Programmed death ligand 1 (PD-L1) expression, assessed by the combined positive score (CPS), is an established predictive biomarker for first-line chemo-immunotherapy in metastatic triple-negative breast cancer (mTNBC). In routine practice, CPS testing is heterogeneous and its relationship with outcomes in later-line, sacituzumab govitecan (SG)-treated patients with mTNBC is not well described. We aimed to assess clinicopathological correlates of CPS and its association with survival in this cohort. We conducted a retrospective, multicenter study within the Central European Breast Cancer Collaboration (CEBCC)-102 project. CPS was locally assessed by validated immunohistochemistry. Survival outcomes: overall survival (OS), post-metastatic survival (PMS), and metastasis-free interval, were assessed with the Kaplan-Meier method. Of 303 women from the Czech Republic, Poland, and Slovakia with mTNBC treated with SG in ≥ 2 line, 107 (35.3%) with available CPS results were included in this analysis. CPS was positive (≥ 10) in 51/107 patients (47.7%) without significant demographic or disease-specific differences. During a median follow-up of 40 months, CPS-positive status may suggest worse outcomes in this cohort in multivariate analysis despite partial first-line chemo-immunotherapy exposure: OS 41.6 versus 67.7 months (HR 2.2, 95% CI: 1.1-4.5, p = 0.027) and PMS 20.2 versus 27.1 months (HR = 2.3, 95% CI: 1.2-4.2, p = 0.009). In this selected cohort, CPS status did not correlate with clinicopathological characteristics, but CPS-positive status was associated with inferior survival outcomes. Given the selection and survivor bias inherent to later-line treatment cohorts and the incomplete availability of CPS, these findings should be considered hypothesis-generating.
In heavily pretreated patients with metastatic triple-negative breast cancer (mTNBC), further systemic therapy offers limited benefit and increased toxicity. Recognizing the end-of-life (EOL) phase in time helps avoid overtreatment and ensure goal-concordant care. This study analyzed the interval between the last oncologist visit and death in pretreated women with mTNBC, as well as systemic therapy status, palliative care involvement and related factors. This multinational ambispective cohort study included women with mTNBC who received ≥2 lines of palliative systemic therapy and died between June 20, 2022 and June 20, 2025. Data from 17 centers in Poland, the Czech Republic and Slovakia were extracted from medical records. The primary endpoint was the interval between the final oncologist visit and death. 183 women with median age at death 53.6 years (28.6-86.5) were included. Patients had a median of 4 prior palliative chemotherapy lines (2-12) and the median interval from last oncologist visit to death was 17 days (0-410). At the final visit, 29.5 % continued systemic therapy and 49 % had prior palliative care involvement. Longer intervals were associated with PS 0-1 vs ≥ 2 (p = 0.005), while palliative care involvement had no significant effect (p = 0.849). The results highlight the need for earlier recognition of clinical decline and timely palliative care in mTNBC. Limiting non-beneficial systemic therapy near EOL supports symptom control, autonomy, and quality of life. Despite European efforts, including the Network of Expertise on Complex and Poor Prognosis Cancers, structured EOL planning remains a major gap.
Tumor hypoxia is a major driver of tumor progression and metastasis. Hypoxic adaptation is regulated by hypoxiainducible factor-1 (HIF-1), which controls the transcription of genes promoting malignant behavior. HIF-1 inhibitors have failed as monotherapies in clinical trials, highlighting the need for combination-based strategies. This study aimed to develop hypoxia-targeted combination therapies for breast and ovarian cancers. Using established in vitro and in vivo hypoxia models, we evaluated acriflavine, a HIF-1 inhibitor, in combination with paclitaxel and an epithelial-mesenchymal transition targeting agent. Acriflavine exerted potent antiproliferative effects, particularly in triple-negative breast cancer cell lines, and proteomic profiling indicated modulation of migration, proliferation, and cellular metabolism. The acriflavine-paclitaxel combination showed synergistic antitumor and antimetastatic activity, which was further enhanced by rolipram. Overall, our findings support hypoxia-targeted combination approaches and provide a biological rationale for combining HIF-1 inhibition with immune checkpoint blockade in breast cancer.
