrogen receptor-positive. In estrogen receptor-positive disease, presence of ESR1 mutation was significantly associated with poor relapse-free (RFS) and overall survival (OS), and it predicted poor RFS and OS within the patient group who received ET. “We confirm for the first time that such early mutations predict eventual resistance to standard hormone therapy in the adjuvant setting,” write the study authors.
The Socioecological Context of Tobacco & Vape Shop Locations
Evidence suggests that, despite increased public health efforts to discourage teens from using hazardous tobacco products, use of electronic nicotine delivery systems (ENDS) remains high, due in part to direct youth targeting by tobacco and vaping companies, with many ENDS containing fruit and candy flavors that are particularly attractive to youth in products with high nicotine levels. For a study, researchers analyzed national/local nicotine product use in youth by gender, age, and racial/ethnic group; explored the socio-ecological context of tobacco/vape shops via geospatial mapping; and conducted an environmental scan of social media platforms combined with Google and Yellow Pages searches. Ever use of e-cigarettes was reported by 13.5% of middle schoolers and 37.7% of high schoolers. The location of tobacco and vape shops appeared to correspond with areas with higher percentages of ethnic minorities, regardless of average income. However, lower-income cities tended to have more of these shops when compared with very high-income cities. Even after adjusting for store type, tobacco products cost less in neighborhoods with lower median household incomes and in those with a higher proportion of Hispanic residents. The study authors suggest that population-based tobacco (including vaping) prevention and control strategies in coordination with the FDA are critical to reducing use and initiation of these products among all Americans, particularly ethnic minorities and youth.
Tumor Immune Biology Differs Between Metastatic & Early TNBC
Although research has linked pre-existing intratumoral immune response—characterized by presence of tumor-infiltrating lymphocytes or cytotoxic effector T cells—with improve prognosis in early triple-negative breast cancer (eTNBC) but suggest that immune-rich tumors are not prognostic in metastatic TNBC (mTNBC), whether the T-cell immune biology has differential prognosis between eTNBC and mTNBC remains unclear, as different immune biomarkers were used across studies to make these observations. For a study, researchers evaluated the prognostic value of the T effector RNA gene signature (Teff), across two eTNBC and two mTNBC clinical studies using the same biomarker methodology. Although Teff levels were similar within the eTNBC studies and within the mTNBC studies, Teff score was significantly higher in the eTNBC studies. Among baseline prognostic characteristics assessed, lymph node involvement in the eTNBC studies was the only one associated with Teff. Multivariate analysis found elevated Teff to be associated with improved overall survival in two eTNBC studies but to have no prognostic value in two mTNBC trials. Similar results were seen at various Teff cutoffs.