Real-world efficacy of chidamide plus R-CHOP in newly diagnosed double-expressor diffuse large B-cell lymphoma.

Background: Approximately 20%-30% of diffuse large B-cell lymphoma (DLBCL) cases are classified as double-expressor lymphoma (DEL), characterized by the co-expression of the MYC and BCL2 proteins. However, the most effective therapeutic strategy for DEL remains unidentified. Objectives: To evaluate the efficacy of a novel histone deacetylase inhibitor, chidamide, in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (CR-CHOP) in the treatment of DEL. Design: This was a retrospective study. Methods: This study included 62 DEL patients from December 2016 to December 2020. All patients were administered a first-line treatment with CR-CHOP. The short-term efficacy, survival status, and adverse reactions in this population were observed, and the prognostic factors were analyzed. Results: The median age was 53.9 years (range, 19-77). All patients received a median of six cycles (range, 1-8) of treatment, with 79.0% achieving complete response (CR) and an overall response rate of 88.7%. With a median follow-up of 45.5 months (range, 1-82), the median progression-free survival (PFS) and median overall survival (OS) had not yet been reached. However, the 3-year PFS rate was 71% (95% CI: 61-83), the 3-year OS rate was 87% (95% CI: 79-96), the 5-year PFS rate was 67% (95% CI: 55-80), and the 5-year OS rate was 85% (95% CI: 77-95). Age and autologous stem cell transplantation after CR or partial response were independent prognostic factors for PFS, while various clinical factors were not associated with OS outcomes. The most common grades 3-4 hematologic and nonhematologic toxicity were leukopenia (46.7%) and infection (21%), respectively. Conclusion: This long-term follow-up study indicates that CR-CHOP in untreated DLBCL with the DEL phenotype demonstrates high short-term efficacy and safety as well as promising survival outcomes.

Heterogeneity between subgroups of first-line chemoimmunotherapy for extensive-stage small cell lung cancer patients: a meta-analysis and systematic review.

Objectives: Differences in clinicopathological characteristics of extensive-stage small cell lung cancer (ES-SCLC) patients may influence the immune response. This study aims to evaluate the heterogeneity of response to first-line chemoimmunotherapy between subgroups in ES-SCLC to screen out suitable populations. Materials and methods: We searched the PubMed, EMBASE, and Cochrane Library databases from inception to December 3, 2022 for randomized controlled trials (RCTs) of ES-SCLC chemoimmunotherapy. We also reviewed main conferences from January 1, 2021 to October 1, 2023. A trial-specific hazard ratio (HR) ratio for each subgroup was calculated, and these ratios were then pooled using the deft approach. Results: A total of 9 RCTs with 4099 patients were finally included. The pooled ratios were 0.92 (95% CI = 0.77 to 1.09) for OS-HRs and 0.79 (95% CI = 0.55 to 1.13) for PFS-HRs in women versus men. The pooled ratios of OS-HRs and PFS-HRs in patients with positive versus negative PD-L1 expression were 1.26 (95% CI = 0.91 to 1.73) and 1.08 (95% CI = 0.77 to 1.52), respectively. The pooled ratios of OS-HRs and PFS-HRs in patients without versus with brain metastasis were 0.77 (95% CI = 0.59 to 1.01) and 0.71 (95% CI = 0.44 to 1.12). No statistically significant differences were also found in terms of subgroups for age, liver metastasis, smoking status, ECOG PS, LDH level, type of platinum salt and race. Conclusion: Women or patients with negative PD-L1 expression or with LDH ≤ ULN or without brain metastasis tend to benefit more from first-line chemoimmunotherapy in ES-SCLC. More trials are needed to prospectively validate the therapeutic heterogeneity among clinicopathological characteristics. Systematic review registration: https://inplasy.com/inplasy-2023-3-0064/ identifier, INPLASY202330064.

Diagnostic accuracy of active pulmonary tuberculosis screening during detention admission: a systematic review.

