RESUMEN

PURPOSE: This retrospective real-world study compared overall survival (OS) between patients with BRCA wild-type (BRCAwt) recurrent epithelial ovarian cancer (OC) who received niraparib second-line maintenance (2LM) versus active surveillance (AS) using target trial emulation, cloning, inverse probability of censoring weighting (IPCW) methodology to minimize immortal time bias. METHODS: Eligible patients from a United States-based, deidentified, electronic health record-derived database were diagnosed with epithelial OC (January 1, 2011-May 31, 2021), were BRCAwt, and completed second-line (2L) therapy (January 1, 2017-March 2, 2022). Patient data were cloned at index (2L last treatment date), assigned to niraparib 2LM and AS cohorts, and censored when treatment deviated from clone assignment. Follow-up was measured from index to earliest of study end (May 31, 2022), last activity, or death. Median OS (mOS) and hazard ratios were estimated from stabilized IPCW Kaplan-Meier curves and Cox regression models. RESULTS: Overall, 199 patients received niraparib 2LM, and 707 had their care managed with AS. Key characteristics were balanced across cohorts after cloning and stabilized IPCW. Median follow-up was 15.6- and 9.3-months pre-cloning. IPCW mOS was 24.1 months (95% CI: 20.9-29.5) and 18.4 months (95% CI: 15.1-22.8) in niraparib 2LM and AS cohorts, respectively (hazard ratio, 0.77; 95% CI: 0.66-0.89). CONCLUSIONS: This real-world study provides supportive evidence of an OS benefit for patients with BRCAwt recurrent OC who received 2LM niraparib monotherapy compared with those whose care was managed with AS. The analytic strategies implemented were useful in minimizing immortal time bias and measured confounding.

Asunto(s)

Indazoles , Recurrencia Local de Neoplasia , Neoplasias Ováricas , Piperidinas , Humanos , Femenino , Piperidinas/uso terapéutico , Piperidinas/administración & dosificación , Indazoles/uso terapéutico , Indazoles/administración & dosificación , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/mortalidad , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/mortalidad , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Adulto , Espera Vigilante , Estados Unidos/epidemiología , Quimioterapia de Mantención/métodos , Bases de Datos Factuales

RESUMEN

BACKGROUND: The addition of trabectedin to doxorubicin, followed by trabectedin maintenance, may have superior efficacy to doxorubicin alone as first-line treatment in patients with advanced leiomyosarcoma. METHODS: We conducted a phase 3 trial involving patients with metastatic or unresectable leiomyosarcoma who had not received chemotherapy previously. Patients were randomly assigned to receive either single-agent doxorubicin (six cycles) or doxorubicin plus trabectedin (six cycles), with continued trabectedin as maintenance therapy in patients in the doxorubicin-trabectedin group who did not have disease progression. Surgery to resect residual disease was allowed in each group after six cycles of therapy. Analyses of progression-free survival (primary end point) and overall survival (secondary end point) were adjusted for two stratification factors: tumor origin site (uterine vs. soft tissue) and disease stage (locally advanced vs. metastatic). The primary end-point results were reported previously. RESULTS: A total of 150 patients underwent randomization. At a median follow-up of 55 months (interquartile range, 49 to 63), a total of 107 patients had died (47 in the doxorubicin-trabectedin group and 60 in the doxorubicin group). The median overall survival was longer in the doxorubicin-trabectedin group (33 months; 95% confidence interval [CI], 26 to 48) than in the doxorubicin group (24 months; 95% CI, 19 to 31); the adjusted hazard ratio for death was 0.65 (95% CI, 0.44 to 0.95). In a finding consistent with earlier reports, progression-free survival was longer in the doxorubicin-trabectedin group (12 months; 95% CI, 10 to 16) than in the doxorubicin group (6 months; 95% CI, 4 to 7); the adjusted hazard ratio for progression or death was 0.37 (95% CI, 0.26 to 0.53). The incidence of adverse events and the percentage of patients with dose reductions were higher with doxorubicin plus trabectedin than with doxorubicin alone. CONCLUSIONS: Combination therapy with doxorubicin and trabectedin induction, followed by trabectedin maintenance, was associated with improved overall survival and progression-free survival, as compared with doxorubicin alone, among patients with metastatic or surgically unresectable uterine or soft-tissue leiomyosarcoma. (Funded by PharmaMar and others; LMS04 ClinicalTrials.gov number, NCT02997358.).

