No treatment has surpassed platinum-based chemotherapy in improving overall survival in patients with previously untreated locally advanced or metastatic urothelial carcinoma.
We conducted a phase 3, ...global, open-label, randomized trial to compare the efficacy and safety of enfortumab vedotin and pembrolizumab with the efficacy and safety of platinum-based chemotherapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma. Patients were randomly assigned in a 1:1 ratio to receive 3-week cycles of enfortumab vedotin (at a dose of 1.25 mg per kilogram of body weight intravenously on days 1 and 8) and pembrolizumab (at a dose of 200 mg intravenously on day 1) (enfortumab vedotin-pembrolizumab group) or gemcitabine and either cisplatin or carboplatin (determined on the basis of eligibility to receive cisplatin) (chemotherapy group). The primary end points were progression-free survival as assessed by blinded independent central review and overall survival.
A total of 886 patients underwent randomization: 442 to the enfortumab vedotin-pembrolizumab group and 444 to the chemotherapy group. As of August 8, 2023, the median duration of follow-up for survival was 17.2 months. Progression-free survival was longer in the enfortumab vedotin-pembrolizumab group than in the chemotherapy group (median, 12.5 months vs. 6.3 months; hazard ratio for disease progression or death, 0.45; 95% confidence interval CI, 0.38 to 0.54; P<0.001), as was overall survival (median, 31.5 months vs. 16.1 months; hazard ratio for death, 0.47; 95% CI, 0.38 to 0.58; P<0.001). The median number of cycles was 12 (range, 1 to 46) in the enfortumab vedotin-pembrolizumab group and 6 (range, 1 to 6) in the chemotherapy group. Treatment-related adverse events of grade 3 or higher occurred in 55.9% of the patients in the enfortumab vedotin-pembrolizumab group and in 69.5% of those in the chemotherapy group.
Treatment with enfortumab vedotin and pembrolizumab resulted in significantly better outcomes than chemotherapy in patients with untreated locally advanced or metastatic urothelial carcinoma, with a safety profile consistent with that in previous reports. (Funded by Astellas Pharma US and others; EV-302 ClinicalTrials.gov number, NCT04223856.).
Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In ...this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression.
EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged ≥18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540.
Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 85% were male and 105 15% were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 26·1 months (95% CI 22·1–31·8; 149 52% of 284 died) versus 13·3 months (10·5–16·2; 188 67% of 281 died) in the chemotherapy group (hazard ratio HR 0·57, 95% CI 0·46–0·71; p<0·0001), median progression-free survival was 8·1 months (95% CI 6·2–8·8; 214 events occurred) in the cemiplimab group versus 5·3 months (4·3–6·1; 236 events occurred) in the chemotherapy group (HR 0·51, 95% CI 0·42–0·62; p<0·0001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 6·6 months (6·1–9·3) and overall survival of 15·1 months (11·3–18·7). The most common grade 3–4 treatment-emergent adverse events were anaemia (15 4% of 356 patients in the cemiplimab group vs 60 17% of 343 in the control group), neutropenia (three 1% vs 35 10%), and pneumonia (18 5% vs 13 4%). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, n=1 each and general disorders or unknown n=2) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism n=2 each, and cardiac arrest, lung abscess, and myocardial infarction n=1 each). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signals
At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer.
Regeneron Pharmaceuticals and Sanofi.
We studied the comparative effectiveness of biosimilar filgrastim vs original filgrastim in patients with chemotherapy-induced neutropenia.
This multicenter, observational study was conducted at 14 ...centers. The study included 337 patients experiencing neutropenia under chemotherapy. Patients were given either filgrastim 30 MIU or 48 MIU (Neupogen
) or biosimilar filgrastim 30 MIU (Leucostim
). Data regarding age, chemotherapeutic agents used, number of chemotherapy courses, previous diagnosis of neutropenia, neutrophil count of patients after treatment, medications used for the treatment of neutropenia, and duration of neutropenia were collected. Time to absolute neutrophil count (ANC) recovery was the primary efficacy measure.
Ambulatory and hospitalized patients comprised 11.3% and 45.1% of the enrolled patients, respectively, and a previous diagnosis of neutropenia was reported in 49.3% of the patients, as well. Neutropenia occurred in 13.7% (n=41), 45.5% (n=136), 27.4% (n=82), 11.4% (n=34), and 2.0% (n=6) of the patients during the first, second, third, fourth, and fifth cycles of chemotherapy, respectively. While the mean neutrophil count was 0.53±0.48 before treatment, a significant increase to 2.44±0.66 was observed after treatment (
=0.0001). While 90.3% of patients had a neutrophil count <1.49 before treatment, all patients had a neutrophil count ≥1.50 after treatment. Neutropenia resolved within ≤4 days of filgrastim therapy in 60.1%, 56.7%, and 52.6% of the patients receiving biosimilar filgrastim 30 MIU, original filgrastim 30 MIU, and original filgrastim 48 MIU, respectively. However, there was no significant difference between the three arms (
=0.468). Similarly, time to ANC recovery was comparable between the treatment arms (
=0.332).
