Follicular Lymphoma in Chile in the Adult Public Cancer Program: The Impact of Chemoimmunotherapy.

BACKGROUND: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma (NHL) in the United States and Europe. However, data on FL from Latin America are scant. AIMS: This study aims at better understand the clinical features, treatment patterns and outcomes of patients with FL in Chile. Of special interest was to evaluate POD24 as an adverse marker. METHODS AND RESULTS: We collected retrospective data from 722 patients 15 years or older diagnosed with FL and treated in 17 cancer centers in Chile between 2000 and 2019. Time to first treatment (TTFT), progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional-hazard regression models were fitted to investigate prognostic factor. The median age at diagnosis was 62 with a female predominance (63%); 73% of patients had advance stage disease and 68% had bone marrow involvement; 63% had intermediate or high FLIPI scores. The 1-year TTFT rate was 96%, and 30% of patients received chemoimmunotherapy. Adding rituximab to chemotherapy was associated with a higher complete response (69% vs. 60%; p < 0.001) and superior median OS (16 vs. 8 years; p < 0.001). Patients who experience POD24 had an inferior median OS (2.4 vs. 15 years). CONCLUSION: Our study shows a female predominance in patients with FL in Chile and confirms superior response and survival outcomes with adding rituximab to chemotherapy. Our study also confirms a poor OS in patients who experience POD24.

Fulvestrant en la práctica clínica: análisis de efectividad en pacientes uruguayas con cáncer de mama HR+/HER2. / Fulvestrant in clinical practice: Effectiveness analysis in Uruguayan patients with HR+/HER2- breast cancer.

Introduction: Fulvestrant demonstrated benefits in overall survival and progression-free survival in patients with advanced breast cancer, who are hormone receptor-positive and human epidermal growth factor receptor 2 negative. The characteristics, evolution, and survival of patients with hormone receptor-positive, HER2-negative breast cancer treated with fulvestrant were evaluated according to the national treatment coverage protocols of the National Resources Fund, with the aim of understanding the efficacy of fulvestrant in patients treated in usual clinical practice and comparing our results with those from pivotal studies. Methods: A database from the National Resources Fund covering the period from 2009 to 2022 was used. Survival curves were assessed using the Kaplan-Meier method, and differences were analyzed using the Log-Rank test. Results: A total of 1085 patients with an average age of 63,66 years were included. Following a follow-up of 14 months, the median overall survival was 16 months, and the median progression-free survival was 6 months. The presence of liver and bone metastases was associated with a shorter overall survival. Patients from the public sector and those with a better performance status experienced longer overall survival. Conclusions: Our findings provide a valuable perspective for treatment management in a context of limited resources. Overall survival and progression-free survival were somewhat lower than those reported in pivotal clinical trials. The presence of liver and bone metastases was associated with worse prognosis and survival; additionally, patients with worse performance status had shorter overall survival. These findings underscore the need for personalized therapies, opening new lines of future research.

Introducción: Fulvestrant demostró beneficio en sobrevida global y sobrevida libre de progresión en pacientes con cáncer de mama avanzado, con receptores hormonales positivos y receptor de factor de crecimiento epidérmico humano 2 negativo. Se evaluaron las características, la evolución y la sobrevida de pacientes con cáncer de mama receptor hormonal positivo, HER2 negativo, tratadas con fulvestrant, de acuerdo con los protocolos nacionales de cobertura de tratamiento del Fondo Nacional de Recursos. Su objetivo fue conocer la eficacia de fulvestrant en pacientes tratados en la práctica clínica habitual. Se compararon los resultados obtenidos en el presente trabajo con los resultados de los estudios pivotales. Métodos: Se utilizó la base de datos del Fondo Nacional de Recursos, que abarca el período de 2009 a 2022. La evaluación de las curvas de sobrevida se realizó mediante el método Kaplan-Meier y las diferencias se analizaron utilizando el test de Log-Rank. Resultados: Se incluyeron 1085 pacientes con una edad media de 63,66 años. Tras un seguimiento de 14 meses, la mediana de la sobrevida global fue de 16 meses y la de la sobrevida libre de progresión de 6 meses. La presencia de metástasis hepáticas y óseas se asoció con una menor sobrevida global. Los pacientes del sector público y aquellos con una mejor escala de estado funcional experimentaron una mayor sobrevida global. Conclusiones: Los resultados obtenidos ofrecen una perspectiva valiosa para la gestión de tratamientos en un contexto de recursos limitados. La sobrevida global y la sobrevida libre de progresión fueron algo inferiores a los reportados en los ensayos clínicos pivotales. La presencia de metástasis hepáticas y óseas se asoció a un peor pronóstico y una peor sobrevida. Además, los pacientes con peor escala de estado funcional tuvieron una menor sobrevida global. Estos hallazgos subrayan la necesidad de terapias personalizadas, abriendo nuevas líneas de investigación futura.