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Doxorrubicina , Leiomiosarcoma , Neoplasias de los Tejidos Blandos , Trabectedina , Neoplasias Uterinas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Estimación de Kaplan-Meier , Leiomiosarcoma/tratamiento farmacológico , Leiomiosarcoma/mortalidad , Leiomiosarcoma/patología , Quimioterapia de Mantención , Supervivencia sin Progresión , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/patología , Análisis de Supervivencia , Trabectedina/administración & dosificación , Trabectedina/efectos adversos , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/mortalidad , Neoplasias Uterinas/patología , Estadificación de Neoplasias

Asunto(s)

Recurrencia Local de Neoplasia , Neoplasias Ováricas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Humanos , Femenino , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Quimioterapia de Mantención

RESUMEN

Objective: This study aims to explore the survival advantages of different maintenance strategies for MCL. Methods: Clinical data of 693 newly diagnosed MCL patients in multi-centers admitted from April 1999 to December 2019 were collected. 309 cases received maintenance treatment. The characteristics of patients in different maintenance treatment groups were summarized and Kaplan-Meier survival and prognosis analysis were conducted. Results: The overall 3-year and 5-year progression-free survival (PFS) rates were (73.5±2.9) % and (53.6±4.3) %, respectively. The 3-year and 5-year overall survival (OS) rates were (94.2±1.5) % and (82.7±3.2) %, respectively. The clinical features of different maintenance treatment groups were generally consistent. The 3-year PFS rates of rituximab maintenance, lenalidomide maintenance, BTK inhibitor maintenance and dual-drug maintenance were (70.4±4.1) %, (69.1±7.6) %, (86.9±5.0) %, and (80.4±5.1) %, respectively. Corresponding 3-year OS rates were (92.9±2.4) %, (97.3±2.7) %, (97.9±2.1) %, and (95.3±2.7) %, respectively. There were no significant difference in different groups (P=0.632, 0.313). Survival analysis identified the MCL International Prognostic Index (MIPI) high-risk group and achieving complete remission before maintenance treatment as independent risk factors for PFS. The MIPI high-risk group, high-dose cytarabine application, treatment lines, and early disease progression (POD24) emerged as independent risk factors for OS. Conclusion: Comparing the different maintenance strategies of MCL, the result showed that BTK inhibitors (BTKi) maintenance demonstrated preliminary advantages in survival. Meanwhile, high-risk group according to MIPI and incomplete remission before maintenance treatment were significant factors related to disease progression.

Asunto(s)

Linfoma de Células del Manto , Rituximab , Humanos , Estudios Retrospectivos , Tasa de Supervivencia , Linfoma de Células del Manto/tratamiento farmacológico , Pronóstico , Rituximab/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Lenalidomida/administración & dosificación , Quimioterapia de Mantención , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Masculino , Femenino , Persona de Mediana Edad

RESUMEN

Although the significant strides in novel therapeutic approaches have prolonged the survival of multiple myeloma (MM) patients, the unfavorable prognosis of cytogenetically high-risk newly diagnosed MM (NDMM) remains intractable with the lack of consensus regarding the choice of maintenance regimens. Therefore, this study was initiated with the aim of examining the effectiveness of various maintenance treatments for this group of patients in jeopardy. Overall, 17 studies with 1937 high-risk NDMM patients were included in the network meta-analysis. Combination therapies involving novel drugs presented encouraging prospects in the maintenance phase, while the patients and circumstances for the application of different regimens still needed to be further distinguished and clarified. To investigate the current status of maintenance therapy of high-risk NDMM patients in clinical practice, a real-world cohort of high-risk NDMM was retrospectively incorporated 80 patients with lenalidomide maintenance and 53 patients with bortezomib maintenance, presenting the median PFS of 31.7 months and 30.4 months, respectively (p = 0.874, HR = 0.966, 95% CI: 0.628-1.486). Collectively, this study illuminated the present constraints of conventional approaches during the maintenance phase for high-risk NDMM patients while highlighting the future potential associated with enhanced regimens integrating novel medications.

