Cancer Treat. Rev. [JOURNAL]
Sun
200 papers
Opportunities and challenges for non-small cell lung cancer brain metastases in the immunotherapy era.
Yu Y, Luo Y, Zeng F … +1 more , Liu A
Cancer Treat Rev · 2025 Nov · PMID 40876405 · Publisher ↗
Brain radiotherapy (BRT) has traditionally been the mainstay of treatment for non-small cell lung cancer brain metastases (NSCLC-BM), given the low intracranial efficacy of conventional systemic therapies. In recent year...
Brain radiotherapy (BRT) has traditionally been the mainstay of treatment for non-small cell lung cancer brain metastases (NSCLC-BM), given the low intracranial efficacy of conventional systemic therapies. In recent years, immune checkpoint inhibitors (ICIs) have emerged as a standard treatment for advanced NSCLC without actionable driver mutations and have shown promising benefits in patients with BM. However, their intracranial efficacy remains modest, as the highest reported intracranial objective response rate and median intracranial progression-free survival in first-line populations reaching only 56.3 % and 12.7 months, respectively, which is likely explained by restricted blood-brain barrier permeability, the immunosuppressive tumor microenvironment within BM, and both primary and acquired resistance to ICIs. Preclinical evidence suggests that BRT can synergize with ICIs by enhancing antitumor immunity and overcoming immune resistance, primarily through blood-brain barrier disruption and tumor microenvironment remodeling. Consistently, encouraging clinical outcomes have been reported with the combination of BRT and ICI (BRT-ICI) in NSCLC-BM, while prospective data remain scarce. A recent phase II trial reported some of the most favorable outcomes to date with BRT-ICI plus chemotherapy, showing an intracranial objective response rate of 82.5 %, a median intracranial progression-free survival of 16.1 months, and a median overall survival of 20.9 months in treatment-naive patients with NSCLC-BM. Despite these advances, the optimal schedule of BRT-ICI remains controversial, with ongoing debates on treatment sequencing, timing, and radiation dose-fractionation. Additionally, critical challenges persist, including the risk of neurological toxicity, particularly radiation necrosis, and the absence of predictive biomarkers for patient selection. This review summarizes the current advances in ICI-based systemic therapies for NSCLC-BM, discusses the existing opportunities and progress of BRT-ICI, and reflects on challenges in optimizing this strategy in the immunotherapy era.
Advances in the management of locally advanced rectal cancer: A shift toward a patient-centred approach to balance outcomes and quality of life.
Airoldi M, Roselló S, Tarazona N … +7 more , Huerta M, Pérez-Santiago L, Fleitas T, Pla-Martí V, Puccini A, Roda D, Cervantes A
Cancer Treat Rev · 2025 Nov · PMID 40858040 · Publisher ↗
The treatment of locally advanced rectal cancer (LARC) has undergone a significant evolution in recent years, shifting toward more selective strategies that balance oncological outcomes with quality of life (QoL) preserv...
The treatment of locally advanced rectal cancer (LARC) has undergone a significant evolution in recent years, shifting toward more selective strategies that balance oncological outcomes with quality of life (QoL) preservation. Total neoadjuvant treatment (TNT) has improved local control and reduced distant metastases, but its long-term toxicities have sparked growing interest in treatment de-escalation strategies aimed at minimizing adverse effects while maintaining efficacy. This review focuses on the therapeutic advancements for LARC, analysing both established standards and emerging innovations. We discuss the increasing adoption of organ-preserving approaches, particularly the Watch-and-Wait (WW) strategy for patients achieving a clinical complete response (cCR), and potentially the selective omission of radiotherapy in well-defined cases. Additionally, we explore and examine less invasive surgical techniques that preserve function without compromising cure rates. Beyond standard treatment approaches, we highlight the role of immunotherapy, particularly its breakthrough efficacy in LARC with deficient mismatch repair/microsatellite instability (dMMR/MSI), leading to the concept of immune-ablation: achieving complete tumor regression while sparing patients from chemotherapy, radiotherapy, and surgery. Ongoing research is investigating immunotherapy's potential role also in proficient mismatch repair/microsatellite stable (pMMR/MSS) LARC. Finally, we discuss emerging predictive biomarkers, such as circulating tumor DNA (ctDNA) and radiomics, which might refine patient selection and guide treatment individualization. The future of LARC management lies in a precision-driven approach, where survival is optimized without compromising QoL. By embracing innovation and personalizing care, we are entering a new era where cure remains paramount, but never at the expense of the patient's well-being.
The emerging role of PARP inhibitors in prostate cancer: A narrative review.