Determining Clinicopathologic Factors That Influence Treatment in Advanced Breast Cancer in Argentina After CDK4/6 Inhibitors.

PURPOSE: The optimal treatment sequence for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) after progression on first-line cyclin-dependent kinase 4/6 inhibitor (CDKi) and endocrine therapy is unclear. Clinical and biological factors influencing treatment choices and outcomes in the second-line setting need to be elucidated. MATERIALS AND METHODS: This is a retrospective analysis of a real-world cohort including patients with HR+/HER2- ABC who received CDKi and endocrine therapy in the first-line setting and progressed, requiring second-line treatment. Clinical and biological factors were analyzed to evaluate their association with daily treatment decisions and the prognostic role of progression-free survival (PFS) in the second-line setting. RESULTS: Two hundred thirty-five patients were included. Second-line treatments were hormone therapy (HT) based in 60% and chemotherapy based in 40% of patients. The second-line median PFS was 6.6 months, with no difference between treatment types. In multivariable analysis, postmenopausal status, lower Ki-67 expression, and non-de novo stage IV disease were associated with improved second-line (2L) PFS. Menopausal status significantly interacted with treatment type, with reduced PFS in premenopausal patients receiving HT-based treatments (4.7 v 8.7 months, P = .00045). CONCLUSION: In our study, treatment decisions reflected the current algorithm incorporated in our clinical guidelines, and prior treatment response was the most relevant factor to determine 2L treatment decision. Menopausal status interacted with the subsequent therapy efficacy in this setting. Hence, we consider that menopausal status should be routinely evaluated in the subgroup analysis of clinical trials.

Patterns and outcomes in HR+/HER2- advanced/metastatic breast cancer patients in Brazil receiving palbociclib.

Aim: To outline the demographic and clinical features, treatment approaches and clinical outcomes of patients treated with palbociclib as the initial therapy for HR+/HER2- advanced or metastatic breast cancer (aBC/mBC) in private healthcare facilities in Brazil.Materials & methods: This study involved a retrospective review conducted from June 2022 to May 2023.Results: The study included 121 patients, with an average age of 54.4 years, and 82 (67.7%) were menopausal at the time of diagnosis. Of these, 51 patients (42.1%) were treated with palbociclib and fulvestrant, while 67 patients (55.8%) received palbociclib and aromatase inhibitors. Most patients (65.3%) did not need to adjust their doses. The progression-free survival rates were 78% at 6 months and 60% at 12 months. Overall survival rates were 86% at 6 months and 70% at 12 months.Conclusion: Palbociclib combinations show promising effectiveness in managing HR+/HER2- advanced or metastatic breast cancer.

Treatment & results in Brazilian women with advanced or metastatic breast cancer given palbociclibBreast cancer is a major health issue worldwide, and it is the most common cancer among women in Brazil, with death rates on the rise. A significant portion of breast cancer cases are hormone receptor-positive (HR+) and HER2-negative (HER2-), making targeted treatments essential. One such treatment is palbociclib, a medication that inhibits Cyclin-dependent kinase 4 and 6 (CDK4/6), enzymes important in cell division. Clinical trials such as PALOMA-1, PALOMA-2 and PALOMA-3 have shown that palbociclib can help patients with advanced or metastatic HR+/HER2- breast cancer live longer without their disease getting worse. Studies in real-world settings around the world have confirmed these benefits, evaluating how well the treatment works over time. Palbociclib was approved for use in Brazil in 2018. This study looks back at the records of women treated with palbociclib in private healthcare settings in the country. It aims to provide crucial information which can help guide future treatment decisions.

Measurable Residual Disease and Clinical Outcomes in Chronic Lymphocytic Leukemia: A Systematic Review and Meta-Analysis.

Importance: Measurable residual disease (MRD) refers to the presence of disease at low levels not detected by conventional pathologic analysis. The association of MRD status as a surrogate end point of clinical outcome in chronic lymphocytic leukemia (CLL) has not been established in the era of targeted agents. Assessing the association of MRD with progression-free survival (PFS) may improve its role as a surrogate marker and allow its use to accelerate drug development. Objective: To assess the association between MRD and PFS in CLL using data from prospective clinical trials that studied targeted agents or obinutuzumab-based treatment. Data Sources: Clinical studies on CLL were identified via searches of PubMed, Embase, Scopus, and Web of Science from inception through July 31, 2023. Study Selection: Prospective, single-arm, and randomized clinical trials that assessed targeted agents or obinutuzumab-based treatment and reported PFS by MRD status were included. Studies with insufficient description of MRD information were excluded. Data Extraction and Synthesis: Study sample size, median patient age, median follow-up time, line of treatment, MRD detection method and time points, and survival outcomes were extracted. Main Outcomes and Measures: Analyses of survival probabilities and hazard ratios (HRs) were conducted for PFS according to MRD status. Meta-analyses were performed using a random-effects model. Results: A total of 11 prospective clinical trials (9 randomized and 2 nonrandomized) including 2765 patients were analyzed. Achieving undetectable MRD (uMRD) at 0.01% was associated with an HR of 0.28 (95% CI, 0.20-0.39; P < .001) for PFS. Median PFS was not reached in both groups (uMRD vs MRD), but the estimated 24-month PFS was better in the uMRD group (91.9% [95% CI, 88.8%-95.2%] vs 75.3% [95% CI, 64.7%-87.6%]; P < .001). The association of uMRD with PFS was observed in subgroup analyses in the first-line treatment setting (HR, 0.24; 95% CI, 0.18-0.33), relapsed or refractory disease setting (HR, 0.34; 95% CI, 0.16-0.71), and trials using time-limited therapy (HR, 0.28; 95% CI, 0.19-0.40). Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that assessing MRD status as an end point in clinical trials and as a surrogate of PFS may improve trial efficiency and potentially allow for accelerated drug registration.