In recent years, particular attention has been paid to the possible connections, similarities, and potential uses of animals, especially pets (dogs and cats), in research on the causes, characteristics, and treatment of cancers occurring in pets and humans. One of the most promising experimental research models used to explore these issues is the avian embryo chorioallantoic membrane (CAM). This review aims to highlight the problem of the occurrence of cancers in domestic animals, placing emphasis on types, incidence, and predispositions of dogs and cats. Methodology and applications in cancer studies of this unique model were presented in detail. Moreover, the advantages and disadvantages of this diagnostic tool, as well as potential and future perspectives, were also described. This review confirms that cancer research can be conducted without the use of animals. Furthermore, the CAM can provide a robust and reliable model for this type of research and provide translational potential as an ethical, cost-effective model bridging laboratory and clinical research.
Our study assessed the prevalence of CHEK2 gene variants, including low-penetrance variants (lp-CHEK2: p.I157T, p.S428F, p.T476M) and their association with clinicopathological parameters in cancer patients and controls. Germline genetic analysis of 1,280 breast and ovarian cancer (BOC), 191 young breast (<33 years, yBr), 568 nonbreast (non-BOC) and 96 endocrine cancer patients was performed using the Illumina TruSight Hereditary Cancer Panel. CHEK2 disease-causing (pathogenic/likely pathogenic) variants were more frequent in the BOC and yBr groups (2 and 2.6%) compared to non-BOC and endocrine tumour patients (0.5% and 0%, p=0.049). Lp-CHEK2 variants were detected in 4% of all groups and associated with other disease-causing genetic abnormalities more often than pathogenic/likely pathogenic CHEK2 variants (16% vs. 1%, p<0.0001). Despite their frequent occurrence, lp-CHEK2 variants confer a negligible risk of breast cancer and show no association with other tumour types. Disease-causing CHEK2 variants, however, have implications for the clinical management of breast cancer patients according to current guidelines.
Oncology clinical trials play a pivotal role in the development of new therapeutic options; however, their implementation remains an extremely costly and time-consuming process. Artificial intelligence can open new horizons in the design and conduct of clinical trials, particularly in early phases, where safety, dose planning, and patient recruitment efficiency are critical. This paper aims to explore the potential applications of artificial intelligence in various stages of early-phase oncology trials, including biostatistical design, patient enrollment, and quality assurance aspects. Based on case studies and examples from the literature, it can be concluded that artificial intelligence can assist with precise protocol design, shorten recruitment timelines, and improve predictive performance in dose planning and patient selection, thereby reducing the number of adverse events. At the same time, regulatory, ethical, and data protection challenges remain significant barriers to the widespread adoption of artificial intelligence. Integrating artificial intelligence into clinical trials requires not only technological but also strategic-level modernization, from the industrial companies and authorities as well. The reliable and validated application of artificial intelligence could represent a major advancement in clinical research, particularly in increasing the success rate of early-phase trials. Orv Hetil. 2025; 166(47): 1857-1868. Az onkológiai klinikai vizsgálatok kiemelt szerepet töltenek be az új terápiás lehetőségek fejlesztésében, ezek megvalósítása azonban rendkívül költség- és időigényes folyamat. A mesterséges intelligencia új távlatokat nyithat a klinikai vizsgálatok tervezésében és végrehajtásában, különösen a korai fázisokban, amelyeknél a biztonságosság, a dózistervezés és a betegbevonás hatékonysága kulcsfontosságú. A közlemény célja a mesterséges intelligencia alkalmazási lehetőségeinek feltárása a korai fázisú onkológiai vizsgálatok különböző szakaszaiban, beleértve a biostatisztikai tervezést, a betegek toborzását, valamint a minőségbiztosítás szempontjait is. Esettanulmányok és irodalmi példák alapján megállapítható, hogy a mesterséges intelligencia képes segíteni a protokollok pontosabb tervezését, lerövidítheti a toborzási időt, valamint javíthatja a prediktív hatékonyságot a dózistervezés és a betegkiválasztás terén, ezáltal csökkentve a nemkívánatos események számát. Ugyanakkor a szabályozási, etikai és adatvédelmi kihívások továbbra is jelentős akadályt képeznek a mesterséges intelligencia széles körű elterjedése előtt. A mesterséges intelligencia integrálása a klinikai vizsgálatokba nem csupán technológiai, hanem stratégiai szintű modernizációt is igényel mind az ipari szereplők, mind a hatóságok részéről. A mesterséges intelligencia megbízható, validált alkalmazása jelentős előrelépést jelenthet a klinikai vizsgálatok terén, különösen a korai klinikai fázisok sikerességének növelésében. Orv Hetil. 2025; 166(47): 1857–1868.