The results indicate that original filgrastim and biosimilar filgrastim have comparable efficacy in treating neutropenia. Biosimilar filgrastim provides a valuable alternative; however, there is need for further studies comparing the two products in different patient subpopulations.
Studies concerning adjuvant systemic therapy and prognosis in male breast carcinoma (MBC) are limited. We aimed to evaluate outcome of the changing practices of adjuvant systemic treatment and ...survival in operable MBC patients over the last two decades. The medical records of 148 MBC patients followed between the years 1986 and 2009 at 7 cancer center were evaluated retrospectively. One hundred and eighteen operable non-metastatic patients had sufficient data were included the study. One hundred and eighteen operable MBC were found to be eligible. Median age was 60 (range 29–83) years. Thirty-two percent of the patients had T3-4 tumors. Half of the patients had axillary lymph node-positive disease. The proportion of positivity of estrogen receptor(ER), progesterone receptor (PgR), and HER2 status were 82.9, 75.8, and 23.4%, respectively. Only, 7 patients had triple negative (TN). Adjuvant hormonotherapy was advised for 76.8% whereas adjuvant chemotherapy for 73.7% of the patients. Median follow-up was 40.9 months (range 3.8–186 months). Locoregional and/or distant recurrence developed in thirty-eight patients (32.2%). Twenty-three patients died during the follow-up period. Five-year disease-free survival (DFS) was found to be 60%, whereas overall survival (OS) was 82%. Larger tumor size and lymph node positivity were statistically significant poor prognostic factors for OS. Although statistical insignificant, patients with HER2-positive tumors have worse DFS (52 vs. 120 months, log rank
P
= .73) and OS (85 vs. 144 months, log rank
P
= .30) than HER2-negative ones. Although the frequency of the use of adjuvant systemic therapy in MBC has been increasing and survival rates improving for the last decades, lymph node status and tumor size are still the most important determining factors for prognosis. There is a need for further prognostic information in men with HER2-positive or TN breast cancer.
Locally advanced colorectal cancers are best treated with multivisceral resections. The aim of this study is to evaluate early and late results after multivisceral resections.
All patients operated ...for primary colorectal cancer between 2001 and 2010 were -reviewed. These were compared within the patients underwent single organ and multivisceral resections: demographics, tumor and procedure related parameters, perioperative results, early oncological outcomes and 5-year survival.
A total of 354 patients (59.6 ± 13.8 years old, 210 59.3% males) were abstracted. Ninety (25.4%) patients underwent multivisceral resections for clinical T4 tumors and en-bloc R0 resection was achieved in 82 (91.1%). Only 31 (34.4% and 8.8% of clinical T4 and all cancers, respectively) cases had actual adjacent organ invasions (pT4). Males (20%) had lower risk for locally advanced tumors than females (33.3%) (p < 0.05). PT4 cancers were more common, if the clinical T4 tumor is located in the colon (48.8% vs 21.3%; p < 0.01). Laparoscopy was seldom initiated and the risk of conversion was higher in clinical T4 tumors (p < 0.05). The rates of sphincter-saving procedures were not different. Operation time, bleeding and transfusion requirements increased when multivisceral resections were necessitated (p < 0.05), but hospital stay, complications and 30-day mortality rates were similar. The 5-year survival rates were identical (p > 0.05).
Clinical T4 tumors are not rare and more common in women. An actual invasion (pT4) may be observed in one third of all clinical T4 tumors, and more frequent in colon cancers. An en-bloc, R0, multivisceral resection may be achieved in most cases. Multivisceral resections do not alter the rates of sphincter-saving procedures, morbidity and 30-day mortality; do not worsen survival but increase operation time, intraoperative bleeding and perioperative transfusion requirements.
Prediction of the pathologic response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer is essential for optimal treatment strategy. The current approach of adjuvant ...or neoadjuvant treatment is based on the molecular subtype. Obesity may have affected chemotherapy response. This study aims to evaluate the relationship between metabolic activity of adipose tissue (AT) and pathological responses to NAC. And to define the association with body mass index (BMI) and metabolic parameters of standardized uptake value (SUV) of adipose tissue measured by positron emission computed tomography (PET/CT).
One-hundred and sixteen consecutive patients with stage II and III breast cancer who underwent PET/CT before receiving NAC, were evaluated in the study. Metabolic parameters of visceral adipose tissue (VAT-SUV), subcutaneous adipose tissue (SAT-SUV), and calculated SUV of visceral-to-subcutaneous ratio (V/S-ratio) were regarded. The relationship between SUV of AT and pathologic response was evaluated from medical records retrospectively.