Clinical Features and Therapeutic Outcomes Comparing Primary Mediastinal Large B-cell Lymphoma to Mediastinal Hodgkin Disease.

Currently, there is limited data available comparing Primary Mediastinal Large B-cell Lymphoma (PMBL) and mediastinal Hodgkin disease, nodular sclerosis type (HDNS). This is a retrospective cohort study that compares the clinical features, histology through immunohistochemistry (IHC) and treatment outcomes of 19 cases of PMBL and 39 cases of HDNS diagnosed over 13 years at a single institution in San Juan, PR. Superior Vena Cava syndrome (SVCS) and elevated Lactate Dehydrogenase (LDH) levels were more frequently seen in the PMBL cohort. At the median follow-up visit, of 74 months, no significant difference was seen in overall survival or progression free survival between PMBL and HDNS. Almost all of the relapses in the PMBL group occurred within 12 months of diagnosis. Our data suggests that PMBL and HDNS differ in their clinical presentation and have a favorable prognosis.

Trifluridine-tipiracil plus bevacizumab versus trifluridine-tipiracil monotherapy for chemorefractory metastatic colorectal cancer: a systematic review and meta-analysis.

Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy based on 5-fluorouracil. However, treatment following progression on the first and second line is still unclear. We searched PubMed, Scopus, Cochrane, and Web of Science databases for studies investigating the use of trifluridine-tipiracil with bevacizumab versus trifluridine-tipiracil alone for mCRC. We used RStudio version 4.2.3; and we considered p < 0.05 significant. Seven studies and 1,182 patients were included - 602 (51%) received trifluridine-tipiracil plus bevacizumab. Compared with control, the progression-free survival (PFS) (HR 0.52; 95% CI 0.42-0.63; p < 0.001) and overall survival (OS) (HR 0.61; 95% CI 0.52-0.70; p < 0.001) were significantly higher with bevacizumab. The objective response rate (ORR) (RR 3.14; 95% CI 1.51-6.51; p = 0.002) and disease control rate (DCR) (RR 1.66; 95% CI 1.28-2.16; p = 0.0001) favored the intervention. Regarding adverse events, the intervention had a higher rate of neutropenia (RR 1.38; 95% CI 1.19-1.59; p = 0.00001), whereas the monotherapy group had a higher risk of anemia (RR 0.60; 95% CI 0.44-0.82; p = 0.001). Our results support that the addition of bevacizumab is associated with a significant benefit in PFS, OS, ORR and DCR.

Effectiveness of dose-intensified salvage regimens versus standard-dose chemotherapy for progression-free survival in early progressed follicular lymphoma before autologous stem cell transplantation: a systematic review protocol.

OBJECTIVE: This review will evaluate the effectiveness of dose-intensified versus standard-dose salvage regimens on progression-free survival in early progressed follicular lymphoma before high-dose chemotherapy and autologous stem cell transplantation. INTRODUCTION: Despite the substantial advances in the management of follicular lymphoma, approximately 20% of patients experience progression of the disease within 2 years of induction therapy. These patients have worse outcomes, and autologous stem cell transplantation has been shown to improve outcomes in this context. Little is known about the optimal salvage regimen. INCLUSION CRITERIA: Studies must include patients ≥18 years old with early progressed follicular lymphoma who were submitted to autologous stem cell transplantation in subsequent remission. Clinical trials and observational studies will be included. METHODS: The search strategy will be carried out in MEDLINE (PubMed), Embase (Periódicos CAPES), Scopus, Web of Science, LiLACS, and the Cochrane Library. No date or language restrictions will be imposed. The recommended JBI approach to critical appraisal, study selection, data extraction, and data synthesis will be used. Studies should score at least 50% in accordance with the critical appraisal tool. Data will be pooled whenever possible using the random effects model. Heterogeneity will be assessed using the standard χ 2 and I2 tests. A funnel plot will be generated to assess publication bias if there are 10 or more studies included in the meta-analysis. The GRADE approach will be used to rate certainty of evidence. REVIEW REGISTRATION: PROSPERO CRD42022373345.