Asunto(s)

Lenalidomida , Quimioterapia de Mantención , Mieloma Múltiple , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Humanos , Lenalidomida/uso terapéutico , Bortezomib/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Antineoplásicos/uso terapéutico , Resultado del Tratamiento

RESUMEN

BACKGROUND: Germline breast cancer susceptibility gene (gBRCA) mutation in patients with pancreatic cancer (PC) is not common in clinical practice. Therefore, factors that efficiently show gBRCA mutations and the real-world outcomes of olaparib maintenance therapy have not been fully established. In the present study, we clarified the indicators for the effective detection of gBRCA mutation and the efficacy and safety of olaparib as maintenance therapy. METHODS: We retrospectively analyzed 84 patients with PC who underwent gBRCA testing (BRACAnalysis, Myriad Genetics, Salt Lake City, UT, USA) at our institute between January 2021 and March 2022. For each patient, clinical data were extracted from medical records. RESULTS: The median patient age was 64 y (29-85 y), and 41 patients (48.8%) were male. The gBRCA mutations were identified in 10 (11.9%) patients; two patients had BRCA1 mutation and eight had BRCA2 mutation. All patients with gBRCA mutation had a family history of any cancer, and eight of them had a family history of Hereditary Breast and Ovarian Cancer syndrome (HBOC)-related cancer. The gBRCA mutation rate was higher for patients with PC with a family history of HBOC-related cancer compared to that in patients with PC having a family history of other cancers and no family history of cancer (22.9% vs. 4.1%; P = 0.014). In our study, eight out of 10 patients with gBRCA-positive PC received olaparib after platinum-based chemotherapy. The best responses to platinum-based chemotherapy included a complete response in one patient (12.5%) and a partial response in seven patients (87.5%). The median duration of treatment with platinum-based chemotherapy plus olaparib was 17.5 months (8-87 months), and the duration of treatment with olaparib maintenance therapy was 11 months (1-30 months). During olaparib maintenance therapy, three patients showed no disease progression. One of these three patients underwent conversion surgery after receiving olaparib for 12 months. CONCLUSIONS: The gBRCA testing should be considered proactively, especially in patients with PC with a family history of HBOC-related cancer.

Asunto(s)

Proteína BRCA1 , Proteína BRCA2 , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Neoplasias Pancreáticas , Ftalazinas , Piperazinas , Humanos , Ftalazinas/uso terapéutico , Persona de Mediana Edad , Femenino , Anciano , Masculino , Adulto , Estudios Retrospectivos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/tratamiento farmacológico , Anciano de 80 o más Años , Piperazinas/uso terapéutico , Piperazinas/administración & dosificación , Proteína BRCA2/genética , Proteína BRCA1/genética , Quimioterapia de Mantención , Pruebas Genéticas/métodos , Relevancia Clínica

Asunto(s)

Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Humanos , Acrilamidas/uso terapéutico , Compuestos de Anilina/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Indoles , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Estadificación de Neoplasias , Piperazinas/uso terapéutico , Pirimidinas , Nivel de Atención , Quimioterapia de Mantención/métodos , Quimioterapia de Mantención/normas

RESUMEN

INTRODUCTION: Evidence on the comparative efficacy and safety of approved therapies for ulcerative colitis (UC) during induction and maintenance, including upadacitinib (UPA), vedolizumab (VEDO), ustekinumab (UST), and tofacitinib (TOFA), is limited. METHODS: Using data from phase 3 trials, three placebo (PBO)-anchored matching-adjusted indirect comparisons of the efficacy and safety of UPA versus VEDO, UST, and TOFA (U-ACHIEVE and U-ACCOMPLISH, GEMINI-1, UNIFI, and OCTAVE induction and maintenance trials) have been conducted. Baseline characteristics from UPA trials were weighted separately to match each comparator trial. Induction responders were re-randomized to oral UPA 15 or 30 mg, VEDO 300 mg intravenously every 8 weeks (Q8W), UST 90 mg SC Q8W, or oral TOFA 5 mg, or PBO in maintenance. Treat-through efficacy outcomes at weeks 44(UST)/46(VEDO)/52(UPA/TOFA) were adjusted by the likelihood of induction response and included clinical response, clinical remission, and endoscopic improvement. Safety outcomes included adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation (except UPA vs. VEDO). Benefit-risk was assessed by numbers needed to treat (NNT)/harm, calculated as the inverse of the difference in proportions of patients achieving each efficacy/safety outcome for UPA versus comparator. RESULTS: The proportions of patients who demonstrated clinical response or endoscopic improvement was greater with UPA 15 mg versus VEDO and TOFA (p < 0.05). The proportions of patients demonstrating all treat-through efficacy outcomes were significantly greater with UPA 30 mg versus VEDO, UST, or TOFA with NNTs 3.2-8.7. No significant differences in proportions of AEs, SAEs, and AEs leading to discontinuation were observed between the two doses of UPA and comparators. CONCLUSION: In patients with active UC, greater clinical efficacy, and similar safety after 1 year of maintenance were observed with UPA versus VEDO, UST, and TOFA, suggesting a favorable benefit-risk profile for UPA. Despite matched baseline characteristics, differences in trial design and endpoints may persist.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Colitis Ulcerosa , Compuestos Heterocíclicos con 3 Anillos , Piperidinas , Pirimidinas , Ustekinumab , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Piperidinas/uso terapéutico , Piperidinas/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Masculino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Femenino , Adulto , Persona de Mediana Edad , Ustekinumab/uso terapéutico , Resultado del Tratamiento , Fármacos Gastrointestinales/uso terapéutico , Fármacos Gastrointestinales/efectos adversos , Pirroles/uso terapéutico , Pirroles/efectos adversos , Pirroles/administración & dosificación , Quimioterapia de Mantención/métodos