Individuals entering incarceration are at high risk for infectious diseases, other ill conditions, and risky behavior. Typically, the status of active pulmonary tuberculosis (PTB) is not known at the time of admission. Early detection and treatment are essential for effective TB control. So far, no study has compared the diagnostic accuracy of various TB screening tools in detention using a network meta-analysis (NMA). We aimed to investigate the diagnostic accuracy of active PTB screening tests upon detention admission. We searched PubMed, Global Index Medicus, the Cochrane Library electronic databases, and grey literature for publications reporting detention TB entry screening in March 2022 and January 2024. Inclusion was non-restrictive regarding time, language, location, reference standards, or screening tests. Eligible study designs comprised comparative, observational, and diagnostic studies. Publications had to report TB screening of individuals entering confinement and provide data for diagnostic accuracy calculations. The QUADAS-2 tool was designed to assess the quality of primary diagnostic accuracy studies. This systematic review was registered with PROSPERO (CRD42022307863) and conducted without external funding. We screened a total of 2,455 records. Despite extensive searching, no studies met our inclusion criteria. However, we identified evidence revealing key differences in screening algorithm application. In conclusion, more diagnostic accuracy data on TB screening algorithms for detention admission worldwide needs to be collected. We recommend that global TB initiatives set up multi-site studies to investigate the diagnostic accuracy of TB screening on admission in low- and high-prevalence criminal justice systems. Further network meta-analyses of these studies could inform policymakers and public health experts to establish or fine-tune TB control in detention settings.

FLAIR: A Phase II, Open Label, Randomized Study of Osimertinib Plus Bevacizumab Versus Osimertinib in Recurrent or Metastatic Treatment-Naïve NSCLC Patients Harboring EGFR 21L858R Mutation.

INTRODUCTION: Osimertinib, the 3rd generation EGFR-TKI, has emerged as standard first-line treatment for patients with advanced EGFR mutated nonsmall cell lung cancer (NSCLC). Patients with exon 21 L858R mutation showed lower efficacy with EGFR-TKIs than those with 19Del mutation, even with osimertinib, it remains an unmet medical need to further improve the efficacy in L858R population. We present the rationale and design for FLAIR (NCT04988607), which will investigate the efficacy and safety of osimertinib plus bevacizumab versus osimertinib monotherapy in treatment-naïve recurrent or metastatic NSCLC patients harboring EGFR exon 21 L858R mutation. MATERIALS AND METHODS: FLAIR is a prospective, multicenter, randomized, open label study, which is initiated by Chinese Thoracic Oncology Group (CTONG2002). Patients age ≥18 years with primary recurrent or metastatic nonsquamous NSCLC who are treatment-naïve with documented EGFR exon 21 L858R mutation is eligible. Patients will be randomized 1:1 to receive osimertinib 80 mg once daily plus bevacizumab 15mg/kg every 3 weeks or osimertinib monotherapy 80 mg once daily until progression or another discontinuation criterion is met. The primary endpoint is investigator-assessed progression free survival (PFS). Secondary endpoints include: overall survival rate at 24 months, time to treatment failure (TTF), overall response rate (ORR), disease control rate (DCR), duration of response (DoR), central nervous system (CNS) PFS, CNS ORR and safety. RESULTS: FLAIR has completed the enrollment, and results are expected in the fourth quarter of 2025 (depending on the actual event rate). CONCLUSIONS: This study will offer better perspectives on the efficacy and safety of osimertinib plus bevacizumab combination therapy in treatment-naïve recurrent or metastatic NSCLC patients harboring EGFR exon 21 L858R mutation, providing valuable guidance for clinical practice.

Systematic review and network meta-analysis of lorlatinib with comparison to other anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) as first-line treatment for ALK-positive advanced non-smallcell lung cancer (NSCLC).

