Carboplatin, nab-paclitaxel plus atezolizumab in Impower 130 trial: New weapons beyond controversies

Letter to edito

Prognostic Factors of Survival for High-Grade Neuroendocrine Neoplasia of the Bladder: A SEER Database Analysis

Background: High-grade neuroendocrine carcinoma (NEC) is a rare and aggressive variant of bladder cancer. Considering its rarity, its therapeutic management is challenging and not standardized. Methods: We analyzed data extracted from the Surveillance, Epidemiology, and End Results (SEER) registry to evaluate prognostic factors for high-grade NEC of the bladder. Results: We extracted data on 1134 patients: 77.6% were small cell NEC, 14.6% were NEC, 5.5% were mixed neuro-endocrine non-neuroendocrine neoplasia, and 2.3% were large cell NEC. The stage at diagnosis was localized for 45% of patients, lymph nodal disease (N+M0) for 9.2% of patients, and metastatic disease for 26.1% of patients. The median overall survival (OS) was 12 months. Multivariate analysis detected that factors associated with worse OS were age being >72 years old (HR 1.94), lymph nodal involvement (HR 2.01), metastatic disease (HR 2.04), and the size of the primary tumor being >44.5 mm (HR 1.80). In the N0M0 populations, the size of the primary tumor being <44.5 mm, age being <72 years old, and major surgery were independently associated with a lower risk of death. In the N+M0 group, the size of the primary lesion was the only factor to retain an association with OS. Conclusions: Our SEER database analysis evidenced prognostic factors for high-grade NEC of the bladder that are of pivotal relevance to guide treatment and the decision-making process

Bone Targeting Agents in Patients with Prostate Cancer: General Toxicities and Osteonecrosis of the Jaw

Introduction: Bone metastases are the most frequent site of secondary localization of prostate cancer (PCa) and are present in about 90% of cases of advanced disease. Consequently, an ade-quate management of bone involvement is of pivotal importance in the therapeutic approach and skeletal-related events (SREs) need to be closely monitored and promptly assessed and treated. Bone targeting agents (BTAs), consisting in bisphosphonates and denosumab, are an essential part of the treatment of metastatic prostate cancer that accompanies systemic treatments throughout the most part of the history of the disease. Activity and safety of bone targeting agents: These treatments are correlated to better outcomes in terms of reduction of SREs and, in metastatic castration resistant setting, of increased overall survival (OS), but several important adverse events have to be managed and prevented. Of these, osteonecrosis of the jaw (ONJ) is extremely invalidating and should be managed with a special attention. Discussion: The role of BTAs in prostate cancer is pivotal throughout many stages of the disease, but several toxicities should be quickly recognized and treated. We aim at recollecting evidence on clinical benefit of BTAs, common and specific toxicities, and explore the pathophysiology and clinical aspects of osteonecrosis of the jaw. We present a review of the literature to report the role of the different types of bone targeting agents in the management of prostate cancer with bone metastases with a particular focus on common toxicities and ONJ to rec-ollect current evidences on the activity of these compounds and the correct management of their adverse events

Adjuvant PD-1 and PD-L1 Inhibitors and Relapse-Free Survival in Cancer Patients: The MOUSEION-04 Study

Background: Adjuvant treatment has always been a cornerstone in the therapeutic approach of many cancers, considering its role in reducing the risk of relapse and, in some cases, increasing overall survival. Adjuvant immune checkpoint inhibitors have been tested in different malignancies. Methods: We performed a meta-analysis aimed to explore the impact of adjuvant PD-1 and PD-L1 inhibitors on relapse-free survival (RFS) in cancer patients enrolled in randomized controlled clinical trials. We retrieved all phase III trials published from 15 June 2008 to 15 May 2022, evaluating PD-1/PD-L1 inhibitors monotherapy as an adjuvant treatment by searching on EMBASE, Cochrane Library, and PubMed/ Medline, and international oncological meetings’ abstracts. The outcome of interest was RFS. We also performed subgroup analyses focused on age and gender. Results: Overall, 8 studies, involving more than 6000 patients, were included in the analysis. The pooled results highlighted that the use of adjuvant PD-1/PD-L1 inhibitors may reduce the risk of relapse compared to control treatments (hazard ratio, 0.72; 95% confidence intervals, 0.67–0.78). In addition, the subgroup analyses observed that this benefit was consistent in different patient populations, including male, female, younger, and older patients. Conclusions: Adjuvant anti-PD-1/PD-L1 treatment is associated with an increased RFS in the overall population and in subgroups divided according to age and gender