RESUMEN

OBJECTIVE: We aimed to evaluate the efficacy of decitabine consolidation after treatment with CD19/CD22 chimeric antigen receptor T-cell (CAR-T) for patients with relapsed/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL). METHODS: We retrospectively analysed 48 patients with r/r B-ALL who received CD19/CD22 CAR-T therapy between September 2017 and May 2021. Sixteen patients received decitabine consolidation (20 mg/m2/day for 5 days at 3-month intervals) after CAR-T therapy (DAC group), while 32 patients did not receive decitabine consolidation (CON group). Overall survival (OS), leukaemia-free survival (LFS), and cumulative incidence of relapse (CIR) were evaluated in both groups. Time-to-event analysis was performed using the Kaplan-Meier method. RESULTS: The median follow-up periods in the DAC and CON groups were 41.2 months and 28.6 months, respectively. The 4-year OS and 4-year LFS rates in both groups were 93.3 % and 64.3 % (P=0.029) and 87.5 % and 55.9 % (P=0.059), respectively. The 1-year CIR was 6.25 % and 28.6 %, respectively. Univariate and multivariate Cox regression analyses showed that decitabine consolidation after CAR-T therapy was significantly associated with superior OS (hazard ratio [HR]: 0.121, 95 % confidence interval [CI]: 0.015-0.947, P=0.044), and bridging to haematopoietic stem cell transplantation after CAR-T therapy was significantly associated with superior LFS (HR: 0.279, 95 %CI: 0.093-0.840, P=0.023). CONCLUSIONS: Our study recommends decitabine consolidation after CD19/CD22 CAR-T therapy as a novel maintenance strategy to improve the survival outcomes of patients with r/r B-ALL.

Asunto(s)

Antígenos CD19 , Decitabina , Inmunoterapia Adoptiva , Lectina 2 Similar a Ig de Unión al Ácido Siálico , Humanos , Decitabina/uso terapéutico , Decitabina/administración & dosificación , Femenino , Masculino , Inmunoterapia Adoptiva/métodos , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Adolescente , Antígenos CD19/inmunología , Lectina 2 Similar a Ig de Unión al Ácido Siálico/inmunología , Adulto Joven , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Antimetabolitos Antineoplásicos/uso terapéutico , Tasa de Supervivencia , Quimioterapia de Consolidación , Estudios de Seguimiento , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/terapia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Receptores Quiméricos de Antígenos/inmunología , Niño , Quimioterapia de Mantención , Anciano

RESUMEN

BACKGROUND: A few prospective cohort studies support the safety of switching from intravenous to subcutaneous administration of vedolizumab during maintenance therapy in patients with inflammatory bowel disease. Real-life data on switching after intravenous induction therapy are lacking. OBJECTIVE: The aim was to obtain real-world data on subcutaneous vedolizumab treatment in patients with inflammatory bowel disease after switching from intravenous vedolizumab induction or maintenance therapy, and to evaluate treatment persistence, safety, and changes in disease activity and serum vedolizumab concentrations. METHODS: We performed a retrospective registry-based study of inflammatory bowel disease patients who received subcutaneous vedolizumab therapy in two tertiary centres. RESULTS: Altogether, 103 patients (26 Crohn's disease and 77 ulcerative colitis) switching from intravenous maintenance therapy (group 1) and 44 patients (14 and 30, respectively) switching from intravenous induction therapy (group 2) were included. At 6 months from baseline, 90.3% of the patients in group 1 and 90.9% of the patients in group 2 continued on subcutaneous vedolizumab. After the switch in group 1, disease activity remained stable. In group 2, clinical disease activity decreased significantly in ulcerative colitis patients ( P  = 0.002). The median serum vedolizumab concentration was 34.00 µg/ml during subcutaneous maintenance therapy in group 1, which was significantly higher than the median concentration during intravenous therapy (17.00 µg/ml, P  < 0.001), but remained unchanged in group 2 after the switch (31.50 µg/ml). CONCLUSION: Based on these data, subcutaneous vedolizumab treatment is well-tolerated and the treatment persistence remains high after switching from intravenous to subcutaneous vedolizumab therapy.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Colitis Ulcerosa , Enfermedad de Crohn , Fármacos Gastrointestinales , Quimioterapia de Mantención , Sistema de Registros , Humanos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Femenino , Masculino , Adulto , Estudios Retrospectivos , Colitis Ulcerosa/tratamiento farmacológico , Fármacos Gastrointestinales/administración & dosificación , Fármacos Gastrointestinales/sangre , Fármacos Gastrointestinales/uso terapéutico , Fármacos Gastrointestinales/farmacocinética , Persona de Mediana Edad , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/sangre , Inyecciones Subcutáneas , Resultado del Tratamiento , Sustitución de Medicamentos , Infusiones Intravenosas , Administración Intravenosa , Adulto Joven , Factores de Tiempo

RESUMEN

OBJECTIVES: Patterns of disease recurrence on poly(ADP-ribose) polymerase inhibitor maintenance therapy are unclear and may affect subsequent treatment. This ad hoc subgroup analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 study evaluated patterns of initial recurrence in patients with advanced ovarian cancer (AOC). METHODS: PRIMA included participants at high risk for disease progression. This ad hoc analysis only evaluated participants randomized to niraparib maintenance without evidence of disease at baseline. The number and site(s) of initial recurrent lesions at investigator-assessed progressive disease (PD) were evaluated. RESULTS: Of the 314 niraparib-treated patients analyzed, 190 developed ≥1 new lesion (median number of new lesions, 1.0; interquartile range, 1-2). In total, 93.2% (177/190) of patients developed 1-3 lesions at first disease progression. The most common sites of recurrence were the peritoneum (30.0% [57/190]), lymph nodes (26.3% [50/190]), and liver (20.5% [39/190]). Similar results were observed when patients with PD were stratified by biomarker status, disease stage at diagnosis, and type of debulking surgery. Patients with homologous recombination-proficient tumors, stage III disease, or a history of primary debulking developed a median of 2.0 new lesions at first progression; patients with homologous recombination-deficient tumors, stage IV disease, or a history of interval debulking developed a median of 1.0 new lesion. CONCLUSIONS: Many patients with AOC without lesions at first-line maintenance treatment initiation develop oligometastatic disease at first recurrence. Prospective evaluation is required to determine whether these patients have improved outcomes when local therapies are combined with continuous, systemic, targeted maintenance therapy.

Asunto(s)

Indazoles , Quimioterapia de Mantención , Recurrencia Local de Neoplasia , Neoplasias Ováricas , Piperidinas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Humanos , Femenino , Indazoles/administración & dosificación , Indazoles/uso terapéutico , Piperidinas/administración & dosificación , Piperidinas/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Persona de Mediana Edad , Anciano , Quimioterapia de Mantención/métodos , Adulto , Ftalazinas/administración & dosificación , Ftalazinas/efectos adversos , Ftalazinas/uso terapéutico , Progresión de la Enfermedad

RESUMEN

Platinum-based chemotherapy has been the cornerstone of first-line treatment for advanced urothelial carcinoma for decades, based on its proven efficacy and well-characterized safety profile. Although enfortumab vedotin (EV) plus pembrolizumab showed superior efficacy versus platinum-based chemotherapy in the EV-302 phase 3 trial, common and potentially cumulative toxicities associated with EV plus pembrolizumab may make this combination less suitable for some patients, such as those with pre-existing neuropathy, hyperglycemia, or hepatic impairment, or patients likely to have favorable outcomes with platinum-based chemotherapy. The availability of EV plus pembrolizumab in various countries may also be limited by financial considerations. Thus, platinum-based chemotherapy is likely to remain a valuable option for advanced urothelial carcinoma. Eligibility for cisplatin- or carboplatin-based regimens can be determined by assessing renal function, performance status, and specific comorbidities. In cisplatin-eligible and -ineligible patients without disease progression following platinum-based chemotherapy, avelumab first-line maintenance is standard of care based on findings from the JAVELIN Bladder 100 phase 3 trial, which showed that avelumab first-line maintenance plus best supportive care prolonged overall survival and progression-free survival compared with best supportive care alone across clinically relevant subgroups. Adverse events associated with avelumab were generally consistent with those observed with other immune checkpoint inhibitors, and long-term follow-up showed no new safety concerns with prolonged treatment. Efficacy benefits and safety profiles were similar in patients who received avelumab first-line maintenance after cisplatin- or carboplatin-based chemotherapy. The effectiveness and safety of avelumab first-line maintenance have been confirmed in several real-world studies. Overall, these data support the use of avelumab first-line maintenance for all platinum-treated patients without disease progression. In this podcast, we discuss the evolving role of platinum-based chemotherapy in this disease setting in the context of EV-302 trial results and describe practical considerations in patients receiving first-line cisplatin- or carboplatin-based chemotherapy followed by avelumab maintenance therapy.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatino , Carcinoma de Células Transicionales , Cisplatino , Humanos , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/mortalidad , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Quimioterapia de Mantención/métodos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/mortalidad

