JCO oncology advances最新文献

Purpose: In metastatic breast cancer (MBC), oral capecitabine prescribed at the US Food and Drug Administration (FDA)-approved dose of 1,250 mg/m² twice daily, 14 days on, 7 days off, is associated with poor tolerance. Mathematical models suggest that a fixed-dose (FD), dose-dense schedule may optimize efficacy. We conducted a randomized, open-label trial to compare the efficacy and tolerability of FD capecitabine, 1,500 mg twice daily, 7 days on, 7 days off (FD-7/7), with the FDA-approved dose and schedule (standard-dose [SD]-14/7).

Methods: Females with MBC and any previous lines of therapy were included. Patients were randomly assigned 1:1 to either FD-7/7 or SD-14/7. The primary end point was 3-month progression-free survival (PFS). Capecitabine-related toxicities were graded at each visit.

Results: Between October 2015 and April 2021, 153 patients were enrolled (n = 80 FD-7/7, n = 73 SD-14/7). The 3-month PFS was 63.1% (95% CI, 52.0 to 74.2) in the FD-7/7 arm and 67.2% (95% CI, 54.5 to 79.9) in the SD-14/7 arm. Restricted mean survival time was used to report estimates of effect. The PFS (restricted mean) at 33 months was 10.1 months (95% CI, 7.6 to 12.6) in the FD-7/7 arm compared with 9.1 months (95% CI, 6.6 to 11.7) in the SD-14/7 arm. The overall survival (restricted mean) at 80 months was 30.6 months (95% CI, 23.6 to 37.6) in the FD-7/7 arm versus 24.5 months (95% CI, 18 to 31.1) in the SD-14/7 arm. Toxicity-related treatment discontinuation occurred in 24 patients (32.9%) in the SD-14/7 arm compared with seven patients (8.8%) in the FD-7/7 arm (P = .0002). Grade 2 to 4 toxicities occurred in 79.5% in the SD-14/7 arm compared with 37.5% in the FD-7/7 arm (P < .0001).

Conclusion: In MBC, FD capecitabine 1,500 mg twice daily on a 7/7 schedule has less toxicity and similar efficacy when compared with body surface area-based dosing on a 14/7 schedule.

Purpose: Recent data suggest that the rate of burnout among oncologists has risen over time. In addition to the negative effect of burnout on individuals, widespread burnout may prevent the oncology workforce from meeting patient care needs.

Methods: ASCO surveyed US-based oncologists in patient care roles about their professional well-being and satisfaction and the effect of both on their career plans. Burnout was assessed using measures of emotional exhaustion and depersonalization from the Maslach Burnout Inventory Human Services Survey. Data from the 2023 survey were compared with data from Shanafelt et al (JCO, 2014) collected about oncologist burnout/well-being in 2013.

Results: In all, 328 responses to the 2023 survey were analyzed. Burnout was significantly higher compared with 2013, 45% in 2013 versus 59% in 2023 (P < .01). In 2023, <25% of oncologists reported feeling satisfied with their work-life integration, compared with nearly 35% in 2013 (P < .01). Burnout was significantly associated with being a caregiver in one's personal life, being under age 50 years, and working more than 60 hours per week (all P < .05). Over 20% of respondents reported that it was likely or definite that they would reduce their clinical hours in the next 12 months. Additional practice/administrative support and reducing work hours were identified as potential solutions to improve job satisfaction.

Conclusion: Oncologists in 2023 are experiencing higher rates of burnout compared with a decade ago. System-based interventions to reduce burnout are necessary to maintaining an adequate workforce to provide care for current and future patients with cancer.

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths with a 5-year survival rate of 13%. Surgical resection remains the only curative option as systemic therapies offer limited benefit. Poor response to chemotherapy and immunotherapy is due, in part, to the dense stroma and heterogeneous tumor microenvironment (TME). Opportunities to target the PDAC stroma may increase the effectiveness of existing or novel therapies. Current strategies targeting the stromal compartment within the PDAC TME primarily focus on degrading extracellular matrix or inhibiting stromal cell activity, angiogenesis, or hypoxic responses. In addition, extensive work has attempted to use immune targeting strategies to improve clinical outcomes. Preclinically, these strategies show promise, especially with the ability to alter the tumor ecosystem; however, when translated to the clinic, most of these trials have failed to improve overall patient outcomes. In this review, we catalog the heterogenous elements of the TME and discuss the potential of combination therapies that target the heterogeneity observed in the TME between patients and how molecular stratification could improve responses to targeted and combination therapies.

Purpose: A phase II/III trial is a type of phase III trial that has embedded in it an intermediate phase II go/no-go decision as to whether to continue the accrual to the phase III sample size. We examine the design characteristics and experience of a well-defined set of National Cancer Institute phase II/III trials, with special emphasis on designed accrual suspensions while awaiting the data to become mature enough for the phase II analysis. This experience is used to highlight the potential of using a calendar backstop to avoid an inordinately long accrual suspension.

Methods: We identified all phase II/III trials conducted by NRG Oncology or its precursor National Cancer Institute Cooperative Groups (Radiation Therapy Oncology Group, Gynecologic Oncology Group, and National Surgical Adjuvant Breast and Bowel Project). The design characteristics were recorded, and, for completed trials, the trial results in terms of sample sizes and timing of analyses were tabulated.

Results: Twenty-two trials were identified, 14 of which had a time-to-event end point for their phase II component. Thirteen of these 14 trials had designed accrual suspensions. Seven of the eight completed trials had designed accrual suspensions, all of which went on longer than their projected suspension times (3-20 months longer than planned). The trade-offs for using a backstop are discussed using one of these trials as an example.

Conclusion: Phase II/III trials with an accrual suspension and a predefined backstop for the phase II analysis can be a useful tool for minimizing patient exposure to ineffective experimental treatments while still obtaining the trial results in a timely fashion.

Purpose: The increasing use of dietary supplements by patients with cancer and other chronic diseases requires the systematized review of potential interactions between prescription drugs and nutrients from supplements by health care and clinical research teams. Dietary supplement interaction databases are positioned to fill a gap in quantifying potential risks for patients, although none have been assessed for reliability in data interpretation. The NatMed database, a source for comprehensive reports on mechanistic and safety data for dietary supplement ingredients, was evaluated for use in future investigations.

Methods: Data from NatMed were retrieved using licensed end points for ingredient monographs with drug-nutrient interactions with doxorubicin across five pharmacokinetic and metabolic pathways, and for ingredient monographs with antioxidant activity. Interactions between dietary supplements and doxorubicin treatment and antioxidant monographs were independently reviewed and characterized by clinical pharmacists. Cohen's K was used to measure interrater reliability and the degree of agreement between pharmacists.

Results: Three hundred fifteen potential interactions with doxorubicin (n = 115 monographs) and 455 other antioxidant ingredients were identified and reviewed by clinical pharmacists. There was substantial to near-perfect agreement for drug-nutrient interactions with doxorubicin (Cohen's K = 0.64-0.85) and for antioxidants (Cohen's K = 0.84). A small proportion of retrieved monographs were not validated by the clinical pharmacists for interactions with doxorubicin (n = 20 occurrences, 6.4%) or for antioxidant activity (n = 28, 6.2%).

Conclusion: A high degree of reliability in data on dietary supplement interactions with doxorubicin and mechanisms of action suggests NatMed may be a dependable source of data for future investigators. Additional procedures including independent data validation and use of multiple dietary supplement interaction databases will strengthen the quality of findings in future studies.

Purpose: In the United States, there are disparities in access to care for patients with non-small cell lung cancer (NSCLC) on the basis of socioeconomic and racial/ethnic factors. This study investigates the association between race/ethnicity and the utilization of immune checkpoint inhibitor (ICI) therapy among older patients with advanced NSCLC (aNSCLC).

Methods: This retrospective study used data from the SEER-Medicare-linked database. The cohort included patients (age 66 years or older) diagnosed with aNSCLC (stage III/IV) between March 2015 and December 2017, and they were followed through December 2019. Race/ethnicity was categorized as non-Hispanic (NH)-White, NH-Black, Hispanic, and Other. ICI therapy utilization was determined by identifying any usage of ICI agents (nivolumab, pembrolizumab, atezolizumab, durvalumab, ipilimumab, and cemiplimab-rwlc) from the Medicare database. Multivariable logistic regression models assessed the association between race/ethnicity and ICI therapy utilization (yes, no). Effect measure modification analyses were conducted by sex, socioeconomic status, and comorbidity.

Results: The final sample included 26,836 patients; 76.2% were NH-White, 10.1% NH-Black, 5.7% Hispanic, and 8.0% Other. The overall ICI therapy utilization proportion was 17.8%, varying across ethnicities: NH-Black 14.1%, Hispanic 16.3%, NH-White 18.4%, and Other 18.5%. In comparison with NH-White patients, NH-Black patients were 15% less likely to receive ICI therapy (adjusted odds ratio, 0.85 [95% CI, 0.75 to 0.96]). Furthermore, the association between race/ethnicity and utilization of ICI therapy was modified by comorbidity status, sex, and socioeconomic status.

Conclusion: NH-Black patients with aNSCLC were less likely to receive ICI therapy than their NH-White counterparts. Our findings indicate the racial/ethnic disparities in ICI therapy utilization and call for further interventions to optimize access to care.