BACKGROUND: Next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) (alectinib, brigatinib, and lorlatinib) demonstrate superior progression-free survival (PFS) over chemotherapy or crizotinib as first-line (1L) treatment of ALK-positive advanced non-smallcell lung cancer (NSCLC). METHODS: We conducted network meta-analyses (NMAs) comparing the relative efficacy of lorlatinib with other ALK TKIs in this indication. Evidence identified from a systematic literature review and subsequent updates formed the basis of our evidence. The primary analysis investigated PFS by independent review committee (IRC) in the intent-to-treat (ITT) population. Secondary outcomes included PFS among subgroups, intracranial time to progression (IC TTP), adverse events, and discontinuation due to adverse events. For each of the outcomes, Bayesian proportional hazards NMAs estimated the relative treatment effects. Additionally, we compared the design and results of eight published NMAs conducted for 1L ALK + advanced NSCLC to date. RESULTS: We formed a network of 10 trials, allowing indirect treatment comparisons. Two trials directly compared alectinib (600 mg twice daily) to crizotinib and one trial directly compared lorlatinib to crizotinib. The results of the NMA show that the hazard ratios (95 % credible interval [CrI]) for ITT PFS IRC were 0.61 (95 % CrI: 0.39, 0.97) when comparing lorlatinib with alectinib (600 mg twice daily) and 0.57 (95 % CrI: 0.35, 0.93) when comparing lorlatinib with brigatinib. In the review of published NMAs, HRs for lorlatinib versus alectinib (600 mg twice daily) and brigatinib were compared. This comparison confirmed that each published NMA yielded similar results. CONCLUSIONS: Our NMA analysis adds to existing findings and supplements data gaps from other published NMAs. Findings from eight published NMAs consistently supported lorlatinib as a clinically effective 1L treatment for ALK + advanced NSCLC patients compared to other TKIs.

Chemotherapy combined with regorafenib and immune checkpoint inhibitors as a first-line treatment for patients with advanced biliary tract cancer: a single arm phase II trial.

Objective: This study aimed to investigate the efficacy, long-term prognosis and safety of combining chemotherapy with regorafenib and immune checkpoint inhibitors as first-line treatment for patients with advanced biliary tract carcinoma (BTC). Methods: In this single arm phase II trial, twenty-nine patients with advanced BTC were included, all of whom received gemcitabine-based chemotherapy combined with regorafenib and immune checkpoint inhibitors as the first-line treatment. And the study analyzed anti-tumor efficacy, long-term prognosis, and adverse reactions. Results: Among the patients, 0 patient achieved complete response, 18 patients (62.1%) achieved partial response, 8 patients (27.6%) had stable disease, and 3 patients (10.3%) experienced progressive disease. The corresponding objective response rate (ORR) was 18/29 (62.1%), and the disease control rate (DCR) was 26/29 (89.7%). The median overall survival (OS) was 16.9 months (95% confidence interval [CI]: 12.0 -21.8) and the median progress free survival (PFS) was 10.2 months (95% CI: 7.8- 12.6). The 1-year OS and PFS were 65% (95% CI: 0.479-0.864) and 41% (95% CI: 0.234-0.656), respectively. The incidence of adverse reactions was 27/29 (93.1%), and the incidence of grade III/IV adverse reactions was 5/29 (17.2%). Conclusion: The combination of chemotherapy, regorafenib, and immune checkpoint inhibitors as a first-line treatment for patients with advanced BTC may has good anti-tumor efficacy without causing serious adverse reactions, and can significantly improve the long-term prognosis.

Efficacy and safety of the first-line systemic treatments in patients with advanced-stage urothelial carcinoma: a systematic review and network meta-analysis.