RESUMEN

PURPOSE: To explore safety and tolerability parameters for the niraparib individualized starting dose (ISD) in patients with newly diagnosed advanced ovarian cancer that responded to platinum-based chemotherapy who participated in the phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial (NCT02655016). METHODS: The PRIMA protocol was amended so newly enrolled patients received an ISD based on baseline body weight/platelet count. In this ad hoc analysis, the timing, duration, and resolution of the first occurrence of common any-grade hematologic (thrombocytopenia, anemia, neutropenia) and nonhematologic (nausea, asthenia/fatigue, constipation, insomnia, hypertension) treatment-emergent adverse events (TEAEs) were evaluated by treatment arm in the ISD safety population (data cutoff, November 17, 2021; median follow-up, 3.5 years). RESULTS: Of 733 randomized patients, 255 were enrolled after the ISD protocol amendment and received ≥ 1 dose of study treatment (niraparib, 169; placebo, 86). In the niraparib arm, median times to first events were 22.0-35.0 days for hematologic TEAEs and 7.0-56.0 days for nonhematologic TEAEs. First events resolved in ≥ 89.8% of patients for hematologic TEAEs; for nonhematologic TEAEs, resolution rates ranged from 55.3% (insomnia) to 86.0% (nausea). Median durations of first hematologic TEAEs were ≤ 16.0 days, but for first nonhematologic TEAEs ranged from 18.0 days (nausea) to 134.0 days (insomnia). CONCLUSION: The niraparib ISD was generally well tolerated and TEAEs were manageable. Common hematologic and nonhematologic TEAEs occurred early and first events of hematologic TEAEs had a short duration (≈ 2 weeks) and a high resolution rate. These findings support close monitoring immediately following niraparib initiation and may help inform patient expectations for niraparib safety.

Asunto(s)

Indazoles , Neoplasias Ováricas , Piperidinas , Humanos , Femenino , Indazoles/efectos adversos , Indazoles/administración & dosificación , Piperidinas/administración & dosificación , Piperidinas/efectos adversos , Piperidinas/uso terapéutico , Persona de Mediana Edad , Anciano , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Isoquinolinas/administración & dosificación , Isoquinolinas/efectos adversos , Isoquinolinas/uso terapéutico , Quimioterapia de Mantención

Asunto(s)

Anticuerpos Biespecíficos , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Anticuerpos Biespecíficos/uso terapéutico , Femenino , Masculino , Adulto , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Persona de Mediana Edad , Trasplante Homólogo , Adulto Joven , Quimioterapia de Mantención , Adolescente , Antineoplásicos/uso terapéutico , Resultado del Tratamiento , Anciano

RESUMEN

PURPOSE: Continuous lenalidomide maintenance treatment after autologous stem cell transplantation delivers improvement in progression free and overall survival among newly diagnosed multiple myeloma patients and has been the standard of care in the UK since March 2021. However, there is scant information about its impact on patients' day-to-day lives. This service evaluation aimed to qualitatively assess patients receiving lenalidomide treatment at a cancer centre in London, in order that the service might better align with needs and expectations of patients. METHODS: We conducted 20 semi-structured interviews among myeloma patients who were on continuous lenalidomide maintenance treatment at a specialist cancer centre in London. Members of the clinical team identified potentially eligible participants to take part, and convenience sampling was used to select 10 male and 10 female patients, median age of 58 (range, 45-71). The median treatment duration was 11 months (range, 1-60 months). Participants were qualitatively interviewed following the same semi-structured interview guide, which was designed to explore patient experience and insights of lenalidomide. Reflexive thematic analysis was used for data analysis. RESULTS: Four overarching themes were as follows: (i) lenalidomide: understanding its role and rationale; (ii) reframing the loss of a treatment-free period to a return to normal life; (iii) the reality of being on lenalidomide: balancing hopes with hurdles; (iv) gratitude and grievances: exploring mixed perceptions of care and communication. Results will be used to enhance clinical services by tailoring communication to better meet patients' preferences when making treatment decisions. CONCLUSION: This study highlights that most patients feel gratitude for being offered continuous lenalidomide and perceive it as alleviating some fears concerning relapse. It reveals variations in side effects in different age groups; younger patients reported no/negligible side effects, whilst several older patients with comorbidities described significant symptom burden, occasionally leading to treatment discontinuation which caused distress at the perceived loss of prolonged remission. Future research should prioritise understanding the unique needs of younger patients living with multiple myeloma.