Treatment Options for Metastatic Urothelial Carcinoma After First-Line Chemotherapy

Urothelial carcinoma (UC) is a frequently diagnosed tumor and an important cause of cancer deaths worldwide. Until a few years ago, despite the unquestioned role of platinum-based chemotherapy, therapeutic choices beyond the first line were limited and related to unsatisfactory outcomes. Metastatic UC has always been associated with a poor prognosis, with overall survival only slightly above a year. In the recent past, huge progress has been made in our understanding of the molecular and genomic disease characteristics, to enable stratification of patients in terms of prognosis and treatment responses. Unfortunately, we still do not have the perfect combination of clinical biomarkers to tailor the optimal treatment for each patient, despite making several efforts in this direction. The therapeutic arsenal has been augmented by immune checkpoint inhibitors (ICIs), which nowadays represent the backbone of the second-line setting. Equally revolutionary was the FDA’s approval of erdafitinib, a potent fibroblast growth factor receptor (FGFR) inhibitor, the use of which is reserved for patients whose tumor harbors specific FGF pathway alterations. Recently, the therapeutic landscape of metastatic UC has been enhanced by the introduction of novel compounds, consisting of antibody–drug conjugates (ADCs). Enfortumab vedotin is an antibody targeting nectin-4, a cell adhesion molecule highly expressed in UC, conjugated to monomethyl auristatin E (MMAE), a microtubule-disrupting agent. Sacituzumab govitecan is a humanized monoclonal antibody targeting Trop-2, a transmembrane glycoprotein, conjugated to the active metabolite of irinotecan. These two compounds have received accelerated approval by the FDA in patients pretreated with platinum-based chemotherapy and immunotherapy. Several ongoing trials are investigating the role of ICIs combined with chemotherapy, antiangiogenic drugs, or other ICIs, as well as the efficacy of PARP inhibitors and target therapies, hoping to provide information for some important unmet needs. In this review, we aim to evaluate the current potential treatment options after first-line chemotherapy

Cardiac Toxicity From Afatinib in EGFR-Mutated NSCLC: A Rare But Possible Side Effect

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Hyperammonemic encephalopathy during XELOX regimen. Is it capecitabine or oxaliplatin responsible?

Hyperammonemic encephalopathy represents a rare adverse effect of several chemotherapeutic agents, occurring in about 0.7% of patients treated with fluoropyrimidines, and it is independent from dihydropyrimidine dehydrogenase deficiency. Instead, its physiopathology is linked to the inhibition of Krebs cycle by fluoroacetate, leading to decreased ATP production, and to the inhibition of the urea cycle. Oxaliplatin seems to induce hyperammonemic encephalopathy in a similar way, acting on mitochondria. Here, we report the intriguing case of acute hyperammonemic encephalopathy in a 65-year-old patient with preserved liver function, who was treated with oxaliplatin and capecitabine for a metastatic, G1, atypical lung carcinoid. We reviewed the literature and found very few reports of oxaliplatin or capecitabineinduced hyperammonemic encephalopathy. Out of five cases of capecitabine-related hyperammonemic encephalopathy analyzed (four plus our case), median time to hyperammonemic encephalopathy onset was 6 days, with median serum ammonia levels of 213 \u3bcmol/L. Oxaliplatin-related hyperammonemic encephalopathy analyzed cases were three (two plus ours), with a median time to hyperammonemic encephalopathy of 11 days and median serum ammonia levels of 167 \u3bcmol/L. Identified predisposing factors for chemotherapy-induced hyperammonemia, such as dehydration, liver and renal impairment, infections, and sarcopenia were absent in our case. We hypothesize that the combination of a platinum-derivative and a fluoropyrimidine multiplies the risk of hyperammonemic encephalopathy, even in the absence of predisposing factors nor impaired liver function. We therefore suggest to always consider the risk of hyperammonemia when starting fluoropyrimidinesbased chemotherapy, especially combined with platinumderivatives, and to timely investigate neurologic symptoms monitoring ammonia serum levels. Anti-Cancer Drugs 31: 1103-1105

Guiding treatment selection with immunotherapy compared to targeted therapy agents in patients with metastatic kidney cancer