Prolgolimab is an IgG1 anti-PD-1 monoclonal antibody with the Fc-silencing 'LALA' mutation. The phase III DOMAJOR study assessed efficacy and safety of prolgolimab in combination with pemetrexed and platinum-based chemotherapy vs placebo in combination with pemetrexed and platinum-based chemotherapy as first-line treatment for advanced non-small cell lung cancer (NSCLC). 292 patients with advanced non-squamous NSCLC were randomized 1:1 to receive 4 cycles of pemetrexed, platinum-based drug and either prolgolimab (3 mg/kg Q3W) or placebo followed by prolgolimab/placebo with pemetrexed until disease progression or toxicity (≤36 months). The primary endpoint was overall survival (OS). After a median follow-up of 18 months, the median OS was not reached (95 % CI, 22.28 - NA) in the prolgolimab-combination group vs 14.6 months (95 % CI, 11.73 - 19.15) in the placebo-combination group (HR, 0.51; 95 % CI, 0.35 - 0.73, p = 0.0001). The OS improvement was independent of PD-L1 status. Median progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) was 7.7 months in the prolgolimab-combination group and 5.5 months in the placebo-combination group (HR, 0.65; 95 % CI, 0.49 - 0.85, p = 0.0004). The only adverse events that were reported in at least 10 % of the patients that were significantly more frequent in the prolgolimab-combination group were blood creatinine increased and dyspnoea. Among patients with advanced NSCLC the addition of prolgolimab to pemetrexed and a platinum-based drug increased OS and PFS, with no new safety concerns. This benefit was retained in patients with PD-L1 negative tumors. (ClinicalTrials.gov, NCT03912389).
Pediatric extracranial solid tumors continue to pose significant challenges due to their rarity and heterogeneity. However, the diagnosis and treatment of these diseases have undergone substantial transformation in recent years, largely driven by the growing use of molecular pathology techniques. The increasingly detailed mapping of genetic and epigenetic alterations, along with gene expression patterns, enables more accurate tumor classification, prognostic stratification, and the identification of targeted therapeutic options. This paper illustrates the clinical relevance of molecular approaches in routine pediatric oncology practice through examples including pediatric soft tissue sarcomas, neuroblastoma, and vascular anomalies. It also highlights the potential of this evolving paradigm. The manuscript provides an in-depth discussion of the applicability of emerging technologies – such as next-generation sequencing, and optical genome mapping – in advancing our understanding of tumor biology, improving diagnostic accuracy, and guiding optimal treatment strategies. Furthermore, it addresses the germline genetic background of these pediatric tumors, the detection of therapeutically actionable genetic alterations, and the clonal evolution associated with treatment resistance.Orv Hetil. 2025; 166(40): 1563–1573. A gyermekkori extracranialis szolid tumorok ritkaságukból és változatosságukból adódóan a mai napig komoly kihívást jelentenek, ugyanakkor e betegségek diagnosztikája és kezelése az elmúlt években jelentős átalakuláson ment keresztül a molekuláris patológiai módszerek térnyerésének köszönhetően. A genetikai és epigenetikai eltérések, valamint a génexpressziós mintázatok egyre részletesebb feltérképezése lehetővé teszi a daganatok pontosabb osztályozását, prognosztikai besorolását és célzott terápiás lehetőségek azonosítását. A jelen közlemény a gyermekkori lágyrész-sarcomák, a neuroblastoma, valamint a vascularis anomáliák példáján keresztül mutatja be a molekuláris szemlélet klinikai jelentőségét a mindennapokban, valamint előrevetíti az ebben a megközelítésben rejlő lehetőségeket. Részletesen tárgyalja az új technológiák – köztük az újgenerációs szekvenálás és az optikai genomtérképezés – alkalmazási lehetőségeit e betegségek biológiájának mélyebb feltárásában, pontosabb diagnosztikájában és az optimális kezelési stratégia felállításában. Kitér e gyermekkori tumorok kialakulásának csíravonali genetikai hátterére, a terápiásan célozható genetikai eltérések kimutatásának lehetőségeire és a terápiarezisztencia hátterében álló klonális változásokra egyaránt. Orv Hetil. 2025; 166(40): 1563–1573.