Asunto(s)

Lenalidomida , Mieloma Múltiple , Investigación Cualitativa , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/psicología , Mieloma Múltiple/terapia , Lenalidomida/uso terapéutico , Lenalidomida/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Anciano , Londres , Quimioterapia de Mantención/métodos , Entrevistas como Asunto , Calidad de Vida , Trasplante Autólogo/métodos , Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación

Asunto(s)

Carcinoma de Células Transicionales , Supervivencia sin Progresión , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia de Mantención , Adulto , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/patología

RESUMEN

INTRODUCTION: Despite the prognosis of patients affected by acute myeloid leukemia (AML) improved in the last decade, most patients relapse. Maintenance therapy after a chemotherapy approach with or without allogeneic stem cell transplantation could be a way to control the undetectable residual burden of leukemic cells. Several studies are being carried out as maintenance therapy in AML. Some critical points need to be defined, how the physician can choose among the various drugs available. AREAS COVERED: This review discusses the advances and controversies surrounding maintenance therapy for AML patients. EXPERT OPINION: Patients withFLT3-positive AML should receive midostaurin or quizartinib in the first-linesetting. For a patient initially receiving midostaurin, consider switching to sorafenib in the post-transplant setting. Because of the improved safety profile and potency, many experts will lean toward using a second-generation FLT3 inhibitor such as quizartinib or gilteritinib. Finally, no data indicate whether maintenance therapy should be prolonged until progression or for a defined period.

Asunto(s)

Leucemia Mieloide Aguda , Quimioterapia de Mantención , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/tratamiento farmacológico , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Tirosina Quinasa 3 Similar a fms/metabolismo , Trasplante de Células Madre Hematopoyéticas , Estaurosporina/análogos & derivados , Estaurosporina/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Antineoplásicos/uso terapéutico , Sorafenib/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Compuestos de Anilina , Pirazinas , Benzotiazoles

RESUMEN

BACKGROUND: Maintenance therapy could significantly improve the prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy. Anlotinib is effective, tolerable, and convenient in administration as a third-line treatment for NSCLC. This study aimed to evaluate the efficacy and safety of maintenance therapy with anlotinib after platinum-based induction chemotherapy for patients with advanced NSCLC. METHODS: This pooled analysis of 2 multicenter, open-label, single-arm, phase 2 clinical trials (ALTER-L014 and ALTER-L011) enrolled patients with locally advanced or metastatic NSCLC and without known sensitive mutations in China between September 2018 and January 2021. The primary outcome was progression-free survival. The secondary outcomes were objective response rate, disease control rate, overall survival, and safety. RESULTS: The data of 23 patients were pooled, with 15 from ALTER-L014 and 8 from ALTER-L011. At the cutoff date of June 13, 2021, the median progression-free survival since the start of maintenance therapy was 5.95 (95% confidence interval, 4.30-8.80) months. Nineteen patients had stable disease, 1 had a partial response and 3 had progressive disease. The objective response rate was 4.35%, while disease control rate was 86.96%. The median overall survival of the patients since the start of maintenance therapy was 18.60 (95% confidence interval, 6.87-22.80) months. The incidence of adverse events of grade ≥ 3 was 21.7%. CONCLUSION: Anlotinib might offer a new option for maintenance treatment in patients with locally advanced or metastatic NSCLC without known sensitive mutations after standard first-line platinum-based chemotherapy.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas , Indoles , Quimioterapia de Inducción , Neoplasias Pulmonares , Quinolinas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Indoles/uso terapéutico , Indoles/administración & dosificación , Indoles/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Femenino , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Anciano , Quimioterapia de Inducción/métodos , Quimioterapia de Mantención/métodos , Adulto , Supervivencia sin Progresión , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico

RESUMEN

OBJECTIVE: This study aimed to evaluate the clinical efficacy and safety of anlotinib as maintenance therapy in patients with advanced cholangiocarcinoma following first-line chemotherapy. METHODS: This retrospective study enrolled 154 patients with advanced biliary tract cancer admitted to the hospital between January 2020 and December 2022. All patients received first-line intravenous chemotherapy with gemcitabine combined with cisplatin, oxaliplatin, or tegafur. Among the 106 patients who achieved disease control, 47 received oral anlotinib hydrochloride (12 mg daily, 2 weeks on/1 week off) as maintenance therapy. Clinical efficacy, including ORR, DCR, DOR, PFS, and OS, was compared between the anlotinib maintenance and non-maintenance groups. Subgroup analysis based on NLR levels was also performed. RESULTS: Among the 47 anlotinib maintenance patients, the ORR was 21.28% and the DCR was 51.06%. The median DOR was 36 weeks, and the median PFS was 43 weeks in the anlotinib group, versus 28 weeks and 38 weeks in the non-maintenance group, respectively. The median OS was not reached in the anlotinib group but was 48 weeks in the non-maintenance group. Patients receiving anlotinib maintenance had significantly longer DOR, PFS, and OS (all p < 0.05). Patients with low NLR levels had better survival benefits from anlotinib. CONCLUSION: Maintenance therapy with anlotinib demonstrates potential efficacy and a reliable safety profile in patients with advanced cholangiocarcinoma following first-line treatment. The efficacy of anlotinib therapy appears to be influenced by NLR levels. Further validation with larger sample sizes is warranted to strengthen the robustness and reliability of the results.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de los Conductos Biliares , Colangiocarcinoma , Indoles , Linfocitos , Neutrófilos , Quinolinas , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Quinolinas/administración & dosificación , Quinolinas/uso terapéutico , Indoles/administración & dosificación , Indoles/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/sangre , Neutrófilos/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Linfocitos/patología , Tasa de Supervivencia , Pronóstico , Estudios de Seguimiento , Adulto , Quimioterapia de Mantención/métodos , Cisplatino/administración & dosificación , Oxaliplatino/administración & dosificación , Gemcitabina , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación

RESUMEN

BACKGROUND: Previous studies have reported that rituximab (RTX) therapy might be beneficial in reducing relapse rates in patients with IgG4-related disease (IgG4-RD). Therefore, we aimed to systematically assess the efficacy and safety of RTX induction treatment and the effect of RTX maintenance in patients with IgG4-RD. METHODS: The protocol was registered in the PROSPERO (CRD42023427352). PubMed, Embase, the Cochrane database, Scopus, and the Web of Science were interrogated to identify studies that evaluated the impact of RTX on prognosis in IgG4-RD. We explored the impact of various subgroups of factors on relapse outcomes and focused on the possible role of maintenance therapy in reducing relapse rates. The pooled incidence of adverse events of RTX therapy and the influencing factors have also been evaluated. RESULTS: Eighteen studies comprising 374 patients (mean age 56.0 ± 8.7 years; male 73.7 %) with a mean follow-up duration of 23.4 ± 16.3 months were included. The pooled estimate of the response rate, complete remission rate, overall relapse rate, adverse event rate, and serious adverse event rate of RTX induction therapy were 97.3 % (95 % CI, 94.7 %-99.1 %), 55.8 % (95 % CI, 39.6 %-71.3 %), 16.9 % (95 % CI, 8.7 %-27.1 %), 31.6 % (95 % CI, 16.7 %-48.9 %) and 3.9 % (95 % CI, 0.8 %-8.9 %), respectively. In subgroup analysis, the pooled relapse rate was significantly lower in studies with maintenance than without maintenance (2.8% vs 21.5 %, p < 0.01). Pooled Kaplan-Meier relapse curves also demonstrated that RTX maintenance therapy provided a better prognosis. CONCLUSIONS: RTX induction therapy appears to have satisfactory efficacy in the induction of remission in IgG4-RD. In addition, prophylactic RTX maintenance therapy after induction may be beneficial in preventing relapse of IgG4-RD.

Asunto(s)

Enfermedad Relacionada con Inmunoglobulina G4 , Factores Inmunológicos , Rituximab , Humanos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Enfermedad Relacionada con Inmunoglobulina G4/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Factores Inmunológicos/efectos adversos , Recurrencia , Resultado del Tratamiento , Quimioterapia de Mantención/métodos , Inducción de Remisión , Quimioterapia de Inducción