Introduction: Kidney cancer treatment has been first revolutionized by the advent of targeted therapies (TKIs and mTOR inhibitors) and then by the approval of immunotherapy and immunocombinations. Whereas immunocombinations represent the most used first-line therapy in intermediate/poor risk patients with clear-cell tumors, cabozantinib and nivolumab are both effective compounds at progression, and till today it is not totally clear what to prefer. No standard treatments are approved in post-second-line setting and in non-clear carcinoma. Areas covered: The aim of this review is to summarize the main evidence supporting the use of targeted therapies and immunotherapy, in every setting of clear-cell and non-clear cell renal cell carcinoma, while also providing an insight into promising ongoing and upcoming trials. Expert opinion: We speculate on what could help physicians in guiding the therapeutic decision-making process in advanced kidney cancer. International mRCC Database Consortium criteria are still recommended for the choice of primary treatments, despite presenting several limitations in the current immunotherapy-era. Multiple predictors of response to immunotherapy or targeted therapies are emerging but validated biomarkers are awaited. Furthermore, we discuss therapeutic sequences in kidney cancer, guessing how physicians may prefer immunotherapy or TKI as later-line strategies on the basis of previous treatments

Has breast cancer in the elderly remained the same over recent decades? A comparison of two groups of patients 70years or older treated for breast cancer twenty years apart.

OBJECTIVES: Breast cancer (BC) in the elderly population is by far the most frequent malignancy in Western countries; however, little evidence is available regarding the specific management of this group. The purpose of this study was to identify how the biological and clinical characteristics of cancer have changed over the past 20years by comparing two groups of elderly patients with breast cancer operated on 20years apart. The secondary endpoint was to underline potential changes in surgical strategy over the past 20years. MATERIALS AND METHODS: One group of consecutive elderly patients undergoing surgery for BC between January 1990 and December 1993 (Group A), and one group undergoing surgery between January 2008 and December 2011 (Group B) were identified and analyzed. Data regarding surgical treatment, stage, tumor grading, hormonal and HER2/neu receptors, and Ki-67 were collected and compared. RESULTS: A total of 422 elderly patients underwent surgical treatment, 142 in Group A and 280 in Group B. An earlier stage at presentation was detected in Group B, T1 (57.5% B vs. 31.6% A) and N0 (64.6% B vs. 54.2% A). Surgical treatment in the first group was more extensive while conservative procedures were more frequently performed in the second group. Despite the earlier presentation, tumor grade was higher in Group B (G3 10.6% A vs. 32.1% B, p<0.05). Overexpression of Ki-67 was again more frequent in Group B (56.2% B vs. 32.5% A, p<0.05). Hormonal and HER2/neu receptor expression was comparable. CONCLUSIONS: Nowadays, elderly patients with BC are more likely to present at an early stage; therefore, conservative surgery is a feasible option. Despite potential bias related to changes of pathology and immunohistochemistry examination techniques over the decades, the biological characteristics of recent patients with BC seem to be consistent with more aggressive tumors. Tailored treatment should be offered with regard to biological age, the cancer-specific profile and active life expectancy

Single-agent carboplatin in extensive disease small-cell lung cancer patient with liver failure: A case report within the experience of a single institution

Until recently, platinum-based chemotherapy has represented the benchmark for the treatment of extensive disease small-cell lung cancer (ED-SCLC). ED-SCLC patients are often diagnosed with poor performance status (PS ≥2) and/or compromised organ functions. In fact, up to 63% of ED-SCLC has extensive liver involvement at diagnosis, which correlates with a poor prognosis. Whether to treat patients with tumor-related organ failure is still debated and the selection of those who could benefit from chemotherapy is crucial. Moreover, severe liver impairment contraindicates the administration of etoposide. Among 74 consecutive ED-SCLC patients followed at our institution from January 2017 to November 2019, three patients received single-agent carboplatin as a first-line treatment due to liver failure. We provide a brief description of a former heavy smoker 70-year-old man who was diagnosed with ED-SCLC and severe liver involvement leading to liver failure. The patient received a first-line treatment with single-agent carboplatin, obtaining a partial response, clinical benefit and the normalization of laboratory test, which documented the complete recovery of liver function. The intent of our work is to highlight the feasibility of single-agent carboplatin in ED-SCLC patients with tumor-related hepatic failure but preserved Eastern Cooperative Oncology Group PS, suggesting that this therapeutic option should not be discouraged a priori. Indeed, the identification of specific tools guiding physicians in the selection of patients who might benefit from the treatment is remarkably needed; meanwhile, the use of available prognostic score (e.g. Manchester score) might be of great value and should be considered in clinical practice. Anti-Cancer Drugs 32: 755-757 Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved