Search

Simple Summary: Patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor gene (EGFR) Exon 20 insertion mutations (Exon20ins) used to have poor outcomes after the failure of platinum-based therapies. Amivantamab, a drug that targets two proteins involved in NSCLC (EGFR/MET), was developed and studied in the CHRYSALIS clinical trial. This paper summarizes an analysis comparing outcomes for amivantamab from CHRYSALIS to the outcomes for a mix of treatments that were used in real-world clinical practice (real-world physician's choice [RWPC]). RWPC data were collected from hospitals across Europe in the CATERPILLAR real-world evidence (RWE) study. The outcomes of 114 patients from CHRYSALIS were compared to 55 lines of treatment (LOTs) from CATERPILLAR-RWE, accounting for differences in patient characteristics between the two populations. Overall, the results show that amivantamab was at least twice as good as RWPC for platinum pre-treated patients in terms of tumor response and survival rates. Patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor gene (EGFR) Exon 20 insertions (Exon20ins) at the second line and beyond (2L+) have an unmet need for new treatment. Amivantamab, a bispecific EGFR- and MET-targeted antibody, demonstrated efficacy in this setting in the phase 1b, open-label CHRYSALIS trial (NCT02609776). The primary objective was to compare the efficacy of amivantamab to the choices made by real-world physicians (RWPC) using an external control cohort from the real-world evidence (RWE) chart review study, CATERPILLAR-RWE. Adjustment was conducted to address differences in prognostic variables between cohorts using inverse probability weighting (IPW) and covariate adjustments based on multivariable regression. In total, 114 patients from CHRYSALIS were compared for 55 lines of therapy from CATERPILLAR-RWE. Baseline characteristics were comparable between the amivantamab and IPW-weighted RWPC cohorts. For amivantamab versus RWPC using IPW adjustment, the response rate ratio for the overall response was 2.14 (p = 0.0181), and the progression-free survival (PFS), time-to-next-treatment (TTNT) and overall survival (OS) hazard ratios (HRs) were 0.42 (p < 0.0001), 0.47 (p = 0.0063) and 0.48 (p = 0.0207), respectively. These analyses provide evidence of clinical and statistical benefits across multiple outcomes and adjustment methods, of amivantamab in platinum pre-treated patients with advanced NSCLC harboring EGFR Exon20ins. These results confirm earlier comparisons versus pooled national registry data. [ABSTRACT FROM AUTHOR]

The aim of this paper was to assess the cost-effectiveness of pembrolizumab in first-line for microsatellite-instability-high or mismatch-repair-deficient metastatic colorectal cancer. We have considered the pivotal phase III randomized controlled trial of pembrolizumab in first-line for microsatellite-instability-high mismatch-repair-deficient metastatic colorectal cancer. The last available update of each trial was considered as the original source. Incremental cost-effectiveness ratio was calculated as the ratio between the difference of the costs in the intervention and in the control groups (pharmacy costs) and the difference between the effect in the intervention and in the control groups (progression-free survival). The costs of drugs are at the Pharmacy of the Mater Salutis Hospital of Legnago (VR, Italy) and are expressed in euros (€). Three hundred and seven patients were considered in the pivotal phase III randomized controlled trial. Pembrolizumab obtained a cost per month progression-free survival gained ranged from 6471 € towards mFOLFOX (5-FU, oxaliplatin and leucovorin) plus cetuximab to 7886 € towards mFOLFOX. To sum up, combining pharmacological costs of drugs with the measure of efficacy represented by progression-free survival, at the actual prize pembrolizumab cannot be considered cost-effectiveness for first-line treatment for microsatellite-instability-high mismatch-repair-deficient metastatic colorectal cancer. A reduction in pharmacological costs is mandatory. [ABSTRACT FROM AUTHOR]

Information on Hodgkin lymphoma (HL) is mostly limited to Europe and North America. This real-world, retrospective study assessed treatment pathways and clinical outcomes in adults with stage IIB–IV classical HL receiving frontline treatment (n = 1598) or relapsed/refractory HL (RRHL, n = 426) in regions outside Europe and North America between January 2010 and December 2013. The primary endpoint was progression-free survival (PFS) in the RRHL group. Among patients with RRHL, 89.0% received salvage chemotherapy; most common regimen was etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP; 26.3%). Median PFS in the RRHL group was 13.2 months (95% confidence interval [CI]: 9.9–20.2) and was longer in patients with vs. without stem cell transplantation (SCT; 20.6 vs. 7.5 months; p = 0.0071). This large-scale study identified a lower PFS for RRHL in the rest of the world compared with Europe and North America, highlighting the need for novel targeted therapies and SCT earlier in the treatment continuum. Clinical trial registration: NCT03327571. [ABSTRACT FROM AUTHOR]