Lobianco L, Calvanese G, D'Ausilio D … +15 more , Rossetti S, Cecere SC, Ventriglia J, Pisano C, Tambaro R, Napoli MD, Passarelli A, Roma C, Luca A, Sepe F, Cozzolino S, Perri E, Lamia MR, Moccia C, Pignata S
Cancer Treat Rev · 2025 Nov · PMID 40848312 · Publisher ↗
Prostate cancer (PC) is the second most common cancer and the fifth leading cause of cancer mortality in men, worldwide. Genomic analysis identified alterations in DNA damage repair (DDR) pathways, in up to 30% of metast...
Prostate cancer (PC) is the second most common cancer and the fifth leading cause of cancer mortality in men, worldwide. Genomic analysis identified alterations in DNA damage repair (DDR) pathways, in up to 30% of metastatic castration-resistant prostate cancer (mCRPC). Homologous recombination repair (HRR) mutations in BRCA1/2 emerged as a relevant biomarker in PC, linked to aggressive behavior, unfavorable outcomes and notable responses to poly-ADP ribose polymerase inhibitors (PARPi). While PARPi efficacy in BRCA-mutated mCRPC is well established, their role in earlier disease stages is currently under investigation. This non-systematic narrative review aims to summarize current evidence on PARPi in PC, outlining approved indications, ongoing clinical trials, and emerging therapeutic strategies across different disease settings.
Invasive lobular carcinoma: Strategies and perspectives from the lobular breast cancer research group.
Corso G, Shen S, Criscitiello C … +22 more , Mukhtar R, Gamble L, Rocco EG, Pesapane F, Nicosia L, Jhaveri K, Salimbeni BT, Massari G, Meduri E, De Scalzi AM, Concardi A, Magnoni F, Mamtani A, Pareja F, Leonardi MC, Sacchini V, Bogani G, Vecchia C, Presti D, Colleoni MA, Veronesi P, Robson ME
Cancer Treat Rev · 2025 Nov · PMID 40815983 · Publisher ↗
Invasive lobular carcinoma (ILC) represents approximately 10-15% of all breast cancers and is defined by a unique discohesive morphology due to loss of E-cadherin. Despite its prevalence, ILC has been historically underr...
Invasive lobular carcinoma (ILC) represents approximately 10-15% of all breast cancers and is defined by a unique discohesive morphology due to loss of E-cadherin. Despite its prevalence, ILC has been historically underrepresented in clinical and translational research, contributing to diagnostic, therapeutic, and prognostic uncertainties. This narrative review, conducted by the Invasive Lobular Carcinoma Research Group, synthesizes current evidence on ILC with expert perspectives to inform future research and clinical strategies. We highlight the distinct biology of ILC, including characteristic genomic alterations (e.g., CDH1, PIK3CA, ERBB2 mutations) and its relationship with endocrine sensitivity and limited immune infiltration. Diagnostic challenges are underscored by ILC's subtle imaging presentation and underestimation of tumor extent on mammography and ultrasound, with MRI and contrast-enhanced mammography offering improved accuracy. The review discusses evolving surgical approaches, axillary staging considerations, and radiotherapy strategies, with an emphasis on adapting techniques to ILC's infiltrative growth. Endocrine therapy remains central for hormone receptor-positive ILC, with emerging evidence supporting CDK4/6 inhibitors and extended endocrine therapy in high-risk cases. Investigational therapies targeting ILC-enriched mutations and synthetic lethality mechanisms (e.g., ROS1 inhibition in CDH1-deficient tumors) hold promise for personalized treatment. This comprehensive review identifies knowledge gaps and advocates for histology-specific clinical trials, biomarker-driven treatment strategies, and tailored imaging and surgical techniques to improve outcomes for patients with ILC.
Combining antibody-drug conjugates with immune checkpoint inhibitors: A new paradigm for breast cancer therapy.
Xu X, Yu T, Wang Z
Cancer Treat Rev · 2025 Nov · PMID 40815982 · Publisher ↗
The use of antibody-drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs) has revolutionized the treatment of breast cancer. ADCs deliver cytotoxic payloads to tumor cells via antigen-targeted monoclonal antibod...
The use of antibody-drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs) has revolutionized the treatment of breast cancer. ADCs deliver cytotoxic payloads to tumor cells via antigen-targeted monoclonal antibodies, triggering direct cytotoxicity and immunomodulatory effects such as immunogenic cell death (ICD), antibody-dependent cellular cytotoxicity (ADCC), and dendritic cell activation. Preclinical and clinical studies highlight the synergistic effect of combining ADCs with ICIs: ADCs enhance tumor immunogenicity by releasing neoantigens, while ICIs reinvigorate T-cell-mediated antitumor responses by blocking the PD-1/PD-L1 or CTLA-4 pathways. This review explores the synergistic potential of combining ADCs and ICIs in the treatment of breast cancer, with an emphasis on mechanistic synergy and clinical outcomes. Notably, overlapping toxicities require careful monitoring. Additionally, novel immune checkpoint-targeted drug conjugates (IDCs) exhibit potential through dual-targeting and immunomodulatory mechanisms. Future efforts should focus on optimizing patient selection and developing next-generation conjugates to maximize efficacy while minimizing adverse effects.
Immune checkpoint inhibitor-related neurotoxicity: Incidence and management. A systematic review and meta-analysis.
Nielsen DL, Juhl CB, Chen IM … +3 more , Wang Y, Nielsen OH, Santomasso BD
Cancer Treat Rev · 2025 Nov · PMID 40795646 · Publisher ↗
BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved outcomes for various malignancies. However, serious immune-related adverse events (irAEs), including neurologic complications (NAEs), may occur. The aim of th...
BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved outcomes for various malignancies. However, serious immune-related adverse events (irAEs), including neurologic complications (NAEs), may occur. The aim of this study was to examine the incidence and spectrum of NAEs and evaluate management strategies for reducing their impact. METHODS: Two studies were conducted: 1) A meta-analysis of phase I-IV clinical trials involving adults with malignancies treated with ICIs, either as monotherapy, in combination with other ICIs, or with chemotherapy. The primary outcome was the incidence of (ir)NAEs, summarized using a meta-analysis with a random-effects model. 2) A systematic review of the literature addressing the clinical manifestations and treatment of irNAEs. RESULTS: The meta-analysis included 657 unique trials with 91,340 participants. For all ICIs, the incidence of all-grade NAEs was 0.24% (95% CI, 0.15-0.32%). Cerebral events, cerebrovascular accidents, were increased post-treatment and accounted for 54% of all grade-5 events in clinical trials. Among 991 reported irNAE cases, 77% of patients improved with treatment; however, 42% experienced unresolved sequelae and the overall mortality rate was 17.1%. Among patients with overlapping myasthenia gravis, myositis, and myocarditis ("Triple M"), the mortality reached 38%; primarily due respiratory failure (50%) or cardiotoxicity (41%). CONCLUSIONS: Although the incidence of ICI-related NAEs is low such side effects may lead to severe morbidity and mortality. In patients with Triple M syndrome intensive respiratory function monitoring and support are essential parameters to improve the outcome. PROSPERO Protocol # CRD42023463750.
How to foster new treatment development in ultra-rare tumours? Joint EMA-EORTC multi-stakeholder workshops on ultra-rare sarcomas as a model for rare cancers.
Stacchiotti S, Pantziarka P, Leonard H … +43 more , Voltz C, Abatedaga L, Bouche G, Bouygues C, Bovee JVMG, Van der Graaf WTA, Rojas T, D'Ambrosio L, Donoghue M, Enzmann H, Feeney G, Foggi P, Frezza AM, Herold R, Jones RL, Kasper B, Roes K, Marreaud S, Miceli R, Robinson D, Sommer J, Tap WD, Tydings C, Trama A, Houdt WV, van Oortmerssen G, Wagner AJ, Widemann B, Gelderblom H, Gronchi A, Napolitano A, Dufresne A, Fumagalli ER, Baldi G, Marquina G, Koseła-Paterczyk H, Martin Javier JB, Junker N, Rutkowski P, Oyen WJG, Lacombe D, Pignatti F, Demolis P
Cancer Treat Rev · 2025 Nov · PMID 40789252 · Publisher ↗
Ultra-rare sarcomas (URS) and ultra-rare cancers (URC) represent a unique challenge in oncology due to their rarity, heterogeneity, and the severe unmet clinical needs of affected patients. In 2024, the European Medicine...
Ultra-rare sarcomas (URS) and ultra-rare cancers (URC) represent a unique challenge in oncology due to their rarity, heterogeneity, and the severe unmet clinical needs of affected patients. In 2024, the European Medicines Agency (EMA) and the European Organisation for Research and Treatment of Cancer (EORTC) convened two multi-stakeholder workshops, bringing together regulators, clinicians, researchers, and patient advocates. These workshops aimed to explore innovative strategies for treatment development and establish a framework for future collaboration. Key issues were discussed, including the scarcity of biological and clinical data, major barriers in conducting randomized trials, and limited pharmaceutical investment. A key outcome was the unanimous commitment of all stakeholders, including regulatory agencies such as EMA and the U.S. FDA, to work together towards pragmatic solutions. Participants recognized the necessity of flexible regulatory approaches, alternative trial designs, and meaningful endpoints tailored to ultra-rare conditions. The workshops also highlighted the importance of global collaboration, early regulatory engagement, and leveraging existing mechanisms like orphan drug designation and conditional approvals. The discussions emphasized that while scientific rigor must be upheld, regulatory frameworks must adapt to the specific challenges posed by URS. Stakeholders pledged to maintain open dialogue, share expertise, and develop innovative infrastructures to accelerate progress. This collaborative commitment marks a critical step forward in addressing the high unmet needs of URS. By fostering a unified effort among diverse stakeholders, the workshops established a model for advancing treatments in other URC, prioritizing patient outcomes while navigating the complexities of drug development for these challenging diseases.
Checkpoint inhibitor benefit in perioperative gastro-esophageal cancer: A meta-analysis of phase III trials.
Zhao JJ, Yi Ng KY, Sundar R … +1 more , Klempner SJ
Cancer Treat Rev · 2025 Nov · PMID 40779895 · Publisher ↗
BACKGROUND: The integration of immunotherapy (IO) with perioperative chemotherapy represents an advance in locally advanced, resectable gastroesophageal cancers. However, randomized controlled trials (RCTs) have yielded...
BACKGROUND: The integration of immunotherapy (IO) with perioperative chemotherapy represents an advance in locally advanced, resectable gastroesophageal cancers. However, randomized controlled trials (RCTs) have yielded discordant findings with respect to event-free survival (EFS) and overall survival (OS), particularly when differing chemotherapy backbones and IO agents are employed. Understanding the sources and implications of these discrepancies is essential for optimizing treatment strategies. Here, we sought to compare outcomes between perioperative FLOT-based and cisplatin/fluoropyrimidine based regimens when combined with IO, and to evaluate the consistency of FLOT-only arms across major RCTs in locally advanced gastroesophageal cancers. METHODS: RCTs investigating the role of perioperative combination chemotherapy with IO in patients with locally advanced gastro-esophageal cancer were included. Kaplan-Meier curves were digitally reconstructed to obtain individual patient data. Survival analyses incorporated testing for the proportional hazards assumption and were supplemented with piecewise and pooled random-effects analyses to address time-dependent effects and between-study heterogeneity. RESULTS: No significant difference in EFS was observed between the FLOT-durvalumab and FLOT-pembrolizumab arms (HR = 0.907, 95 %-CI: 0.637-1.290, p = 0.586). FLOT-IO regimens showed superior EFS compared to Cis/fluoropyrimidine-IO (HR = 0.790, 95 %-CI: 0.647-0.966, p = 0.021) as well as FLOT-only (HR = 0.732, 95 %-CI: 0.610-0.878, p < 0.001). While EFS curves for FLOT-only arms converged on long-term follow-up, OS curves diverged, with increased heterogeneity across FLOT-only arms apparent beyond 24 months. Notwithstanding, these analyses should be interpreted with caution due to the lack of patient-level covariate adjustment across trials. CONCLUSION: As we await the mature OS data from MATTERHORN, the addition of IO to perioperative FLOT should be considered the preferred standard-of-care in resectable, locally-advanced gastro-esophageal adenocarcinoma. Our comparative analyses suggest that FLOT remains a favored chemotherapy backbone for perioperative IO, but confirmation from future randomized trials with mature survival data is needed.
Circulating tumor DNA as prognostic marker in patients with metastatic colorectal cancer undergoing systemic therapy: A systematic review and meta-analysis.
Holz A, Paul B, Zapf A … +2 more , Pantel K, Joosse SA
Cancer Treat Rev · 2025 Sep · PMID 40743933 · Publisher ↗
BACKGROUND: The response to systemic therapy against metastatic colorectal cancer (mCRC) is currently assessed by radiologic imaging. However, an increasing number of studies have shown that circulating tumor DNA (ctDNA)...
BACKGROUND: The response to systemic therapy against metastatic colorectal cancer (mCRC) is currently assessed by radiologic imaging. However, an increasing number of studies have shown that circulating tumor DNA (ctDNA) as liquid biopsy can be used as an alternative method to assess therapy efficacy. We conducted a systematic review with subsequent meta-analysis of primary studies to assess the prognostic value of sequential liquid biopsies in patients with metastatic colorectal cancer treated with systemic therapy. METHODS: Randomized, non-randomized, and prospective observational studies, reporting on the change in ctDNA concentration in total cell-free DNA over the course of systemic therapy of patients treated for metastatic colorectal cancer to predict treatment response according to RECIST criteria were included. RESULTS: Fifty-six studies involving 3735 evaluable patients with metastatic colorectal cancer were included in the meta-analysis. ctDNA increase during systemic therapy as compared to baseline was strongly associated with progression-free survival (HR: 2.44, 95% CI: 2.02-2.95) and overall survival (HR: 2.53, 95% CI: 2.01-3.18), which were reported in 39 and 33 studies, respectively. CONCLUSION: Our analyses underscore the strong prognostic value of longitudinal plasma-based ctDNA analysis through liquid biopsy in mCRC patients. Subsequent research should evaluate the role of ctDNA in guiding therapy decisions, particularly in identifying patients likely to benefit from continuation or change of systemic therapy. While further standardization of ctDNA testing remains necessary, current evidence supports integrating serial ctDNA monitoring into upcoming clinical mCRC intervention trials, to lay the groundwork for its inclusion into future RECIST versions. PROTOCOL REGISTRATION: The protocol for this review was registered on PROSPERO (CRD42023420012).
Tepotinib in patients with MET exon 14 skipping non-small cell lung cancer.
Paik PK, Iams WT, Husain H … +3 more , O'Hara RM, Adewusi E, Le X
Cancer Treat Rev · 2025 Sep · PMID 40738075 · Publisher ↗
The management of non-small cell lung cancer (NSCLC) has been transformed by the identification of specific therapies which target oncogenic drivers, including MET exon 14 (METex14) skipping, which occurs in 3-4% of pati...
The management of non-small cell lung cancer (NSCLC) has been transformed by the identification of specific therapies which target oncogenic drivers, including MET exon 14 (METex14) skipping, which occurs in 3-4% of patients. The development of selective MET inhibitors, such as tepotinib, has provided much-needed oral, targeted treatment options for these patients who otherwise have poor outcomes. In the largest trial involving patients with METex14 skipping NSCLC, the Phase II VISION study, tepotinib demonstrated robust and durable efficacy, which was especially notable when used in the first-line setting. Subgroup analyses demonstrated consistent efficacy in older and younger patients, Asian patients, and patients with brain metastases. The trial supported initial approval of tepotinib in Japan in 2020 and later in the US (accelerated approval: 2021; full approval: 2024) and many other countries worldwide. Here we delve into published literature on tepotinib, overview the mechanism of action and pharmacology, and provide a deep-dive into data from the pivotal VISION study, examining long-term outcomes, insights relevant for treatment sequencing, and biomarker analyses. We also discuss real-world data for tepotinib, indirect comparisons versus immuno- and/or chemotherapy, and provide experience from clinical practice, including guidance on managing adverse events, to provide a valuable aid for clinical practitioners.
Management changes and survival outcomes for cancer patients after multidisciplinary team discussion; a systematic review and meta-analysis.
Williams GJ, Thompson JF
Cancer Treat Rev · 2025 Sep · PMID 40714369 · Publisher ↗
OBJECTIVE: Multidisciplinary team (MDT) review of cancer patients has become routine in many institutions worldwide. The process seeks to ensure correct diagnosis and staging, optimise treatment decisions and improve out...
OBJECTIVE: Multidisciplinary team (MDT) review of cancer patients has become routine in many institutions worldwide. The process seeks to ensure correct diagnosis and staging, optimise treatment decisions and improve outcomes. The aim of this study was to measure any differences in management and survival of cancer patients reviewed at an MDT meeting compared to patients not reviewed or with management plans made prior to MDT review. METHODS AND ANALYSIS: A PRISMA-compliant systematic review was undertaken with searches of Medline, Embase and the Cochrane Trials Register to 7 June 2024, with no restrictions on language or era. RESULTS: From 2832 titles, 179 comparative studies were identified. Hazard ratios (HRs) for death, generated from multivariable analyses, were reported in 37 studies that included 56,187 patients but estimates were highly variable (I 87 %), ranging from HR 0.1 to 0.96. While the magnitude of the benefit for patients after MDT review was variable, all 37 studies reported a reduced risk of death for MDT-reviewed patients compared to non-reviewed patients. Sub-group analyses based on the patient's cancer type reduced heterogeneity in patients with breast and hepatocellular carcinomas and suggested a reduced risk of death in MDT-reviewed patients compared to those not reviewed (HR 0.86, 95 %CI 0.79-0.93, I 56 %, p = 0.0001 and HR 0.82, 95 %CI 0.76-0.88, I 36 %, p < 0.00001, respectively). CONCLUSION: Extensive evidence shows a survival benefit for cancer patients discussed at an MDT meeting but there is considerable variation in the reported magnitude of that benefit, ranging from a 4% to a 90% reduction in the risk of death.
The importance of education and training in neuroendocrine neoplasms: challenges and opportunities for multidisciplinary management.
Panzuto F, Barbi S, Trama A … +1 more , Fazio N
Cancer Treat Rev · 2025 Sep · PMID 40714368 · Publisher ↗
Neuroendocrine neoplasms (NENs) exemplify the challenges and opportunities inherent in managing rare cancers. Their rarity, biological heterogeneity, and diagnostic complexity necessitate a highly structured and multidis...
Neuroendocrine neoplasms (NENs) exemplify the challenges and opportunities inherent in managing rare cancers. Their rarity, biological heterogeneity, and diagnostic complexity necessitate a highly structured and multidisciplinary approach to patient care. In this context, education and training emerge as central pillars for improving clinical outcomes. This review highlights how integrating multidisciplinary teams of diverse medical specialties enhances diagnostic accuracy, refines therapeutic strategies, and ensures adherence to evolving best practices. Establishing dedicated training pathways-both through traditional educational models and innovative digital platforms-is crucial to address the unique learning needs posed by NENs. Scientific societies play a pivotal role by producing guidelines and fostering continuous professional development, although notable variability across international recommendations emphasizes the need for clinicians to harmonize and interpret critically. Patient advocacy groups, meanwhile, have become essential actors in the educational ecosystem, bridging informational gaps and advocating for patient-centered research and policy initiatives. Emerging technologies, particularly artificial intelligence, offer promising tools to support clinical education and decision-making, provided that their implementation is cautious, validated, and integrated under healthcare professionals' guidance. By analyzing the NEN model, this review underscores that the future of rare cancer management relies on building strong collaborative networks, promoting standardized yet flexible educational programs, and embracing technological innovation, always focusing on quality, safety, and patient-centered care.
Exercise in patients with metastatic prostate cancer: A comprehensive review.
Muñoz-Carrillo FJ, Garcia de Herreros M, Carrillo D … +8 more , Peralta O, Aversa C, Fernández-Mañas L, Ferrer-Mileo L, Altamirano M, Reig Torras Ò, Jimenez N, Mellado B
Cancer Treat Rev · 2025 Sep · PMID 40712215 · Publisher ↗
Prostate cancer (PC) is one of the most prevalent malignancies worldwide. Metastatic PC remains an incurable disease, with the androgen receptor (AR) pathway being the primary driver of tumor progression and the main tar...
Prostate cancer (PC) is one of the most prevalent malignancies worldwide. Metastatic PC remains an incurable disease, with the androgen receptor (AR) pathway being the primary driver of tumor progression and the main target for therapeutic strategies. Thus, patients usually undergo long-term treatments, particularly androgen deprivation therapy (ADT), which can worsen the intrinsic deterioration in quality of life (QoL) caused by the disease burden. Increasing evidence supports the use of physical activity (PA) and structured exercise (EX) as complementary measures to mitigate treatment-related adverse effects and improve clinical outcomes across tumor types. EX has shown benefits across multiple systems and plays a significant role in modulating tumor progression through several cellular pathways. Furthermore, it has confirmed potential to alleviate cancer-related symptoms while enhancing functional capacity and tolerability of treatment. This review gathers the current evidence regarding the impact of PA and EX on patients with metastatic PC, integrating both epidemiological and interventional studies. Despite promising findings, most of the available evidence is documented on non-metastatic populations, highlighting the need for directed studies in advanced disease settings. Future research is needed in metastatic PC patients, in order to assess long-term impacts of EX in this population.
De-escalation strategies with targeted therapies in non-small cell lung cancer.
Bortolot M, Remon J, Bironzo P … +10 more , Cortiula F, Menis J, Chan SW, van Geel R, Reguart N, Arrieta O, Mountzios G, Dingemans AC, Besse B, Hendriks LEL
Cancer Treat Rev · 2025 Sep · PMID 40684707 · Publisher ↗
Targeted therapies (TT) for non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGA), particularly EGFR-mutant and ALK-rearranged tumors, have become the standard of care across nearly all stages of t...
Targeted therapies (TT) for non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGA), particularly EGFR-mutant and ALK-rearranged tumors, have become the standard of care across nearly all stages of the disease. However, the arbitrarily defined dose and treatment duration of TT, as well as the financial cost of these drugs, reduce their availability worldwide. Pharmacokinetic and pharmacodynamic properties of TT suggest that doses of some TT are overestimated as there is limited evidence supporting a direct relationship between therapeutic intensity and outcomes. This can lead to overtreatment of patients, resulting in an increased risk of toxicity without enhanced efficacy. Some academic initiatives have been launched aiming to explore de-escalating strategies with TT, either reducing the dose or the duration of these drugs. These approaches can decrease the risk of adverse events positively impacting patients' quality of life, without compromising efficacy, while reducing economic impact. In this review, we summarize current data regarding de-escalating strategies with TT, ongoing trials and challenges of this approach.
FGFR2b protein overexpression: An emerging biomarker in gastric and gastroesophageal junction adenocarcinoma.
Smyth EC, Kim KM, Rha SY … +4 more , Wainberg ZA, Honeycutt H, Sommermann E, Ochiai A
Cancer Treat Rev · 2025 Sep · PMID 40680491 · Publisher ↗
Gastric and gastroesophageal junction cancer (G/GEJC) is a heterogeneous and complex disease characterized by histologic and molecular subtypes. Although a growing number of treatments have improved survival outcomes in...
Gastric and gastroesophageal junction cancer (G/GEJC) is a heterogeneous and complex disease characterized by histologic and molecular subtypes. Although a growing number of treatments have improved survival outcomes in the advanced setting, the greatest therapeutic benefits are observed among patient populations eligible for biomarker-directed therapies. Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) is an emerging biomarker under phase 3 clinical investigation for G/GEJC with the novel monoclonal antibody bemarituzumab. FGFR2b protein overexpression in gastric cancer, together with its function in various oncogenic signaling pathways, makes it an attractive target for precision medicine and thereby has gained clinical interest for its potential prognostic role in G/GEJC. Thus, to explore the potential role of FGFR2b, this narrative review summarizes the role and mechanism of FGFR2b in advanced G/GEJC, describes appropriate detection methodology for FGFR2b protein overexpression, and discusses future considerations for precision treatment in advanced G/GEJC with respect to FGFR2b protein overexpression and the emergence of other biomarkers.
Palliative systemic therapy for locally advanced or metastatic salivary duct carcinoma: A comprehensive review.
Kanno M, Kano S, Imamura Y … +9 more , Kawakita D, Narita N, Tada Y, Ito Y, Morikawa T, Imoto Y, Kato Y, Takabayashi T, Fujieda S
Cancer Treat Rev · 2025 Sep · PMID 40680490 · Publisher ↗
Salivary duct carcinoma (SDC) is a rare and highly aggressive malignancy of the salivary glands. For patients ineligible for curative surgery or definitive radiotherapy, treatment options remain limited owing to the abse...
Salivary duct carcinoma (SDC) is a rare and highly aggressive malignancy of the salivary glands. For patients ineligible for curative surgery or definitive radiotherapy, treatment options remain limited owing to the absence of standardized therapeutic protocols. This review draws upon major salivary gland cancer guidelines and integrates molecular profiles with clinical response data to propose an evidence-based treatment algorithm that stratifies patients into four groups according to the expression status of human epidermal growth factor receptor 2 (HER2) and androgen receptor (AR). In HER2-positive tumors, HER2-targeted therapy constitutes the standard of care, with trastuzumab plus docetaxel providing clinical benefit. Antibody-drug conjugates, such as trastuzumab deruxtecan, have demonstrated efficacy even in patients with disease progression during trastuzumab-based therapy. In AR-positive tumors, androgen deprivation therapy, particularly combined androgen blockade, has demonstrated clinical activity, though concurrent molecular characteristics may influence treatment outcomes. In HER2-positive/AR-positive tumors, HER2-targeted therapy is generally prioritized, although the absence of validated predictive biomarkers and defined thresholds remains a clinical challenge. For HER2-negative and AR-negative tumors, or those refractory to either or both targeted approaches, cytotoxic chemotherapy remains a viable option. Immune checkpoint inhibitors may offer benefits in tumors with high PD-L1 expression, although data on their role in SDC remain limited. Next-generation sequencing is recommended to identify actionable alterations (e.g., NTRK, BRAF, FGFR, HRAS) that may guide targeted therapy or clinical trial enrollment. Integrating comprehensive molecular profiling into treatment decision-making is essential to optimizing outcomes in advanced SDC.
Corrigendum to "Trastuzumab deruxtecan in human epidermal growth factor receptor 2-positive breast cancer brain metastases: A systematic review and updated meta-analysis" [Cancer Treat. Rev. 133 (2025) 102882].
Michelon I, Castro CER, Madeira T … +6 more , Dacoregio MI, Stecca C, Soares LR, Saeed A, Vilbert M, Cavalcante L
Cancer Treat Rev · 2025 Sep · PMID 40670239 · Publisher ↗
Abstract loading — click title to view on PubMed.
Long-term surveillance recommendations for young adult cancer survivors.
Egger-Heidrich K, Wolters F, Frick M … +6 more , Halbsguth T, Müller T, Woopen H, Tausche K, Richter D, Gebauer J
Cancer Treat Rev · 2025 Sep · PMID 40651064 · Publisher ↗
BACKGROUND: Advancements in cancer treatment have led to increased survival rates among young adult cancer survivors (YACS). However, these individuals face unique long-term health risks, including secondary malignancies...
BACKGROUND: Advancements in cancer treatment have led to increased survival rates among young adult cancer survivors (YACS). However, these individuals face unique long-term health risks, including secondary malignancies, cardiovascular disease, and psychosocial challenges. Effective long-term surveillance strategies are critical to mitigating these risks and improving health outcomes. This scoping review aims to summarize existing recommendations for long-term surveillance of YACS, identify gaps in current guidelines, and highlight areas for future research. METHODS: A scoping review was conducted using Pubmed focusing on peer-reviewed literature published between January 2015 and January 2025 that addresses post-treatment (>5 years after diagnosis) follow-up strategies for YACS. The review synthesizes recommendations across various cancer types, treatment modalities, and long-term effects. RESULTS: The review identified 32 recommendations. Of all eligible articles initially retrieved, 169 different articles were included after screening and eligibility. Findings indicate a lack of standardized, age-specific surveillance guidelines, with most recommendations adapted from pediatric or adult oncology frameworks. Emerging evidence suggests that risk-based, personalized surveillance approaches-incorporating genetic predisposition, treatment history, and lifestyle factors-may optimize long-term health outcomes. DISCUSSION: This review underscores the need for age-appropriate, evidence-based surveillance guidelines tailored to YACS and highlights the importance of multidisciplinary care models to support survivorship. Future research should focus on developing standardized, risk-stratified surveillance protocols and evaluating their impact on health outcomes.