Rectal cancer (RC) remains a significant global health concern, with increasing incidence rates and associated mortality. Early detection of metastases plays a crucial role in the effective management of rectal cancer and predicting patient outcomes. Imaging modalities are vital in diagnosing and evaluating the extent of metastases. The integration of novel hybrid positron emission tomography utilizing fluorodeoxyglucose (18F-FDG) fused with magnetic resonance (PET/MR) has emerged as an innovative diagnostic tool. By combining both technologies' strengths, PET/MR imaging provides precise metabolic information from PET alongside detailed anatomical data from MR. This prospective study aimed to assess the clinical utility of PET/MR imaging with the 18F-FDG tracer compared to standard imaging modalities for detecting the extent of RC. We enrolled 42 patients who underwent both standard imaging (CT and/or MRI) and whole-body PET/MR with 18F-FDG before preoperative therapy. Our results indicated that PET/MR with 18F-FDG provides superior detection of lymph nodes and tumor deposits in the mesorectum, with the highest diagnostic accuracy for tumor length measurement (area under the ROC curve (AUC) = 0.730; p < 0.05) and a combined model of SUVmax and CEA (AUC = 0.921; p < 0.001). Furthermore, PET/MR changed the clinical stage in 64% of patients and altered clinical management in 26% of cases.  CONCLUSIONS: The presented findings demonstrate the effectiveness of this advanced imaging technique and its potential to enhance treatment planning. By providing more accurate staging information, this method could significantly improve diagnosis, treatment customization, and overall outcomes for patients with rectal cancer, particularly in cases where lymph node involvement and tumor deposits impact therapeutic decisions.
Introduction: Research suggests more and more advantages of the early introduction of palliative care in parallel with active oncology treatment. Numerous studies have proven an increase in overall survival, a better quality of life for the patient and their relatives, and a reduction in the psychological exhaustion of the medical staff. It is proven that patients are hospitalized less often and spend less time on active beds. The treatment of patients with advanced cancer is incomplete without integrated, personalized, support services. At the same time, there is still no internationally accepted criteria system based on which it can be easily determined exactly when and which patients need special palliative care. Objective: Our goal was to create a criteria system that can be easily used in everyday patient care and supports patient management, which helps in determining whether it is recommended to refer the patient to the special palliative care system. Method: After reviewing the literature, we created a checklist consisting of 1 + 8 questions, and then examined it through content analysis of three focus groups in which family physicians, oncologists, and palliative care physicians participated. Results: The representatives of the three professions most involved in the care of patients with advanced cancer all found the decision support point system useful and recommended its use in everyday patient care. Family doctors would use it as an indicator, and oncologists would use it as preparatory material for the oncological team decision. The questions of the data sheet were modified according to the suggestions of the experts, and the final version is presented in this article. Conclusion: The research confirmed that a uniform score system can help assess patients’ needs and organize cooperation between professions, facilitate patient journeys, and its automatic application can greatly improve patients’ access to appropriate care. At the same time, before its introduction, it is definitely necessary to increase the number of specialist palliative care providers, so that the expected significantly increased number of patients does not overload the existing system. Orv Hetil. 2025; 166(41): 1603–1610. Bevezetés: A palliatív szakellátás korai, az aktív onkológiai kezeléssel párhuzamos bevezetésének egyre több előnyét igazolják a kutatások. Számos tanulmány bizonyította a túlélés növekedését, a beteg és a hozzátartozók jobb életminőségét, az egészségügyi személyzet pszichés kimerültségének csökkenését. A betegek ritkábban kerülnek kórházba, és kevesebb időt töltenek aktív ágyakon. Az előrehaladott állapotú daganatos betegek kezelése nem teljes az integrált, személyre szabott, támogató szolgáltatások nélkül, ugyanakkor még továbbra sincs olyan, nemzetközileg is elfogadott kritériumrendszer, amely alapján könnyen meghatározható lenne, hogy pontosan mikor és melyik betegnek van szüksége speciális palliatív ellátásra. Célkitűzés: Célunk a mindennapi betegellátásban is könnyen használható, a betegirányítást támogató szempontrendszer létrehozása volt, amely segít annak meghatározásában, hogy javasolt-e a beteget a speciális palliatív ellátórendszerbe referálni. Módszer: A szakirodalom áttekintése után létrehoztunk egy 1 + 8 kérdésből álló döntéstámogató pontozási rendszert, majd három fókuszcsoport tartalomelemzésével vizsgáltuk meg háziorvosok, onkológusok és palliatív orvosok részvételével. Eredmények: Az előrehaladott állapotú daganatos betegek ellátásában leginkább érintett három szakma képviselői mind hasznosnak találták a döntéstámogató pontrendszert, és a mindennapi betegellátásban való felhasználását javasolták. A családorvosok indikátorként, az onkológusok pedig az onkoteam döntéselőkészítő anyagaként alkalmaznák. Az adatlap kérdéseit a szakértők javaslatai szerint módosítottuk, és a végleges változatot a jelen cikkben mutatjuk be. Következtetés: A kutatás megerősítette, hogy egy egységes pontrendszer segíthet a betegek igényeinek felmérésében, és rendezheti a szakmák közötti együttműködést, könnyíti a betegutakat, automatikus alkalmazása sokban javíthatja a betegek megfelelő ellátáshoz való hozzájutását. A bevezetése előtt ugyanakkor mindenképp szükség van a palliatív szakellátók számának növelésére, hogy a várhatóan jelentősen megnövekvő betegszám ne terhelje túl a meglévő rendszert. Orv Hetil. 2025; 166(41): 1603–1610.
