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Introduction: Platinum-based chemotherapy represents the standard of care (SoC) for the first-line treatment of advanced urothelial carcinoma (mUC). The benefit of adding immune checkpoint inhibitors (ICIs) to platinum-based chemotherapy was recently investigated. We performed an individual patient data (IPD) meta-analysis of phase 3 clinical trials comparing ICI-based treatments., Methods: A systematic literature search was conducted on the MEDLINE and CENTRAL databases. The results were filtered by including only reports on clinical trials or randomized clinical trials from 2018 to 2023, including 3047 patients from four clinical trials (EV302, CHECKMATE-901, IMVIGOR130, KEYNOTE-361). An IPD meta-analysis was performed by reconstructing IPD from Kaplan-Meier curves. The primary endpoints were overall survival (OS) and progression-free survival (PFS) of Pembrolizumab + EV compared to experimental arms of the other trials of immunotherapy + chemotherapy., Results: The OS analysis showed an advantage of IPD from EV302 vs. all the other trials. For EV302 vs. KEYNOTE-361, the HR was 0.51; for EV302 vs. IMVIGOR130, the HR was 0.47; and for EV302 vs. CHECKMATE-901, the HR was 0.66 (CI 95% 0.51-0.85). In the PFS analysis, the EV302 arm showed a statistically significant advantage compared to CHECKMATE-901 (HR 0.66) and versus IMVIGOR130 (HR 0.51)., Limitations: By using reconstructed IPD curves, it was not possible to adjust patient-level covariates, and the heterogeneity of the included population may have affected the pooled results., Conclusions: The EV302 experimental arm showed better OS and PFS when compared to the other immunochemotherapy combinations. An immunochemotherapy combination strategy at the beginning of treatment in mUC seems to be superior in terms of OS and PFS compared to platinum-based chemotherapy alone. EV-Pembrolizumab resulted to have better outcomes compared to avelumab, rather than other immunochemotherapy combinations. However, given the heterogeneity of these studies, a longer follow up and prospective trials are needed to confirm these data.

In the last two-decades, innovative drugs have revolutionized cancer treatments, demonstrating a significant improvement in overall survival. These drugs may present several pharmacokinetics interactions with non-oncological drugs, and vice versa, and, non-oncological drugs can modify oncological treatment outcome both with pharmacokinetic interaction and with an "off-target impact" on the tumor microenvironment or on the peripheral immune response. It's supposed that the presence of a drug-drug interaction (DDI) is associated with an increased risk of reduced anti-tumor effects or severe toxicities. However, clinical evidence that correlate the DDI presence with outcome are few, and results are difficult to compare because of difference in data collection and heterogeneous population. This review reports all the clinical evidence about DDI to provide an easy-to-use guide for DDI management and dose adjustment in solid tumors treated with inhibitors of the cyclin-dependent kinases CDK4-6, Antibody-drug conjugates, Poly ADPribose polymerase inhibitors, androgen-receptor targeted agents, or immunecheckpoints inhibitors., Competing Interests: Declaration of Competing Interest All the authors declare no conflicts of interest for this manuscript., (Copyright © 2024. Published by Elsevier B.V.)

The use of neoadjuvant or perioperative anti-PD(L)1 was recently tested in multiple clinical trials. We performed a systematic review and meta-analysis of randomised trials comparing neoadjuvant or perioperative chemoimmunotherapy to neoadjuvant chemotherapy in resectable NSCLC. Nine reports from 6 studies were included. Receipt of surgery was more frequent in the experimental arm (odds ratio, OR 1.39) as was pCR (OR 7.60). EFS was improved in the experimental arm (hazard ratio, HR 0.55) regardless of stage, histology, PD-L1 expression (PD-L1 negative, HR 0.74) and smoking exposure (never smokers, HR 0.67), as was OS (HR 0.67). Grade > = 3 treatment-related adverse events were more frequent in the experimental arm (OR 1.22). The experimental treatment improved surgical outcomes, pCR rates, EFS and OS in stage II-IIIB, EGFR/ALK negative resectable NSCLC; confirmatory evidence is warranted for stage IIIB tumours and with higher maturity of the OS endpoint., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DM: none. FTG: none. SP: none. MADC: none. AT: none. RG: none. AJG: none. MR: none. MV: none. EM: none. RT: none. FLC: none. LL: none. PN: none. NP: none. MO: sub-investigator in KEYNOTE-671. MB: none. PMF: consultant for Amgen, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo Company, F-Star, G1 Therapeutics, Genentech, Iteos, Janssen Global Services LLC, Merck, Novartis, SANOFI PASTEUR INC, Surface Oncology; grant/contract (to institution) from AstraZeneca, BioNTech, Bristol-Myers Squibb, Corvus, Kyowa Hakko Kirin, LUNGevity Foundation, Mark Foundation, NCI Cancer Center Support Grant, Novartis, Regeneron Pharmaceuticals, Stand Up To Cancer; gift (research funding) from Bloomberg Philantropies, Earl & Darielle Linehan, Martha Furman, Susan Troll. SVL: advisory board/consultant for Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Catalyst, Daiichi Sankyo, Eisai, Elevation Oncology, Genentech/Roche, Gilead, Guardant Health, Janssen, Jazz Pharmaceuticals, Merck, Merus, Mirati, Novartis, Regeneron, Sanofi, Takeda, Turning Point Therapeutics; research grant (to institution) from Alkermes, Elevation Oncology, Genentech, Gilead, Merck, Merus, Nuvalent, RAPT, Turning Point Therapeutics; data safety monitoring board for Candel Therapeutics. AB: none. SN: consultant for Thermo Fisher Scientific; grant/contract (to institution) from Amgen, AstraZeneca, BeiGene Switzerland GmbH, Boehringer Ingelheim, Eli Lilly and Company, F. Hoffmann-La Roche, Merck Sharp and Dohme, Novartis, PFIZER CANADA INC, SANOFI PASTEUR INC, Takeda Oncology; speaker bureau from AstraZeneca, BeiGene Switzerland GmbH, Bristol-Myers Squibb, Novartis, Takeda Oncology. GC: none. EC: none. FF: none. FC: personal fees from Roche/Genentech, AstraZeneca, Takeda, Pfizer, Bristol-Myers Squibb, Merck Sharp & Dohme, Lilly, and Bayer. DS: Advisory Board role and speaker honoraria with Astra Zeneca, MSD, BMS, Astellas, Janssenn, EISAI, Merck, Pfizer, Bayer, Novartis, Astra Zeneca, Lilly., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Oligometastatic disease has been described as an intermediate clinical state between localized cancer and systemically metastasized disease. Recent clinical studies have shown prolonged survival when aggressive locoregional approaches are added to systemic therapies in patients with oligometastases. The aim of this review is to outline the newest options to treat oligometastatic colorectal cancer (CRC), also considering its molecular patterns. We present an overview of the available local treatment strategies, including surgical procedures, stereotactic body radiation therapy (SBRT), thermal ablation, as well as trans-arterial chemoembolization (TACE) and selective internal radiotherapy (SIRT). Moreover, since imaging methods provide crucial information for the early diagnosis and management of oligometastatic CRC, we discuss the role of modern radiologic techniques in selecting patients that are amenable to potentially curative locoregional treatments., Competing Interests: Declaration of Competing Interest The authors disclose no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Chemokines are small, secreted peptides involved in the mediation of the immune cell recruitment. Chemokines have been implicated in several diseases including autoimmune diseases, viral infections and also played a critical role in the genesis and development of several malignant tumors. CXCL12 is a homeostatic CXC chemokine involved in the process of proliferation, and tumor spread. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors, that is still lacking effective therapies and with a dramatically poor prognosis., Method: We conducted a scientific literature search on Pubmed and Google Scholar including retrospective, prospective studies and reviews focused on the current research elucidating the emerging role of CXCL12 and its receptors CXCR4 - CXCR7 in the pathogenesis of pancreatic cancer., Results: Considering the mechanism of immunomodulation of the CXCL12-CXCR4-CXCR7 axis, as well as the potential interaction with the microenvironment in the PDAC, several combined therapeutic approaches have been studied and developed, to overcome the "cold" immunological setting of PDAC, like combining CXCL12 axis inhibitors with anti PD-1/PDL1 drugs., Conclusion: Understanding the role of this chemokine's axis in disease initiation and progression may provide the basis for developing new potential biomarkers as well as therapeutic targets for related pancreatic cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Roberto, Arrivi, Di Civita, Barchiesi, Pilozzi, Marchetti, Santini, Mazzuca and Tomao.)