T-cell engager toxicity in clinical phase trials; A systematic review and meta-analysis.
Zaïr ZM, Butterworth G, Shalaby M … +2 more , Oštarijaš E, Thisthlethwaite F
Cancer Treat Rev · 2025 Sep · PMID 40644745 · Publisher ↗
Engineered to activate a patient's own immune response, T Cell Engagers (TCEs) are positioned to mediate T cell directed cytotoxicity through targeted engagement of a tumour antigen. Despite their attractive properties T...
Engineered to activate a patient's own immune response, T Cell Engagers (TCEs) are positioned to mediate T cell directed cytotoxicity through targeted engagement of a tumour antigen. Despite their attractive properties TCE therapies have yet to be widely used in the treatment of solid tumours with several obstacles that include adverse toxicity profiles. This systematic review and meta-analysis assessed the toxicity associated with T-cell engagers (TCEs) in the treatment of solid tumours. Papers were sourced from MEDLINE, Cochrane Library, CINHL, EMBASE, Web of Knowledge, Scopus. Prevalence data from the identified primary studies was pooled using an inverse variance method with a restricted maximum likelihood estimator. Freeman-Tukey double arcsine transformation to determine toxicity prevalence and confidence intervals. A total of 1147 publications were identified of which 30 were included for systematic review. Toxicity profiles from 17 TCEs, comprising 9 different ligands that utilised the CD3, CD40, CD28 or CD64 signalling pathways were characterised in this study. Of these studies, 21 publications were included for meta-analysis, focussing on four TCEs: catumaxomab, ertumaxomab, tebentafusb, and MDX-H210. Meta-analysis found that the most prevalent toxicities were gastrointestinal and inflammatory. Subgroup analysis revealed that Gastrointestinal toxicity (GI) toxicity was independent of tumour type or ligand. Cytokine Release Syndrome (CRS) is potentially being under-reported due to challenges of differentiation of CRS from other inflammatory mediated constituent symptoms, although Fc-independent TCEs were linked to lower inflammatory toxicity. The review highlights TCE-dependent toxicity profiles and highlights key features that may ameliorate TCE tolerance.
Systematic literature review of intravenous versus subcutaneous administration of oncology therapies: A clinical, economic and patient perspective.
George S, Bourlon MT, Overman MJ … +6 more , Dixon M, Shelley K, Markus KJ, Kewley RM, Pope SI, Albigès L
Cancer Treat Rev · 2025 Sep · PMID 40592035 · Publisher ↗
Subcutaneous (SC) formulations of oncology therapies offer a potentially less time-consuming and more convenient alternative to intravenous (IV) administration. However, exploring the potential benefits of SC over IV adm...
Subcutaneous (SC) formulations of oncology therapies offer a potentially less time-consuming and more convenient alternative to intravenous (IV) administration. However, exploring the potential benefits of SC over IV administration from a broader perspective is necessary to understand the larger-scale impact. In this systematic literature review (SLR), we evaluated the efficacy, pharmacokinetics/pharmacodynamics (PK/PD), safety, and patient and healthcare provider (HCP) preference for SC/IV oncology therapies, along with differences in patient outcomes, costs, and time requirements. The SLR was conducted in January 2019 and updated in May 2023, and included 169 publications. Studies providing comparative results between IV and SC formulations regarding clinical, economic, and patient outcomes were included. The focus was anticancer therapies for which both IV and SC formulations are being developed in phase 3 clinical trials, or are regulatory approved. SC administration was associated with savings in HCP time and patient chair time. Direct and indirect cost-savings were also observed. Increased treatment satisfaction and patient/HCP preference was reported with SC administration, as was improved caregiver productivity. The relative tolerability of SC and IV formulations for oncology drugs was similar; however, a higher incidence of injection-site reactions was reported with SC administration. Overall survival, PK/PD, and overall response rate results were comparable between IV and SC administration. This SLR demonstrates that SC and IV administration had comparable efficacy, PK/PD, and tolerability profiles, with SC administration associated with cost and time savings, and generally preferred by patients and HCPs. Therefore, SC administration of oncology therapies may offer advantages over IV administration.
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