Search

A novel antibody–drug conjugate, trastuzumab deruxtecan is a combination of a human epidermal growth factor receptor 2 (HER2)-targeting antibody and DNA topoisomerase I inhibitor used to treat HER2-low/positive advanced breast cancer. To determine its safety and efficacy in treating HER2-low/positive advanced breast cancer, we performed a meta-analysis of several randomized clinical trials (RCTs) including DESTINY-Breast02 (NCT03523585), DESTINY-Breast03 (NCT03529110), and DESTINY-Breast04 (NCT03734029). We searched PubMed, Embase, and the Cochrane Library for RCTs on the efficacy and safety of trastuzumab deruxtecan that were published before May 2023. The efficacy endpoints included median progressive-free survival (PFS), overall survival (OS), duration of response (DOR), overall response rate (ORR), and clinical benefit rate (CBR). The safety endpoints included treatment-related adverse events. Statistical analyses were performed using RevMan 5.4 software. To ensure transparency, this study was registered on the International Prospective Register of Systematic Reviews website (CRD42023414170). Three RCTs involving 1689 patients were included. Compared with physician-recommended and conventional treatments, trastuzumab deruxtecan exhibited statistically significant improvements in PFS, ORR, and CBR. The median OS and DOR failed to be combined; however, the analyzed studies showed that they were longer. The incidence of adverse events was generally higher with trastuzumab deruxtecan than with physician-recommended or conventional treatments. The results of this study suggest that trastuzumab deruxtecan is more effective in treating HER2-low/positive advanced breast cancer than physician-recommended or conventional treatments. However, trastuzumab deruxtecan-related adverse drug reactions should be closely monitored because of its higher incidence of adverse events. • HER2-targeted therapy is ineffective in locally advanced or metastatic disease. • Trastuzumab deruxtecan may improve function compared to traditional treatments. • We included 1689 breast cancer patients from three randomized clinical studies. • Verification of trastuzumab deruxtecan's efficacy and safety is needed. [ABSTRACT FROM AUTHOR]

Background In cancer randomized controlled trials (RCT), alternative endpoints are increasingly being used in place of overall survival (OS) to reduce sample size, duration and cost of trials. It is necessary to ensure that these endpoints are valid surrogates for OS. Our aim was to identify meta-analyses that evaluated surrogate endpoints for OS and assess the strength of evidence for each meta-analysis (MA). Materials and methods We performed a systematic review to identify MA of cancer RCTs assessing surrogate endpoints for OS. We evaluated the strength of the association between the endpoints based on (i) the German Institute of Quality and Efficiency in Health Care guidelines and (ii) the Biomarker-Surrogate Evaluation Schema. Results Fifty-three publications reported on 164 MA, with heterogeneous statistical methods Disease-free survival (DFS) and progression-free survival (PFS) showed good surrogacy properties for OS in colorectal, lung and head and neck cancers. DFS was highly correlated to OS in gastric cancer. Conclusion(s) The statistical methodology used to evaluate surrogate endpoints requires consistency in order to facilitate the accurate interpretation of the results. Despite the limited number of clinical settings with validated surrogate endpoints for OS, there is evidence of good surrogacy for DFS and PFS in tumor types that account for a large proportion of cancer cases. [ABSTRACT FROM AUTHOR]

The present review gives an overview of systematic reviews published in peer reviewed Journals analysing quality of reporting in oncology studies. PUBMED and Cochrane library were searched to identify systematic reviews assessing quality of reporting for randomized controlled trials (RCTs) and observational studies (OBS). Recommendations and primary endpoints used to assess the quality of reporting were described. Intrinsic quality of reporting was analyzed using an Overall Quality Score for literature Reviews (OQSR). Main evaluation themes were overall quality of reporting (20/58) and reporting of Health-Related Quality Of Life (HRQOL) in RCTs (7/58). Reporting recommendations used were not detailed in 56.9% of reviews. Insufficient reporting for the methodological description (randomization, blinding details, and allocation concealment) and the rationale for using specific measure of HRQOL were highlighted. OQSR was significantly higher for reviews published between 2010 and 2014 (after the PRISMA Publication), as compared to those published between 1996–2009 (median OQSR 10 (10–11) versus median OQSR 9 (6–10) respectively, p = 0.0053). Intrinsic quality of reporting is satisfactory and has been improved in the last years. [ABSTRACT FROM AUTHOR]

Outcomes for breast cancer patients with residual disease (RD) after neoadjuvant chemotherapy (NACT) and HER2-targeted therapy may be better than anticipated leading to a smaller absolute benefit of adjuvant trastuzumab emtansine (T-DM1). Therefore, accurate estimates of 3-year disease-free survival (DFS) can aid in treatment planning. We reviewed randomized trials of NACT and HER2-targeted therapy in breast cancer (excluding T-DM1) and calculated mean 3-year DFS weighted by study sample size. Meta-regression comprising linear regression weighted by sample size (mixed-effects) was performed to explore associations between 3-year DFS and year of accrual and trial-level patient, disease, and treatment factors. Data were reported quantitatively irrespective of statistical significance. Eleven studies (N = 3581) were included in the primary analysis. The mean 3-year DFS for patients with RD was 79.7% (95% CI 77.4–80.9). This was higher for trials completing accrual after 2010 [83% (95% CI 79.3–86.3)] and for those receiving dual HER2 targeted therapy [83.4% (95% CI 79.2–87.7]. Better outcomes for ER positivity, later accrual and dual Her-2 targeted therapy were confirmed in meta-regression. Negative quantitative significance was observed for larger clinical tumor size and nodal involvement. The 3-year DFS for patients with RD has improved over time possibly due to dual HER2 targeted therapy. This will reduce the absolute benefit of adjuvant T-DM1 in this group of patients. • Some patients with HER2 + breast cancer and residual disease (RD) after neoadjuvant therapy have good outcomes. • The absolute benefit of adjuvant T-DM1 in these low-risk patients is unclear. • Data from trials of neoadjuvant therapy was pooled to calculate a weighted mean 3-year DFS. • 3-year DFS for non-pCR was 79.7% compared to 77% reported in control arm of the KATHERINE trial. • 3-year DFS improved over time possibly due to use of dual HER2 targeted therapy. [ABSTRACT FROM AUTHOR]