Simple Summary : Meningiomas are the most common tumours of the central nervous system (CNS). Despite their benign histology, proximity to critical neurovascular structures may lead to significant morbidity with tumour growth. This is the case for cavernous sinus meningiomas (CSMs), as their growth may surround critical neuro-vascular structures and cause significant morbidity. Radical microsurgical resection carries a high risk of additional neurological deficits, as well as the risk of death. Current management of these tumours, where treatment is indicated, has moved away from radical surgery towards radiotherapy/radiosurgery. This is particularly the case for patients who have residual or recurring tumours after previous surgery. There are many reports that describe the effectiveness of using stereotactic radiosurgery (SRS) for CSMs; however, large cohort analyses are lacking. This multicentre analysis reports the outcome data of over 1000 patients with CSMs who were treated with SRS. SRS shows a high local tumour control rate with few complications. These results agree with previous reports in the literature. SRS is a valuable primary or adjuvant treatment option for CSMs. Cavernous sinus meningiomas (CSMs) remain a surgical challenge due to the intimate involvement of their contained nerves and blood vessels. Stereotactic radiosurgery (SRS) is a safe and effective minimally invasive alternative for the treatment of small- to medium-sized CSMs. Objective: To assess the medium- to long-term outcomes of SRS for CSMs with respect to tumour growth, prevention of further neurological deterioration and improvement of existing neurological deficits. This multicentric study included data from 15 European institutions. We performed a retrospective observational analysis of 1222 consecutive patients harbouring 1272 benign CSMs. All were treated with Gamma Knife stereotactic radiosurgery (SRS). Clinical and imaging data were retrieved from each centre and entered into a common database. All tumours with imaging follow-up of less than 24 months were excluded. Detailed results from 945 meningiomas (86%) were then analysed. Clinical neurological outcomes were available for 1042 patients (85%). Median imaging follow-up was 67 months (mean 73.4, range 24–233). Median tumour volume was 6.2 cc (+/−7), and the median marginal dose was 14 Gy (+/−3). The post-treatment tumour volume decreased in 549 (58.1%), remained stable in 336 (35.6%) and increased in only 60 lesions (6.3%), yielding a local tumour control rate of 93.7%. Only 27 (2.8%) of the 60 enlarging tumours required further treatment. Five- and ten-year actuarial progression-free survival (PFS) rates were 96.7% and 90.1%, respectively. Tumour control rates were higher for women than men (p = 0.0031), and also for solitary sporadic meningiomas (p = 0.0201). There was no statistically significant difference in outcome for imaging-defined meningiomas when compared with histologically proven WHO Grade-I meningiomas (p = 0.1212). Median clinical follow up was 61 months (mean 64, range 6–233). Permanent morbidity occurred in 5.9% of cases at last follow-up. Stereotactic radiosurgery is a safe and effective method for treating benign CSM in the medium term to long term. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the second most lethal cause of cancer-related deaths in Europe. Fragments of tRNAPro are conserved among vertebrates, characterized by pleiotropic regulatory functions and have been found to discriminate colorectal tumors from normal colorectal mucosa. In the current study, we investigated the prognostic utility of 5′-tiRNA-ProTGG levels in CRC. For this purpose, total RNA was extracted from 155 malignant colorectal tumors and 74 adjacent non-cancerous tissue specimens, polyadenylated and reverse-transcribed using an oligo-dT adapter as primer. Real-time quantitative PCR (qPCR) was used to assess the levels of 5′-tiRNA-ProTGG. Kaplan-Meier survival analysis demonstrated that high 5′-tiRNA-ProTGG levels predict both poor disease-free survival (DFS) and overall survival (OS) of CRC patients. Of note, high 5′-tiRNA-ProTGG levels retain their unfavorable prognostic value in patients with rectal cancer and/or moderately differentiated CRC (grade II). More importantly, multivariate cox regression analysis highlighted that the overexpression of 5′-tiRNA-ProTGG constitutes an adverse prognostic factor predicting short-term relapse of CRC patients independently of the established prognosticators in CRC. Finally, bioinformatics analysis unveiled a potentially critical role of 5′-tiRNA-ProTGG regarding the maintenance of cellular homeostasis, signaling, cell communication, and cellular motility. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to further enhance a validated radiomics-based model for predicting pathologic complete response (pCR) after chemo‑radiotherapy in locally advanced rectal cancer (LARC) for use in clinical practice. Methods: A generalized linear model (GLM) to predict pCR in LARC patients previously trained in Europe and validated with an external inter-continental cohort (59 patients), was first examined with further 88 intercontinental patient datasets to assess its reproducibility; then new radiomics and clinical features, and validation methods were investigated to build a new model for enhancing the pCR prediction for patients admitted to our department. The patients were divided into training group (75%) and validation group (25%) according to their demographic. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to reduce the dimensionality of the extracted features of the training group and select the optimal ones; the performance of the reference GLM and enhanced models was compared through the area under curve (AUC) of the receiver operating characteristics. Results: The value of AUC of the reference model was 0.831 (95% CI, 0.701–0.961), and 0.828 (95% CI, 0.700–0.956) in the original and new validation cohorts, respectively, showing a reproducibility in the applicability of the GLM model. Eight features were found to be significant with LASSO and used to establish an enhanced model. The AUC of the enhanced model of 0.926 (95% CI, 0.859–0.993) for training, and 0.926 (95% CI, 0.767–1.00) for the validation group shows better performance than the reference model. Conclusions: The GLM model shows good reproducibility in predicting pCR in LARC; the enhanced model has the potential to improve prediction accuracy and may be a candidate in clinical practice. [ABSTRACT FROM AUTHOR]