Over the years since the 4th Breast Cancer Consensus Conference, a substantial body of new evidence based on clinical trial results has been published, necessitating an update of the 2020 recommendations. This professional guideline primarily reflects the current ESMO, NCCN, ABC, and St. Gallen Consensus Conference statements and recommendations. From a didactic perspective, the text first addresses early-stage breast cancer, followed by locally advanced, locoregionally recurrent, and metastatic breast cancer. At the beginning of both the early-stage and metastatic breast cancer sections, we provide a summary of general principles relevant to the respective field, which apply to the subsequent subsections. Within these subsections, therapeutic options are discussed according to genomic subgroups. At the end of the recommendations, considerations for the management of certain rare clinical scenarios are summarized. The appendices cover, among other topics, multidisciplinary team (tumor board) requirements, recommended chemotherapy protocols, and the definition of menopause.
Cervical cancer (CC) is a global health issue, despite the availability of effective preventive measures. The objective of this investigation was to evaluate the comprehension of CC and its preventive measures among 17-25-year-old female students living in southern Poland, to compare the results with the data obtained in 2012 and to propose actionable recommendations for improving the current state of affairs. The study collected data from 464 female students during a ten-month period in 2022 using a pre-validated tool developed by our group, CCKP-64 categorized into sections: personal information, basic CC knowledge, risk factor assessment, awareness of primary and secondary prevention, and sources of information. The 98.92% of participants were aware of CC, 42.24% linked it to an infection. Genetic factors and human papillomavirus (HPV) infection were commonly identified as risk factors. Most of the participants (81.90%) knew about the Pap smear and planned to undergo the test (74.74%). The most common sources of information were the Internet (81.68%), family and friends (46.77%), and medical staff (42.89%). Comparison with the 2012 cohort indicated a decrease in awareness of HPV vaccine existence (69.85% vs. 53.23%, p<0.001) and cytological examination (91.21% vs. 81.90%, p<0.001), but increase in percentage of vaccinated population (9.35% vs. 19.43%, p=0.001). The insufficient knowledge and deteriorating trends in CC prevention among young women over the last decade are concerning. The proportion of vaccinated women remains unsatisfactory. Measures to enhance awareness of national reimbursed HPV vaccination program are necessary.
Vaccination has been considered the most crucial defence against viral infections, including SARS-CoV-2. Numerous reports have demonstrated the effectiveness of the above vaccines in oncological patients. It has also been proven that, apart from vaccinations and oncological therapy, the course of the cancer process itself influences the magnitude of the humoral response, especially in people after infection with SARS-CoV-2. The phenomenon we observe seems to confirm the presence of a "natural" defence potential in a cancer patient's body, in this case, directed against infection with a viral pathogen. A "stronger" antiviral response also explains the asymptomatic course of SARS-CoV-2 infection in some of the above patients. To what extent the SARS-CoV-2 infection weakened the "natural" potential of the anticancer response in these patients remains an open question. This study aimed to answer the question about the impact of the cancer process on the humoral response in oncological patients vaccinated against SARS-CoV-2 infection and in patients after COVID-19. One thousand six hundred and sixty-eight people were observed. Over 2 years, 5,082 SARS-CoV-2 IgG and IgM antibody samples were determined. The concentration of antibodies was assessed in groups of oncological patients: those undergoing anticancer therapy after contracting COVID-19 and those after vaccination against the SARS-CoV-2 infection. The obtained results indicate a naturally more significant humoral response in oncological patients who have not been vaccinated and have not undergone anticancer therapy, such as radiotherapy, chemotherapy, or surgical intervention. The above observation applies to patients with breast, lung, colon, kidney, and testicular cancer, although the response varies significantly depending on the type of cancer.