Introduction: In recent years, some clinical studies of first-line treatment for advanced-stage urothelial carcinoma (aUC) have reached the main endpoint, showing inconsistent clinical efficacy. We hope to explore the efficacy and safety of first-line treatment for aUC. Methods: The relevant literature from January 2000 to February 2024 was searched, and the R language (version 4.3.1) was used to perform a network meta-analysis based on the JAGS package and GEMTC package under the Bayesian framework. The main indicators included OS, PFS, ORR and adverse events of grade 3 or higher. This study has been registered in PROSPERO (CRD42024525372). Results: A total of 8 RCTs involving 5539 patients and 12 treatments were included. Pembrolizumab plus Enfortumab Vedotin (PEM+EV) was significantly better than other groups in OS, PFS and ORR. In terms of OS, PEM+EV was significantly better than nivolumab plus platinum-based chemotherapy (NIVO+platinumCT) (HR=0.60; 95% CI: 0.45-0.81), PEM+platinumCT (HR=0.55; 95%CI: 0.42-0.72), atezolizumab (ATE) + platinumCT (HR=0.57; 95%CI: 0.43-0.75) and platinumCT (HR=0.47; 95%CI: 0.38-0.58). In terms of PFS, PEM+EV was also significantly better than NIVO+platinumCT (HR=0.62; 95%CI: 0.48-0.82), PEM+platinumCT (HR=0.58; 95%CI: 0.45-0.74), ATE+platinumCT (HR=0.55; 95%CI: 0.43-0.69) and platinumCT (HR=0.45; 95%CI: 0.38-0.54). In terms of ORR, PEM+EV had a significant be nefit compared with other treatment measures, which was 2.63 times that of platinumCT (OR=2.63; 95%CI: 2.00-3.45). The adverse events of grade 3 or higher in immunotherapy (ATE, PEM, durvalumab) was significantly lower than other treatment measures. Conclusions: PEM+EV can significantly prolong OS and PFS compared with other treatments, and has a higher ORR. The adverse events of grade 3 or higher of ATE was the lowest. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024525372, identifier CRD42024525372.

Impact on survival benefits of asymptomatic primary tumor resection after bevacizumab plus FOLFIRI as first-line therapy for patients with metastatic colorectal cancer with synchronous unresectable metastasis.

BACKGROUND: Metastatic colorectal cancer (mCRC) poses a clinical challenge and requires a combination of systemic therapy and conversion surgery. Although first-line chemotherapy and targeted therapy are considered the standard treatments for mCRC, the role of primary tumor resection (PTR) in asymptomatic synchronous mCRC with unresectable metastatic lesion after initial therapy remains relatively underexplored. MATERIALS: A retrospective review was conducted from January 2015 to January 2021, involving 74 patients with synchronous mCRC who received bevacizumab plus FOFIRI as first-line systemic therapy. All 74 patients had unresectable metastatic lesions confirmed through multidisciplinary team discussion. Patient characteristics, PTR data, and radiotherapy (RT) and overall survival (OS) outcomes were analyzed. The patients were categorized into a "PTR" group and a "No PTR" group and then further stratified into "4A," "4B," and "4C" subgroups based on the initial mCRC stage. Additionally, four subgroups-namely "PTR( +)/RT( +)," "PTR( +)/RT( -)," "PTR( -)/RT( +)," and "PTR( -)/RT( -)"-were formed to assess the combined effects of PTR and RT. RESULTS: The median OS for all the patients was 23.8 months (20.5-27.1 months). The "PTR" group exhibited a significantly higher median OS of 25.9 months (21.3-30.5 months) compared with 21.4 months (15.8-27.1 months) in the "No PTR" group (p = 0.048). Subgroup analyses revealed a trend of improved survival with PTR in patients with stage IVA and IVB; however, the results were not statistically significant (p = 0.116 and 0.493, respectively). A subgroup analysis of PTR and RT combinations revealed no significant difference in median OS rates. CONCLUSION: For asymptomatic mCRC with synchronous unresectable distant metastasis, PTR following first-line therapy with bevacizumab plus FOLFIRI may provide a potential survival benefit, particularly in stage IVA/IVB patients compared with stage IVC patients. Additionally, RT for primary tumor did not provide an additional OS benefit in mCRC with unresectable metastasis. A prospective randomized trial with a larger sample size is essential to further elucidate the role of PTR in this context.

Outcomes of first-line treatment and their association with pretreatment neutrophil-to-lymphocyte ratio in patients with advanced renal cell carcinoma: Insights from a tertiary care institute in Pakistan.

