Quality of life in the adjuvant setting: A meta-analysis of US Food and Drug Administration approved anti-cancer drugs from 2018 to 2022.

BACKGROUND: In oncology, quality of life (QoL) questionnaires were historically designed to be used in the advanced or metastatic setting. We sought to determine the effects of contemporary treatments on QoL in the adjuvant setting and to determine if the QoL instruments used in these studies provide a relevant assessment. METHODS: We conducted a systematic identification of all anti-cancer drugs used in the adjuvant setting and approved by the US Food and Drug Administration from January 2018 to March 2022. We conducted a quality evaluation and a meta-analysis of reported QoL results. We used the global QoL results when multiple QoL outcomes were reported. RESULTS: There were 224 FDA approvals reviewed, of which 12 met the inclusion criteria. The placebo was the control arm in 10 out of 12 trials. Of those, 11 trials (92 %) assessed QoL, and ten (83 %) reported results. In reports with QoL results, a moderate-risk of bias was found in 3 out of 10 (30 %) and a high-risk of bias in 6 out of 10 (60 %) of reports, respectively. No trial reported a meaningful difference between arms. The meta-analysis found an overall detrimental effect on QoL in the experimental arm, though it was not statistically different. CONCLUSION: This study identified 12 FDA registration trials in the adjuvant setting between 2018 and 2022. We found a moderate- to high-risk of bias in 90 % of the ten trials reporting QoL data. Our meta-analysis suggested a detrimental effect on QoL in the experimental arm, questioning the relevancy, in the adjuvant setting, of thresholds that were mostly developed in the advanced or metastatic setting. POLICY SUMMARY: Future works should focus on specificities of the adjuvant setting when considering QoL evaluation.

Predictors of long-term durable response in de novo HER2-positive metastatic breast cancer and the real-world treatment experience at two institutions.

PURPOSE: HER2-directed therapies enable some patients with de novo HER2+ metastatic breast cancer (MBC) to achieve long-term, durable responses (DR). Expert opinion dictates indefinite HER2-directed therapies for patients who achieve DRs, but real-world examples of this practice are lacking in the literature. Patient factors that predict DR continue to be elucidated. METHODS: This is a retrospective study of patients with de novo HER2 + MBC. DR is defined as absence of progression/death at any point after diagnosis. Controls are patients with evidence of progression/death. Age, ER/PR status, sites of metastasis, surgical resection of primary tumor, and initial treatment were analyzed. RESULTS: 96 patients with de novo HER2 + MBC, 28 with DR, and 68 with progression were identified. 75% of patients with DR had a single metastatic site, compared with 47% of patients with progression (OR 3.7, p = 0.01). 64% of patients with DR received a regimen containing trastuzumab, pertuzumab, and a taxane, while 28% of patients who progressed did (OR 4.5, p < 0.001). 57% of patients with DR underwent surgical removal of breast primary, compared with 24% of patients who progressed (OR 4.3, p = 0.002.) Among patients with DR, nine patients have been receiving trastuzumab for over ten years with no evidence of disease and one patient opted to discontinue trastuzumab. CONCLUSION: Nearly a third of patients with de novo HER2 + MBC achieved DR. Factors that correlate with DR include single metastatic site, initial trastuzumab, pertuzumab and taxane therapy, and surgical resection of primary tumor. Among patients with DR, indefinite trastuzumab administration is the norm.

Insights on recent innovations in bladder cancer immunotherapy.

Bladder carcinoma is the most common genitourinary cancer, with a high prevalence and global incidence. In addition to early detection by cytology, the management of bladder cancer has recently advanced, not only by improvements in conventional treatments such as surgery and chemotherapy, but also through the introduction of immunotherapeutic strategies. The number of approved immunotherapeutic agents has dramatically increased, with various preclinical and clinical applications in cancer drug discovery. Some bladder cancer immunotherapies include immune checkpoint inhibitors, adoptive cell therapy, cytokine-based therapy, bispecific antibodies, and antibody-drug conjugates. This review provides an overview of some of the innovative immunotherapeutic agents approved and in development that can potentially be used in the treatment of bladder cancer.

National Trends in End-of-Life Care for Veterans With Advanced Cancer in the Veterans Health Administration: 2009 to 2016.

PURPOSE: It is imperative to provide quality end-of-life (EOL) care for patients with cancer. Although rates of hospice use within the Veterans Health Administration have improved, antineoplastic administration and intensive care unit (ICU) admission at the EOL, indicators of aggressive care, have not clearly declined over recent years. METHODS: We identified 32,665 veterans diagnosed with stage IV lung, colorectal, or pancreatic cancer who died between 2009 and 2016 using a novel EOL Dashboard Tool created from Veterans Administration Cancer Registry data. This EOL tool reports the incidence of antineoplastic drug use in the last 14 days of life, ICU admission in the last 30 days of life, and hospice admission or consult. Change from 2009 to 2016 was assessed using a repeated measures one-way analysis of variance with post hoc test for linear trend of time for individual cancers and two-way analysis of variance for all cancers combined. RESULTS: Antineoplastic use in the last 14 days of life declined from 6.8% in 2009 to 4.4% in 2016 (P = .03). ICU admission in the last 30 days did not change significantly, from 13.3% in 2009 to 14.7% in 2016. The exception was patients with stage IV lung cancer, in whom ICU admissions increased from 12.9% to 16.2% (P = .01). Patients using hospice services increased from 32.4% to 52.6% (P < .01). CONCLUSION: Although antineoplastic administration at the EOL is declining for veterans with stage IV cancer, ICU admissions are unchanged and becoming more common in stage IV lung cancer despite increasing hospice use.

Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma.

Despite extensive genetic diversity of HIV-1 in chronic infection, a single or few maternal virus variants become the founders of an infant's infection. These transmitted/founder (T/F) variants are of particular interest, as a maternal or infant HIV vaccine should raise envelope (Env) specific IgG responses capable of blocking this group of viruses. However, the maternal or infant factors that contribute to selection of infant T/F viruses are not well understood. In this study, we amplified HIV-1 env genes by single genome amplification from 16 mother-infant transmitting pairs from the U.S. pre-antiretroviral era Women Infant Transmission Study (WITS). Infant T/F and representative maternal non-transmitted Env variants from plasma were identified and used to generate pseudoviruses for paired maternal plasma neutralization sensitivity analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma. Yet, all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies and variably sensitive to heterologous plasma neutralizing antibodies. Also, these infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants (p = 0.012). Altogether, our findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could further reduce infant HIV-1 infection risk.