BREAST CANCER

Clinical outcomes and immune markers by race in a phase I/II clinical trial of durvalumab concomitant with neoadjuvant chemotherapy in early-stage TNBC

A recent study found that treatment outcomes were similar among Black and non-Black triple-negative breast cancer patients who received neoadjuvant durvalumab in combination with chemotherapy (Clin Cancer Res 2022;28(17):3720-3728). To better understand the safety and efficacy of this therapeutic approach for this patient population by race, the study authors enrolled additional Black patients to a Phase I/II clinical trial. The study population included 67 patients and the primary efficacy endpoint was pathologic complete response (pCR). Of these participants, 21 (31%) identified as Black, which brings the proportion of Black patients closer to that of the local community. Forty patients identified as non-Hispanic White, three as Hispanic/Latino, and three as Asian. There was no significant difference between patient characteristics and baseline tumor features by race. Among the 67 patients enrolled in the trial, 31 (46%) had a pCR to neoadjuvant durvalumab plus chemotherapy, according to the study authors. They reported no statistically significant differences by race. Forty-three percent of Black patients had a pCR compared with 48 percent of non-Black patients. There was also no statistically significant differences between Black and non-Black patients for the rates of metastatic recurrence (14% vs. 17%), 3-year overall survival (81% vs. 87%), and 3-year event-free survival (71.4% vs. 78.3%). Patients in both the Black and non-Black groups with a pCR had significantly longer event-free survival and overall survival than those who did not, study findings showed. No significant difference in PD-L1 status or adverse events were observed by race. "Pathologic complete response rates, 3-year OS, and EFS after neoadjuvant immunotherapy and chemotherapy were similar in African-American and non-African-American patients," the study authors concluded. "Toxicities, including the frequency of irAEs, were also similar."

AUTHOR COMMENTARY: "Our study demonstrates that, if patients are given similar treatment and similar follow-up, the differences in outcomes between Black and non-Black patients are reduced," explained Lajos Pusztai, MD, DPhil, Professor of Medicine at Yale University and Director of Breast Cancer Translational Research and Co-Director of the Cancer Center Genomics, Genetics, and Epigenetics Program. "By improving health care access and delivery, we could mitigate some of the health care disparities that exist in our society."

SOLID TUMORS

Pan-cancer efficacy of pralsetinib in patients with RET fusion-positive solid tumors from the phase I/II ARROW trial

Pralsetinib-a highly selective RET inhibitor-was well-tolerated and demonstrated robust, durable responses in patients with RET fusion-positive cancers regardless of tumor type, according to recent findings from the Phase I/II ARROW trial (Nat Med 2022;28(8):1640-1645). The study enrolled 29 patients with 12 different RET fusion-positive solid tumor types-excluding non-small cell lung cancer and thyroid cancer-who had previously received or were not candidates for standard therapies. Of these patients, 23 were able to be evaluated for efficacy. The median age was 53 years, 14 (61%) were female, 65 percent were White, 30 percent Asian, and 4 percent Black. The majority of patients had metastatic disease (87%) and received prior therapies for their cancer (87%). The researchers reported that three patients (13%) had a confirmed complete response and 10 (43%) had a confirmed partial response. The data revealed a median duration of response of 11.7 months, as well as median progression-free and median overall survival of 7.4 month and 13.6 months, respectively. The study authors observed treatment-related side effects in 25 patients (86%). Twenty patients (69%) experienced Grade 3 or higher adverse events. Seventeen patients (59%) had short-term dose interruptions and 13 (45%) had permanent dose reductions due to side effects. "These data validate RET as a tissue-agnostic target with sensitivity to RET inhibition, indicating pralsetinib's potential as a well-tolerated treatment option with rapid, robust, and durable anti-tumor activity in patients with diverse RET fusion-positive solid tumors," the study authors concluded.

AUTHOR COMMENTARY: "We've had an explosion in clinical next-generation sequencing that allows us to understand shared biomarkers across multiple tumor types, and this study was important to determine if RET fusions are actionable across cancer types," said study author Vivek Subbiah, MD, Associate Professor of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center. "We observed responses regardless of tumor type, prior therapy, or gene fusion partner. These data validate RET as a tissue-agnostic target with sensitivity to RET inhibition."

EARLY-ONSET CANCERS

Is early-onset cancer an emerging global epidemic? Current evidence and future implications

A recent study showed that the incidence of early-onset cancers (those diagnosed before age 50), including cancers of the breast, colon, esophagus, kidney, liver, and pancreas, among others, has dramatically increased worldwide, beginning around 1990 (Nat Rev Clin Oncol 2022; doi:10.1038/s41571-022-00672-8). To better understand the reasons behind this trend, researchers analyzed global data describing the incidence of 14 different cancer types that showed increased incidence in adults before age 50 from 2000 to 2012. The team then searched for available studies that examined trends of possible risk factors, including early life exposures in the general populations. Lastly, they examined the literature describing clinical and biological tumor characteristics of early-onset cancers compared to later-onset cancers diagnosed after age 50. The study authors found that the early life exposome-which includes diet, lifestyle, weight, environmental exposures, and microbiome-has changed significantly in the last several decades. They hypothesized that factors such as westernized diet and lifestyle may be contributing to this epidemic of early-onset cancer. They acknowledged that this increased incidence may be due, in part, to early detection through screening programs. The effects of individual exposures remain largely unknown, according to the study authors, who noted that "to study early-life exposures and their implications for multiple cancer types will require prospective cohort studies with dedicated biobanking and data-collection technologies. Raising awareness among both the public and health care professionals will also be critical."

AUTHOR COMMENTARY: "Without such studies, it's difficult to identify what someone having cancer now did decades ago or when one was a child," said Tomotaka Ugai, MD, PhD, a research scientist in the Department of Pathology at Brigham and Women's Hospital. "Because of this challenge, we aim to run more longitudinal cohort studies in the future where we follow the same cohort of participants over the course of their lives, collecting health data, potentially from electronic health records, and biospecimens at set time points. This is not only more cost-effective considering the many cancer types needed to be studied, but I believe it will yield us more accurate insights into cancer risk for generations to come."