Immune checkpoint inhibition (ICI) is effective for replication-repair-deficient, high-grade gliomas (RRD-HGG). The clinical/biological impact of immune-directed approaches after failing ICI monotherapy is unknown. We performed an international study on 75 patients treated with anti-PD-1; 20 are progression free (median follow-up, 3.7 years). After second progression/recurrence (n = 55), continuing ICI-based salvage prolonged survival to 11.6 months (n = 38; P < 0.001), particularly for those with extreme mutation burden (P = 0.03). Delayed, sustained responses were observed, associated with changes in mutational spectra and the immune microenvironment. Response to reirradiation was explained by an absence of deleterious postradiation indel signatures (ID8). CTLA4 expression increased over time, and subsequent CTLA4 inhibition resulted in response/stable disease in 75%. RAS-MAPK-pathway inhibition led to the reinvigoration of peripheral immune and radiologic responses. Local (flare) and systemic immune adverse events were frequent (biallelic mismatch-repair deficiency > Lynch syndrome). We provide a mechanistic rationale for the sustained benefit in RRD-HGG from immune-directed/synergistic salvage therapies. Future approaches need to be tailored to patient and tumor biology. Hypermutant RRD-HGG are susceptible to checkpoint inhibitors beyond initial progression, leading to improved survival when reirradiation and synergistic immune/targeted agents are added. This is driven by their unique biological and immune properties, which evolve over time. Future research should focus on combinatorial regimens that increase patient survival while limiting immune toxicity. This article is featured in Selected Articles from This Issue, p. 201.
Hepatic visceral crisis (VC), characterized by a rapid total bilirubin increase with disease progression, poses a life-threatening risk in advanced breast cancer (ABC). International consensus guidelines define VC and touch on impending VC (IVC). Limited data exist on systemic treatments for hepatic VC/IVC. This study explores the safety and efficacy of cisplatin monotherapy in patients with Human Epidermal Growth Factor Receptor 2- negative breast cancer (BC) and hepatic IVC/VC. In this retrospective single-center cohort study data of patients treated with cisplatin monotherapy (60-80 mg/m2, every 3-4 weeks) between 2016 and 2023 at a reference Cancer Centre in Southern Poland were analyzed. 33 female patients (24/33 hormonal-positive) with the mean age 53.84 years were included. Participants progressed on median 2 prior palliative systemic treatment lines. In 10/23 patients hepatic VC and in 23/33 IVC (rapid, symptomatic liver progression; extensive liver involvement; alanine or aspartate aminotransferase > 2 × normal limit; significant increases in lactate dehydrogenase, alkaline phosphatase, or gamma-glutamyl transferase) were identified. Median progression-free survival was 1.87 months and median overall survival 2.67 months. 33% of the patients presented stable disease or partial response. Eight patients experienced adverse events grade ≥ 3: in five the dose of cisplatin was reduced; two stopped the treatment. Due to the hepatotoxicity of BC-active drugs, specific recommendations for systemic treatment are scarce. Our study explored cisplatin's potential use, finding it to be a viable option in patients with performance status 0 or 1 experiencing hepatic IVC/VC, irrespective of liver function parameters and other factors.