Comparative effectiveness of first-line systemic treatments for metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis.

OBJECTIVES: No head-to-head trials had been performed to estimate the relative effectiveness of poly ADP-ribose polymerase inhibitor (PARPi) and androgen receptor signaling inhibitor (ARSi) in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC). We aimed to perform a systematic review and network meta-analysis to evaluate the comparative effectiveness of various systemic treatment agents for patients with mCRPC. METHODS: A comprehensive literature search was conducted for abstracts and full-text articles from the database's inception through April 27, 2023. The study concentrated on assessing radiographic progression-free survival (rPFS) for both overall and homologous recombination repair mutation (HRRm) population, with overall survival (OS) as the secondary measure. Under the Bayesian framework, the overall effect was pooled using the fixed-effects model in base case analysis. Scenario analysis using restricted mean survival time (RMST) methods was performed to test the robustness of the results. RESULTS: Nine studies with 6,830 patients and 8 unique treatment options were included. Network meta-analysis demonstrated that talazoparib in combination with enzalutamide (TALA + ENZA; overall population, hazard ratio [HR], 0.20; 95% credible interval [CrI]: 0.16-0.26; RMST, 3.51; 95% confidence interval [CI] 2.46-4.60; HRRm population, HR, 0.15; 95% CrI: 0.09-0.23; RMST, 4.14; 95% CI 2.84-5.39) was superior to other treatments in the first-line setting in terms of rPFS. The results of Bayesian framework and RMST models showed consistent efficacy ranks. When extrapolated to overall survival benefit, within the Bayesian framework, olaparib plus abiraterone acetate and prednisone (OLAP + AAP) achieved the highest OS benefit for the overall population, which was not statistically significant when compared to TALA + ENZA. However, TALA + ENZA achieved the highest OS benefit at 3 years by applying RMST. CONCLUSIONS: We suggest that talazoparib in combination with enzalutamide is probably a preferred treatment agent for the overall population and HRRm patients with mCRPC. Given the limitations of network framework and the modeling assumptions undertaken to finalize the analyses, results should be cautiously interpreted.

Ten years' real-life experience on the use of multikinase inhibitors in patients with advanced differentiated thyroid cancer.

PURPOSE: To evaluate objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) associated with tyrosine kinase inhibitors (TKIs) in patients with radioiodine refractory differentiated thyroid cancer (RR-DTC). Additionally, to compare: (i) ORR and PFS among patients treated with lenvatinib and sorafenib; (ii) ORR and PFS among patients receiving lenvatinib as first-line vs. second-line and; (iii) adverse effects (AEs) observed in patients treated with these medications. METHODS: Retrospective analysis of RR-DTC adult patients treated with TKIs at the Division of Endocrinology, Hospital de Clinicas, University of Buenos Aires (March 2011-November 2023). RESULTS: Among 43 patients included in the study, 32 received sorafenib (30 as first-line and 2 as second-line), while 29 received lenvatinib (12 as first-line and 17 as second-line). The median PFS and OS for the entire cohort were 32.7 and 39.0 months, respectively. Lenvatinib demonstrated a significantly higher ORR compared to sorafenib (37.9% vs. 9.4%, p = 0.008). However, both drugs exhibited similar median PFS (23.2 vs. 16.0 months, p = 0.419). No significant difference was observed in ORR and PFS between patients receiving first-line vs. second-line lenvatinib. Sorafenib-treated patients experienced higher rates of hand-foot skin syndrome (69% vs. 41%, p = 0.032) and alopecia (25% vs. 3%, p = 0.018), whereas lenvatinib-treated patients had higher rates of proteinuria (31% vs. 0%, p < 0.001) and grade 3 hypertension (31% vs. 9%, p = 0.034). CONCLUSION: TKIs demonstrated efficacy and tolerability comparable to real-world data in RR-DTC. PFS was not statistically different between sorafenib and lenvatinib. Our study will help guide physicians in making informed decisions regarding treatment sequencing with TKIs in these patients.

Exploration of efficacy of different therapy regimens for advanced NSCLC patients with KRAS mutation in the first-line treatment.