Improving quality of life is a key issue for patients with prostate cancer (PCa). Lifestyle interventions could positively impact the quality of life of patients. However, there is no clear-cut understanding of the role of diet, exercise and risky behaviour reduction in improving the quality of life of men with PCa. The aim of this review was to systematically summarize randomized controlled trials on lifestyle in PCa patients with quality of life as main outcome. 17 trials were included. Most of them referred to exercise interventions (71%) and involved men undergoing androgen deprivation therapy (47%). Exercise studies yielded the greater amount of positive results on quality of life outcomes (67%), followed by dietary interventions (50%) and combined lifestyle interventions (33%). In particular, supervised exercise programs with resistance training sessions were the ones producing greater convincing evidence for benefits on quality of life. Further studies with high methodological quality providing adequate information to develop evidence-based, personalized lifestyle interventions that can effectively ameliorate PCa-related quality of life are needed. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fatigue is a prevalent and disruptive symptom for many cancer survivors. • Mindfulness-based interventions (MBIs) have been tested to reduce fatigue in cancer. • Meta-analyses tested the efficacy of MBIs in cancer for fatigue and vigor/vitality. • MBIs significantly improved fatigue and vigor/vitality compared to controls. • Evidence grade was low due to risk of bias, heterogeneity, and publication bias. This systematic review and meta-analysis was designed to determine the efficacy of mindfulness-based interventions (MBIs) in improving fatigue-related outcomes in adult cancer survivors. Randomized controlled trials (RCTs) were identified from PubMed, MEDLINE, PsycINFO, CINAHL, Web of Science, and EMBASE databases and reference lists of included studies. Separate random-effects meta-analyses were conducted for fatigue and vitality/vigor. Twenty-three studies reporting on 21 RCTs (N = 2239) met inclusion criteria. MBIs significantly reduced fatigue compared to controls at post-intervention (g = 0.60, 95 % CI [0.36, 0.83]) and first follow-up (g = 0.42, 95 % CI [0.20, 0.64]). Likewise, MBIs significantly improved vitality/vigor at post-intervention (g = 0.39, 95 % CI [0.25, 0.52]) and first follow-up (g = 0.35, 95 % CI [0.03, 0.67]). The evidence grade was low due to risk of bias, substantial heterogeneity, and publication bias among studies. MBIs show promise in improving fatigue and vitality/vigor in cancer survivors. More rigorous trials are needed to address current gaps in the evidence base. [ABSTRACT FROM AUTHOR]

• Treatment options for prostate cancer (PC) have greatly expanded in the last years. • Despite improvements in diagnosis and treatment options, PC remains one of the most frequent causes of mortality in men. • The cyclin-dependent kinases (CDK) pathway has a fundamental role for carcinogenesis. • CDK-inhibitors are novel agents representing a promising treatment approach in PC. • Several trials are evaluating the role of these agents in different stages of PC. The rapidly expanding scenario of treatment options for patients affected by prostate cancer (PC) is leading to improved outcomes; however, PC still represents one of the most frequent causes of male mortality. Thus, while translational research is trying to unravel the molecular landscape underlying carcinogenesis, disease progression and treatment resistance, several clinical trials are evaluating novel options to further expand therapeutic options. The cyclin-dependent kinases (CDK)-pathway represents a promising therapeutic target for different cancer types; due to the pivotal role of this pathway in the regulation of PC cell cycle, three CDK4/6-inhibitors (abemaciclib, palbociclib and ribociclib) are currently being investigated in several clinical trials. In this paper, we review the current knowledge on CDK-pathway and the mechanism of action of CDK-inhibitors; we discuss the biological rationale for their use in PC and the state of the art of clinical trials focused on the demonstration of their potential role in early or advanced stage, in hormone-sensitive and castration-resistant state. Finally, the potential application of precision oncology for treatment selection in PC is discussed. [ABSTRACT FROM AUTHOR]

Spin, the misrepresentation of research findings, in clinical trial abstract has been shown to influence how oncologist rate a drug's efficacy. We searched PubMed for clinical trials published in ten key journals in 2017. Our primary objectives were to assess the frequency and manifestations of spin in the abstracts of those clinical trials that measured both overall survival and at least one surrogate efficacy endpoints. 124 trials were included for analysis. We found evidence of spin in 46 of 124 (37.1%, 95% CI 29.1%–45.9%) trial abstracts. Spin in the abstract results was most often due to authors emphasizing a statistically significant subgroup analysis (n = 6). Spin in the abstract conclusions was most often due to authors relying on a statistically significant surrogate endpoint to highlight the bioefficacy of the intervention (n = 17). Spin is prevalent in the abstracts of oncology clinical trials that measure OS and a surrogate endpoint. The conclusion sections of abstracts were most prone to contain spin. When OS was the primary endpoint, spin was primarily used to distract from the nonsignificant OS data. To mitigate unintentional hype for cancer therapies, we recommend authors structure their conclusions around patient-important outcomes. [ABSTRACT FROM AUTHOR]