The OlympiA randomized phase III trial compared 1 year of olaparib (OL) or placebo (PL) as adjuvant therapy in patients with germline BRCA1/2, high-risk human epidermal growth factor receptor 2-negative early breast cancer after completing (neo)adjuvant chemotherapy ([N]ACT), surgery, and radiotherapy. The patient-reported outcome primary hypothesis was that OL-treated patients may experience greater fatigue during treatment. Data were collected before random assignment, and at 6, 12, 18, and 24 months. The primary end point was fatigue, measured with the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Secondary end points, assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 item, included nausea and vomiting (NV), diarrhea, and multiple functional domains. Scores were compared between treatment groups using mixed model for repeated measures. Two-sided P values <.05 were statistically significant for the primary end point. All secondary end points were descriptive. One thousand five hundred and thirty-eight patients (NACT: 746, ACT: 792) contributed to the analysis. Fatigue severity was statistically significantly greater for OL versus PL, but not clinically meaningfully different by prespecified criteria (≥3 points) at 6 months (diff OL v PL: NACT: -1.3 [95% CI, -2.4 to -0.2]; P = .022; ACT: -1.3 [95% CI, -2.3 to -0.2]; P = .017) and 12 months (NACT: -1.6 [95% CI, -2.8 to -0.3]; P = .017; ACT: -1.3 [95% CI, -2.4 to -0.2]; P = .025). There were no significant differences in fatigue severity between treatment groups at 18 and 24 months. NV severity was worse in patients treated with OL compared with PL at 6 months (NACT: 6.0 [95% CI, 4.1 to 8.0]; ACT: 5.3 [95% CI, 3.4 to 7.2]) and 12 months (NACT: 6.4 [95% CI, 4.4 to 8.3]; ACT: 4.5 [95% CI, 2.8 to 6.1]). During treatment, there were some clinically meaningful differences between groups for other symptoms but not for function subscales or global health status. Treatment-emergent symptoms from OL were limited, generally resolving after treatment ended. OL- and PL-treated patients had similar functional scores, slowly improving during the 24 months after (N)ACT and there was no clinically meaningful persistence of fatigue severity in OL-treated patients.
Real-world cabozantinib use has increased since its approval to treat patients with advanced renal cell carcinoma (RCC) in 2016. We reviewed cabozantinib use in real-world clinical practice and compared outcomes with pivotal cabozantinib randomized control trials (RCTs). This PRISMA-standard systematic literature review evaluated real-world effectiveness and tolerability of cabozantinib in patients with RCC (PROSPERO registration: CRD42021245854). Systematic MEDLINE, Embase, and Cochrane database searches were conducted on November 2, 2022. Eligible publications included ≥ 20 patients with RCC receiving cabozantinib. After double-screening for eligibility, standardized data were abstracted, qualitatively summarized, and assessed for risk of bias using the Newcastle-Ottawa Scale. Of 353 screened publications, 41 were included, representing approximately 11,000 real-world patients. Most publications reported cabozantinib monotherapy cohort studies (40/41) of retrospective (39/41) and multicenter (32/41) design; most included patients from North America and/or Europe (30/41). Baseline characteristics were demographically similar between real-world and pivotal RCT populations, but real-world populations showed greater variation in prevalence of prior nephrectomy, multiple-site/brain metastasis, and nonclear-cell RCC histology. Cabozantinib activity was reported across real-world treatment lines and tumor types. Overall survival, progression-free survival, and objective response rate values from pivotal RCTs were within the ranges reported for equivalent outcomes across real-world studies. Common real-world grade ≥ 3 adverse events were consistent with those in pivotal RCTs (fatigue, palmar-plantar erythrodysesthesia syndrome, diarrhea, hypertension), but less frequent. No new tolerability concerns were identified. Real-world RCC survival outcomes for cabozantinib monotherapy were broadly consistent with pivotal RCTs, despite greater heterogeneity in real-world populations.
Pembrolizumab plus lenvatinib has shown antitumor activity and acceptable safety in patients with platinum-refractory urothelial carcinoma (UC). To evaluate pembrolizumab plus either lenvatinib or placebo as first-line therapy for advanced UC in the phase 3 LEAP-011 study. Patients with advanced UC who were ineligible for cisplatin-based therapy or any platinum-based chemotherapy were enrolled. Patients were randomly assigned (1:1) to pembrolizumab 200 mg intravenously every 3 wk plus either lenvatinib 20 mg or placebo orally once daily. Dual primary endpoints were progression-free survival (PFS) and overall survival (OS). An external data monitoring committee (DMC) regularly reviewed safety and efficacy data every 3 mo. Between June 25, 2019 and July 21, 2021, 487 patients were allocated to receive lenvatinib plus pembrolizumab (n = 245) or placebo plus pembrolizumab (n = 242). The median time from randomization to the data cutoff date (July 26, 2021) was 12.8 mo (interquartile range, 6.9-19.3). The median PFS was 4.5 mo in the combination arm and 4.0 mo in the pembrolizumab arm (hazard ratio [HR] 0.90 [95% confidence interval {CI} 0.72-1.14]). The median OS was 11.8 mo for the combination arm and 12.9 mo for the pembrolizumab arm (HR 1.14 [95% CI 0.87-1.48]). Grade 3-5 adverse events attributed to trial treatment occurred in 123 of 241 patients (51%) treated with lenvatinib plus pembrolizumab and in 66 of 242 patients (27%) treated with placebo plus pembrolizumab. This trial was terminated earlier than initially planned based on recommendation from the DMC. The benefit-to-risk ratio for first-line lenvatinib plus pembrolizumab was not considered favorable versus pembrolizumab plus placebo as first-line therapy in patients with advanced UC. Lenvatinib plus pembrolizumab was not more effective than pembrolizumab plus placebo in patients with advanced urothelial carcinoma.