PURPOSE: The treatment of the advanced non-small cell lung cancer (NSCLC) with KRAS mutation has been closely paid more attention. The aim of this study is to investigate the efficacy of different first-line regimens in advanced KRAS-mutated non-small cell lung cancer. METHODS: In our retrospective study, we collected patients with advanced NSCLC with KRAS mutation in Zhejiang Cancer Hospital between January 2015 and May 2023. We analyzed the benefit of different first-line therapy according to theraputic methods and the differential effect of the same treatment method among KRAS-mutated subtypes. We divided the patients into group A (A1, chemotherapy alone; A2, immunotherapy alone) and group B (B1, chemotherapy plus immunotherapy; B2, chemotherapy combined with antiangiogenic therapy; B3, chemotherapy combined with immunotherapy plus antiangiogenic therapy). The Kaplan-Meier survival curve was used to reflect the PFS and OS of different methods. The objective response rate (ORR) and the disease control rate (DCR) were used to evaluated the response. RESULTS: We enrolled 227 patients including eighty-two with KRAS G12C mutation. The ORR and DCR of first-line treatment in the overall population were 32.2% and 80.6% respectively. The median PFS was 6.7 months and the median OS was 17.4 months for the overall population. The PFS of the Group B was significantly better than that of the Group A (7.7 months vs 5.4 months, P = 0.003), while no significant difference in OS was observed (19.4 months vs 15.0 months, P = 0.077). In the Group B, chemotherapy combined immunotherapy with antiangiogenic therapy showed better PFS than chemotherapy plus immunotherapy (14.1 months vs 7.7 months, P = 0.049), and OS also showed that tendency of difference (31.9 months vs 19.3 months, P = 0.158). There was no statistically significant difference between KRAS G12C and non-G12C mutation according to first-line treatment methods, whereas patients with TP53 co-mutation showed a better survival benefit (OS, 23.7 vs 12.5 months, P = 0.023). CONCLUSION: In the first-line treatment, combination regimen has advantages over single regimen. Among them, chemotherapy combined with immunotherapy plus antiangiogenic therapy can achieve significant efficacy benefits.

Efficacy and safety analysis of immunotherapy in non-small cell lung cancer patients with MET alterations.

BACKGROUND: Mesenchymal epithelial transition factor (MET) is a rare oncologic driver gene, and information on immunotherapy for non-small cell lung cancer (NSCLC) patients with this driver gene is limited. Here we evaluate the efficacy and safety of immune checkpoint inhibitors (ICI) under different therapeutic regimen for NSCLC patients with MET alterations. METHODS: From June 2019 to December 2023, we assessed the efficacy and toxicity of ICIs in 42 NSCLC patients with MET alterations. Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. We assessed the size of target lesion according to RECIST v1.1, and objective response rate (ORR) was defined as the sum of complete response (CR) and partial response (PR), disease control rate (DCR) as the sum of CR, PR, and disease stable. RESULTS: A total of 42 NSCLC patients with MET alterations were included in this retrospective study, 10 was MET 14 skipping mutation and 32 was MET amplification. The ORR for ICI treatment was 30.95% and the DCR was 71.43%. Median progression-free survival (mPFS) and median overall survival (OS) were 4.40 and 13.97 months, respectively. There exists statistical differences between the mPFS of ICI monotherapy and combine ICI therapy (2.8 vs 7.8 months, p = 0.022). The incidence of drug-related adverse reactions was 47.62%, mainly bone marrow suppression (14.28%), immune-related pneumonia (7.14%), and liver function impairment (7.14%), and six patients (14.28%) experiencing grade 3 or above adverse events. CONCLUSION: NSCLC patients with MET alterations can benefit from immunotherapy, especially the patients treated by combined ICI therapy. However, special attention should be paid to the occurrence of grade 3/4 adverse reactions while using the combined ICI therapy.

Peripheral NK cells identified as the predictor of response in extensive-stage small cell lung cancer patients treated with first-line immunotherapy plus chemotherapy.

PURPOSE: Although immunotherapy improves outcomes in extensive-stage small-cell lung cancer (ES-SCLC), the search for biomarkers predicting treatment success is crucial. Natural killer (NK) cells are potential indicators in various cancers, however, their precise role in ES-SCLC prognosis remains unclear. METHODS: In this retrospective study, 33 patients with ES-SCLC treated with first-line immuno-chemotherapy were enrolled. The peripheral NK cell percentage and its longitudinal dynamics were analyzed using flow cytometry. Progression-free survival (PFS) and overall survival (OS) were calculated as hazard ratio (HR) and compared statistically. RESULTS: The median PFS was better in the group with normal baseline NK cell levels than the low group (7.0 vs. 4.6 months; HR = 0.17; 95% CI 0.07-0.41; P < 0.0001), but there was no association with OS (14.9 vs. 10.3 months; HR = 0.55; 95% CI 0.23-1.31; P = 0.171). Furthermore, the NK cell% for 95.0% of patients increased after immunochemotherapy in the clinical response group (P = 0.0047), which led to a better median PFS (6.3 vs. 2.1 months; HR = 0.23; 95% CI 0.05-0.98; P < 0.0001) and OS (14.9 vs. 5.9 months; HR = 0.20; 95% CI 0.04-1.02; P < 0.0001). Similar trends were observed with NK cell% changes up to disease progression, improving PFS (6.5 vs. 4.3; HR = 0.41; 95% CI 0.12-0.92; P = 0.0049) and OS (17.4 vs. 9.7; HR = 0.42; 95% CI 0.17-1.02; P < 0.0001). CONCLUSION: In patients with ES-SCLC, the percentage and changes in peripheral NK cells can predict the response to combined immunotherapy and chemotherapy.