Univariate-analysis revealed that good pathological response was significantly associated with clinical stage (P<.001), HER-2 positivity (P<.001), VAT-SUV (P=.037), VAT-density (P=.043) and V/S-ratio (P=.003). In multivariate-analysis clinical stage, HER-2 positivity and V/S-ratio were found to have statistically effect on pathological response. VAT-volume (P<.001), VAT-SUV (P=.016), SAT-volume (P<.001) and SAT-SUV (P<.001) has positive correlation with BMI value. On the other hand, V/S-ratio (P=.039) and SAT-density (P=.003) has negative correlation with BMI.
Metabolic activity of AT is associated with BMI and effected chemotherapy responses. LowV/S ratio was associated with high BMI and poor pathological response to NAC. V/S ratio may be a useful marker for the prediction of NAC responses.
La respuesta histopatológica a la quimioterapia neoadyuvante (NAC) es esencial en pacientes con cáncer de mama. La predicción de la respuesta histopatológica a la NAC en pacientes con cáncer de mama localmente avanzado es esencial para una estrategia de tratamiento óptima. El enfoque actual del tratamiento adyuvante o neoadyuvante se basa en el subtipo molecular. La obesidad puede afectar la respuesta a la quimioterapia. El objetivo de este estudio es: Evaluar la relación entre la actividad metabólica del tejido adiposo (AT) y la respuesta histopatológica de la NAC. Definir, la asociación del índice de masa corporal (IMC) y el valor del “Standard Uptake Value” (SUV) de AT medido por tomografía por emisión de positrones (PET/TC) con la respuesta a la quimioterapia neoadyuvante.
Hemos incluido ciento dieciséis pacientes consecutivos con cáncer de mama, estadio II y III, que acudieron para la realización de un PET/TC previo a NAC entre 2016 y 2020 Hemos calculado los parámetros metabólicos del tejido adiposo visceral (SUV del VAT), del tejido adiposo subcutáneo (SUV del SAT) y la relación entre ambos (relación V/S). Todos estos biomarcadores los hemos relacionado con la respuesta histopatológica de los pacientes.
El análisis univariante muestra una correlación significativa entre la respuesta histopatológica yel estadio clínico (P<,001), HER2 positivo (P<,001), SUV del VAT (P=,037), densidad del VAT (P=,043) y la relación V/S (P=,003). El análisis multivariante muestra una significación estadística entre HER2 positivo y la relación V/S con la respuesta histopatológica. Se evidencia una correlación positiva del IMC con el volumen del IVA (P<,001), SUV del IVA (P<,016), volumen del SAT (P<,001) y el SUV del SAT (P<,001). Se evidencia una correlación negativa del IMC con la relación V/S (P=,039) y la densidad del SAT (P=,003).
La actividad metabólica de AT se correlaciona con el IMC y la respuesta a la quimioterapia. La relación V/S baja se asocia a IMC alto y mal pronóstico, por lo que puede ser un marcador útil en la predicción de la respuesta a la NAC en pacientes con cáncer de mama localmente avanzado.
Objective
Cytokines have been the mainstay of treatment in metastatic renal cell cancer (mRCC) for decades before the introduction of tyrosine kinase inhibitors (TKIs), which dramatically changed the ...therapeutic landscape in these patients. This observational study was designed to evaluate use of TKIs in the treatment of cytokine-intolerant mRCC patients.
Methods
A total of 151 cytokine-intolerant mRCC patients who were treated with TKIs (sunitinib, pazopanib and sorafenib) were enrolled in this prospective, non-interventional, multi-center observational study at 16 oncology centers across Turkey. Mean (SD) age was 61.3 (11.1) years and 74.8% were males. Data on duration of TKI treatment was the primary outcome measure. Additionally, overall response rate (ORR), progression free survival (PFS), overall survival (OS) and safety data were recorded.
Results
Median duration of treatment was 8.2 months at a median follow up of 17.9 months. ORR and disease control rate were 12.5% and 70.8%, respectively. Median PFS and OS were 7.5 months (95%CI: 6.4–10.4) and 27.3 months (95%CI: 17.6–27.3) with no significant difference among three TKI agents in terms of treatment duration, ORR, PFS and OS. The most common adverse events excluding progression-which was the protocol requirement were diarrhea (13.6%), asthenia (13.6%) and hand-foot syndrome (12.6%). Dose modifications were required in 30.5% of the patients and 15% discontinued TKIs because of toxicity.
Conclusions
Our findings confirm the efficacy and safety profile of TKIs in the first-line treatment of mRCC patients intolerant to cytokine treatment. There was no significant difference among three TKI agents in terms of treatment duration, ORR, PFS and OS.
Trial registration: TURCOS ClinicalTrials.gov Identifier: NCT01585974. Registered April 25, 2012.
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