The level of participation in cancer screening is low in the Polish population. The aim of this study was to assess the opinions of centers providing cancer screening as to the reasons for the low frequency of cancer screening in Poland and possible methods to increase participation. In July 2020 433 centers in Poland carried out breast and/or cervical cancer screening. Of these, 136 centers decided to participate in the study. The study was conducted using an original questionnaire. The questions were addressed to opinion of centers about: reasons for the low frequency of cancer screening in Poland, methods to increase the frequency of cancer screening, pricing and motivating factors for providing cancer screening. Among opinions as to possible reasons for the low frequency of cancer screening in Poland related to the care-system, lack of encouragement from general practitioners, lack of invitations for cancer screening and lack of proper social advertising were most prevalent; whereas among reasons related to patients, a low awareness of cancer screening and fear of cancer diagnosis. The main methods that could potentially increase screening participation are considered to be the inclusion of cancer screening in mandatory periodic employee examinations, more activity by general practitioners, better promotion of screening by central institutions, and sending personal invitations. In conclude some interventions should be carried out to motivate people to break down barriers.
Trastuzumab has been the standard of care for the treatment of patients with ERBB2-positive breast cancer; however, cardiac events have been reported. This long-term follow-up study provides clinical evidence supporting the similarity of a trastuzumab biosimilar (SB3) to reference trastuzumab (TRZ). To compare cardiac safety and efficacy between SB3 and TRZ for patients with ERBB2-positive early or locally advanced breast cancer after up to 6 years of follow-up. This prespecified secondary analysis of a randomized clinical trial, conducted from April 2016 to January 2021, included patients with ERBB2-positive early or locally advanced breast cancer from a multicenter double-blind, parallel-group, equivalence phase 3 randomized clinical trial of SB3 vs TRZ with concomitant neoadjuvant chemotherapy who completed neoadjuvant and adjuvant treatment. In the original trial, patients were randomized to either SB3 or TRZ with concomitant neoadjuvant chemotherapy for 8 cycles (4 cycles of docetaxel followed by 4 cycles of fluorouracil, epirubicin, and cyclophosphamide). After surgery, patients continued SB3 or TRZ monotherapy for 10 cycles of adjuvant treatment per previous treatment allocation. Following neoadjuvant and adjuvant treatment, patients were monitored for up to 5 years. The primary outcomes were the incidence of symptomatic congestive heart failure and asymptomatic, significant decrease in left ventricular ejection fraction (LVEF). The secondary outcomes were event-free survival (EFS) and overall survival (OS). A total of 538 female patients were included (median age, 51 years [range, 22-65 years]). Baseline characteristics were comparable between the SB3 and TRZ groups. Cardiac safety was monitored for 367 patients (SB3, n = 186; TRZ, n = 181). Median follow-up was 68 months (range, 8.5-78.1 months). Asymptomatic, clinically significant LVEF decreases were rarely reported (SB3, 1 patient [0.4%]; TRZ, 2 [0.7%]). No patient experienced symptomatic cardiac failure or death due to a cardiovascular event. Survival was evaluated for the 367 patients in the cardiac safety cohort and an additional 171 patients enrolled after a protocol amendment (538 patients [SB3, n = 267; TRZ, n = 271]). No difference was observed in EFS or OS between treatment groups (EFS: hazard ratio [HR], 0.84; 95% CI, 0.58-1.20; P = .34; OS: HR, 0.61; 95% CI, 0.36-1.05; P = .07). Five-year EFS rates were 79.8% (95% CI, 74.8%-84.9%) in the SB3 group and 75.0% (95% CI, 69.7%-80.3%) in the TRZ group, and OS rates were 92.5% (95% CI, 89.2%-95.7%) in the SB3 group and 85.4% (95% CI, 81.0%-89.7%) in the TRZ group. In this secondary analysis of a randomized clinical trial, SB3 demonstrated cardiac safety and survival comparable to those of TRZ after up to 6 years of follow-up in patients with ERBB2-positive early or locally advanced breast cancer. ClinicalTrials.gov Identifier: NCT02771795.