Comparison of efficacy and safety of PD-1/PD-L1 combination therapy in first-line treatment of advanced NSCLC: an updated systematic review and network meta-analysis.

BACKGROUND: The use of immune checkpoint inhibitors has led to an increase in randomized controlled trials exploring various first-line combination treatment regimens. With the introduction of new PD-1/PD-L1 inhibitors, there are now more clinical options available. For the first time, the AK105 monoclonal antibody Penpulimab, developed in China, was included. The AK105-302 Phase III trial studied the efficacy and safety of Penpulimab combined with chemotherapy in patients with advanced or metastatic squamous NSCLC. To determine the optimal treatment options, we conducted an updated network meta-analysis to compare the effectiveness and safety of these regimens. METHODS: The system retrieves data from Chinese and English electronic databases, Clinical Trials, and the gov Clinical Trial Registration website up to September 6, 2023. The study indirectly compared the efficacy and safety of PD-1/PD-L1 combination regimens, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), all-grade adverse events, and above-grade III adverse events. Subgroup analyses were conducted based on programmed death ligand 1 (PD-L1) level, histological type, ECOG score, sex, and smoking history. RESULTS: Nineteen RCTS were included, with a total of ten thousand eight hundred patients. Penpulimab plus chemotherapy (Pen + CT) provided the best OS (HR = 0.55, 95% CI 0.38-0.81) for PD-L1 patients with non-selective advanced NSCLC. Except Nivolumab plus Ipilimumab (Niv + Ipi), other PD-1/PD-L1 combination therapies significantly extended PFS compared with CT, and Nivolumab plus Bevacizumab combined with chemotherapy (Niv + Bev + CT) (HR = 0.43, 95% CI 0.26-0.74) provided the best PFS benefit and was comparable to Pen + CT (HR = 1.0) for PFS prolongation. For ORR, except Niv + Ipi, all the other regimens significantly improved ORR compared with CT. In terms of safety, except Tor + CT, the incidence of any-grade AEs or grade ≥ 3 adverse events may be higher than those of chemotherapy. The subgroup analysis revealed that for patients with PD-L1 levels below 1%, treatment with Tor + CT resulted in the best progression-free survival (HR = 0.47, 95% CI 0.25-0.86). For patients with PD-L1 levels of 1% or higher, Sintilimab plus chemotherapy (Sin + CT) (HR = 0.56, 95% CI 0.31-0.99) and Camrelizumab plus chemotherapy (Cam + CT) (HR = 0.43, 95% CI 0.28-0.64) were associated with the best overall survival and progression-free survival, respectively. For patients with SqNSCLC, combined immunotherapy may provide greater survival benefits. For patients with Non-sqNSCLC, Niv + Bev + CT and Tor + CT were associated with optimal PFS and OS, respectively. Cam + CT provided the best PFS in male patients with a history of smoking and an ECOG score of 0. In both female and non-smoking patient subgroups, Pem + CT was associated with the best PFS and OS benefits. CONCLUSION: For patients with advanced non-selective PD-L1 NSCLC, two effective regimens are Pen + CT and Niv + Bev + CT, which rank first in OS and PFS among all patients. Cam + CT and Tor + CT have advantages for OS in patients with SqNSCLC and Non-sqNSCLC, respectively. Niv + Ipi + CT provided the best OS benefit for patients with an ECOG score of 0, while Pem + CT may be the most effective treatment for patients with an ECOG score of 1. Pem + CT has a better effect on female patients and non-smokers. Sin + CT was found to be the most effective treatment for male patients and the smoking subgroup, while Cam + CT was found to be the most effective for PFS. In addition, Tor + CT was associated with the best PFS for patients with negative PD-L1 expression. Pem + CT was found to significantly improve both PFS and OS compared to CT alone. For patients with positive PD-L1 expression, Sin + CT and Cam + CT were found to be optimal for OS and PFS, respectively. It is important to note that, with the exception of Tor + CT, the toxicity of the other combinations was higher than that of CT alone.

Clinical features and treatment outcomes of PD-1 inhibitor therapy in elderly patients (≥ 65 years) with advanced esophageal squamous cell carcinoma: a real-world study.

PURPOSE: This study aims to determine the clinical features and outcomes of PD-1 inhibitor therapy as the initial treatment in patients aged 65 years or older with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: The retrospective study conducted a comprehensive analysis of elder patients diagnosed with locally advanced or metastatic ESCC who underwent combined immunochemotherapy in the first affiliated hospital of Nanchang University from January 2019 to January 2023. The main efficacy measures were the objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints were disease control rate (DCR) and overall survival (OS). The evaluation of safety was based on the assessment of adverse events (AEs). RESULTS: A total of 88 patients were enrolled in the study. All patients received PD-1 inhibitors combined with chemotherapy including taxane and platinum as the first-line treatment. The median PFS was 6.2 months (95% CI: 5.1-7.3), and the median OS was 15.3 months (95% CI: 12.9-17.7). The ORR and DCR were 42.0% and 72.7%, correspondingly. 68 (77.3%) patients experienced treatment-related adverse events (TRAEs) of various degrees, with neutrophil count decreased (21, 23.9%) being the most frequent. TRAEs of grade 3 or 4 occurred in 13 (14.8%) patients. CONCLUSION: The study demonstrated that individuals older than 65 years with locally advanced or metastatic ESCC have a survival benefit from the first-line treatment of PD-1 inhibitors combined therapy, with a manageable safety profile.

Efficacy and safety of a combination treatment of immune checkpoint inhibitors in metastatic breast cancer: a systematic review and meta-analysis.

PURPOSE: Immune checkpoint inhibitors (ICIs) in combination with chemotherapy have showed its benefits in clinical studies, and here we conducted a further evaluation on the safety and efficacy of this treatment strategy. METHODS: A systematic literature review was conducted in PubMed, Embase and Cochrane Library to identify clinical studies on ICIs and chemotherapy for metastatic breast cancer. The primary efficacy endpoints were progression-free survival (PFS) and overall survival (OS), and adverse events (AEs) were analyzed. Random or fixed effects models were used to estimate pooled Hazard ratio (HR), odds ratio (OR) and the data of 95% confidence interval (CI) depend on the Heterogeneity. Cochrane risk assessment tool was used to assess risk of bias. We also drew forest plots and funnel plots, respectively. RESULTS: Seven studies with intend-to-treat (ITT) population for 3255 patients were analyzed. ICIs pooled therapy showed clinical benefits compared with chemotherapy alone, improving PFS (HR = 0.81, 95% CI: 0.74-0.90) of patients with metastatic triple negative breast cancer (mTNBC), especially in patients with PD-L1-positive tumors. However, it had no effect on OS (HR = 0.92, 95% CI 0.85-1.01). Besides, mTNBC patients received pooled therapy were less frequently to have AEs (OR = 1.30, 95% CI: 1.09-1.54). In patients with metastatic Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer, pooled therapy showed no benefit for PFS (HR = 0.80, 95% CI: 0.50-1.28) and OS (HR = 0.87, 95% CI: 0.48-1.58). CONCLUSION: Pooled therapy had improved PFS in mTNBC patients, especially in patients with PD-L1-positive tumors, and it was less likely to cause grade ≥ 3 AEs.

Clinical difference on the variants and co-mutation in a Chinese cohort with ALK-positive advanced non-small cell lung cancer.

PURPOSE: Despite the generally favourable prognoses observed in patients with ALK-positive non-small cell lung cancer (NSCLC), there remains significant variability in clinical outcomes. The objective of this study is to enhance patient stratification by examining both the specific sites of gene fusion and the presence of co-occurring mutations. METHODS: We collected retrospective clinical and pathological data on ALK-positive patients with locally advanced or metastatic disease. ALK fusion variants and concomitant mutations were identified through next-generation sequencing technology. We then assessed treatment efficacy via tumor response and survival metrics. RESULTS: This study included a total of 59 patients, with 49 harboring echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusions and 10 presenting with rare fusions. The median follow-up period was 33 months. Clinical outcomes between non-EML4-ALK and EML4-ALK patients were comparable. Among the EML4-ALK cohort, patients with longer variants (v1, v2, v8) demonstrated superior progression-free survival (PFS) (median PFS: 34 months vs. 11 months; hazard ratio [HR]: 2.28; P = 0.05) compared to those with shorter variants (v3, v5). Furthermore, patients treated with second-generation ALK inhibitors (ALKi) displayed a progression-free survival advantage (median PFS: not reached [NR] vs. 9 months; HR: 5.37; P = 0.013). Baseline TP53 co-mutation were linked with a substantially shorter OS (median OS,37 months vs. NR; HR 2.74; P = 0.047). CONCLUSIONS: In ALK+ NSCLC, longer EML4-ALK variants correlate with improved prognosis and enhanced response to second-generation ALKi, while TP53 co-mutations indicate a negative prognosis.

Hypertension as predictive factor for bevacizumab-containing first-line therapy in metastatic breast and colorectal cancer in BRECOL (GEICAM/2011-04) study.

BACKGROUND: Retrospective data suggest an association between bevacizumab efficacy and the incidence of arterial hypertension (AHT). Additionally, epigenetic mechanisms have been related to AHT. METHODS: This prospective observational study conducted by GEICAM Spanish Breast Cancer Research Group included metastatic breast (MBC) or colorectal (mCRC) cancer patients treated with bevacizumab-containing chemotherapy as first-line treatment. Blood pressure (BP) levels were measured (conventional and 24-h Holter monitoring) at baseline and up to cycle 3. Primary endpoint assessed BP levels increase as predictive factor for progression-free survival (PFS). Germline DNA methylation profile was explored in pre-treatment blood samples; principal component analysis was used to define an epigenetic predictive score for increased BP levels. RESULTS: From Oct-2012 to Jul-2016, 143 (78 MBC and 65 mCRC) patients were included. The incidence of AHT according to guidelines was neither predictive of PFS nor of best overall tumor response (BOR). No statistically significant association was observed with systolic BP nor diastolic BP increment for PFS or BOR. Grade 3 and 4 adverse events were observed in 37 and 5% of patients, respectively. We identified 27 sites which baseline methylation status was significantly associated to BP levels increase secondary to bevacizumab-containing chemotherapy. CONCLUSIONS: Neither the frequency of AHT nor the increase of BP levels were predictive of efficacy in MBC and mCRC patients treated with bevacizumab-containing chemotherapy. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT01733628.

Effect of immune checkpoint inhibitors at different treatment time periods on prognosis of patients with extensive-stage small-cell lung cancer.

BACKGROUND: The application of immune checkpoint inhibitors (ICIs) in treating patients with extensive-stage small-cell lung cancer (ES-SCLC) has brought us new hope, but the real-world outcome is relatively lacking. Our aim was to investigate the clinical use, efficacy, and survival benefit of ICIs in ES-SCLC from real-world data analysis. METHODS: A retrospective analysis of ES-SCLC patients was conducted between 2012 and 2022. Progression-free survival (PFS) and overall survival (OS) were assessed between groups to evaluate the value of ICIs at different lines of treatment. PFS1 was defined as the duration from initial therapy to disease progression or death. PFS2 was defined as the duration from the first disease progression to the second disease progression or death. RESULTS: One hundred and eighty patients with ES-SCLC were included. We performed landmark analysis, which showed that compared to the second-line and subsequent-lines ICIs-combined therapy group (2SL-ICIs) and non-ICIs group, the first-line ICIs-combined therapy group (1L-ICIs) prolonged OS and PFS1. There was a trend toward prolonged OS in the 2SL-ICIs group than in the non-ICIs group, but the significance threshold was not met (median OS 11.94 months vs. 11.10 months, P = 0.14). A longer PFS2 was present in the 2SL-ICIs group than in the non-ICIs group (median PFS2 4.13 months vs. 2.60 months, P < 0.001). CONCLUSION: First-line ICIs plus chemotherapy should be applied in clinical practice. If patients did not use ICIs plus chemotherapy in first-line therapy, the use of ICIs in the second line or subsequent lines of treatment could prolong PFS2.

MET overexpression correlated with prognosis of EGFR-mutant treatment­naïve advanced lung adenocarcinoma: a real­world retrospective study.

BACKGROUND: About 50-60% treatment-naïve advanced non-small-cell lung cancers were coexistence of epidermal growth factor receptor (EGFR) and mesenchymal epithelial transition (MET) overexpression. However, few studies demonstrated the prognostic value of MET protein expression in untreated EGFR-mutant lung adenocarcinoma (LUAD). METHODS: A total of 235 EGFR-mutant untreated advanced LUAD patients were retrospectively enrolled. MET expression was determined using immunohistochemistry, and MET positivity was defined as 2 + or 3 + using the METmab scoring algorithm. Progression-free survival (PFS) and overall survival (OS) were analysed according to MET expression status. Independent factors predicting prognosis were identified using multivariate Cox regression analyses. RESULTS: Of the 235 patients, 113 (48.1%) harboured exon 19 deletion (19_del), 103 (43.8%) had exon 21 L858R mutations, and 19 (8.1%) had other mutation types, including exon 21 L861Q, exon 18 G719A/C, exon 20 S768I, and L858R/19_del double mutations. MET-positive expression was observed in 192 (81.7%) cases. There was no significant difference in baseline clinicopathological characteristics between MET positivity and MET negativity groups. Patients were stratified by different EGFR mutation subtypes. MET-positive patients in the L858R mutation subgroup had markedly shorter PFS and OS than MET-negative patients (median PFS: 13 versus 27.5 months, p < 0.001; median OS: 29 versus not reached, p = 0.008), but no significant difference was observed in the 19_del subgroup. Multivariate Cox regression analyses indicated that MET positivity was an independent predictor for poor PFS and OS in L858R subgroup (PFS: HR = 3.059, 95% CI 1.552-6.029, p = 0.001; OS: HR = 3.511, 95% CI 1.346-9.160, p = 0.010). Additionally, an inferior survival outcome of MET positivity was observed in the L858R mutation subgroup when treated with EGFR-tyrosine kinase inhibitor (TKI) monotherapy as the first-line regimen (median PFS: 13 versus 36.5 months, p < 0.001; median OS: 29 versus not reached, p = 0.012) but not with EGFR-TKI plus platinum doublet chemotherapy. CONCLUSIONS: MET positive expression was an independent predictor of poor outcomes in untreated EGFR L858R mutation advanced LUAD patients treated with first-line EGFR-TKI monotherapy.