Background: Renal cell carcinomas (RCCs) are renal parenchymal neoplasms that contribute to <5% of cancer cases worldwide. Within the diverse group of renal tumours, clear cell carcinoma is the most common subtype. The recommended first-line treatment for metastatic disease is a tyrosine kinase inhibitor given either as monotherapy or in combination with an immune checkpoint inhibitor, based on improved survival outcomes. These endpoints are not only influenced by the initial risk stratification but also by certain variables such as the neutrophil-to-lymphocyte (NLR) ratio. Methods: A retrospective review was conducted to evaluate the progression-free survival (PFS) with first-line treatment in patients with metastatic RCC treated at our institute from the year 2017-2021. We also investigated the association of PFS with both Memorial Sloan Kettering Cancer Center risk groups and the pretreatment NLR ratio. Results: Overall, 35 patients were enrolled after fulfilling the eligibility criteria. Of these, 25 patients received Pazopanib, 5 patients were treated with Sunitinib and the remaining patients were administered Pembrolizumab with Axitinib. Two-thirds of the study population belonged to the intermediate-risk group. The median PFS for all participants was 16 months. Among the overall population, patients in the favourable-risk group demonstrated superior PFS. Patients with elevated pretreatment NLR experienced shorter PFS compared to the patients with low to normal NLR. Conclusion: This review highlights the prognostic significance of initial risk stratification and pretreatment NLR in predicting the response to first-line treatment in metastatic RCC patients. As this is a comprehensive study emphasizing the outcomes of metastatic RCC in Pakistan, it fills a void in the literature by providing invaluable perspectives on the real-world outcomes of patients. This not only enhances our understanding of disease management in this region but also lays the foundation for future investigations.

First-line treatment of EGFR-mutated non-small cell lung cancer with brain metastases: a systematic review and meta-analysis.

This systematic review and network meta-analysis evaluates first-line treatment options for patients with EGFR-mutant non-small cell lung cancer (NSCLC) and brain metastases. We analyzed 24 randomized controlled trials (RCTs) involving 2,682 patients, comparing various EGFR tyrosine kinase inhibitors (TKIs) and combination therapies. Direct comparisons showed that the addition of bevacizumab or chemotherapy to first-generation (1G) EGFR-TKIs improved overall survival (OS) compared to 1G TKIs alone, with HRs of 0.704 (95% CI: 0.433-0.973) and 0.682 (95% CI: 0.464-0.899), respectively. However, third-generation (3G) TKI monotherapy did not significantly improve OS compared with 1G TKIs, with an HR of 0.855 (95% CI: 0.511-1.198). Indirect comparisons suggested that the combination of 3G TKIs with chemotherapy provided the most significant improvements in OS and progression-free survival (PFS), significantly outperforming 3G TKIs, with HRs of OS 1.69 (95% CI: 1.14-3.4) and PFS 2.13 (95% CI: 1.28-3.54). Intracranial PFS was best with 1G TKIs plus bevacizumab. Our findings suggest that 3G EGFR-TKIs in combination with chemotherapy may be the most effective strategy for patients with EGFR-mutant NSCLC and brain metastases, though further head-to-head trials are needed for validation.

First-Line Therapy in Metastatic, RAS Wild-Type, Left-Sided Colorectal Cancer: Should Everyone Receive Anti-EGFR Therapy?

PURPOSE OF REVIEW: This narrative review explores the efficacy and applicability of anti-EGFR therapy as the first-line treatment for patients with RAS wild-type (WT) left-sided metastatic colorectal cancer (mCRC). It critically examines current guidelines, along with recent evidence in the literature, to assess whether it should be universally applied. RECENT FINDINGS: Recent evidences highlight the variability of the response to anti-EGFR therapies due to molecular diversity and several clinical factors, such as RAS mutational status and primary tumor location. Anti-EGFR plus chemotherapy is the standard first-line treatment for most patients with MSS, RAS-WT, left-sided mCRC. Whether this combination is the best treatment for these patients remains an open question. This review delves into the role of EGFR inhibition in mCRC, focusing on clinical factors and the knowledge of biology, molecular targets, and biomarkers. It underscores the crucial role of a personalized approach, empowering healthcare providers and equipping them with the confidence to make informed decisions.

Tislelizumab plus chemotherapy as first-line treatment of locally advanced or metastatic nonsquamous non-small-cell lung cancer (final analysis of RATIONALE-304: a randomized phase III trial).

BACKGROUND: The purpose of this study was to report an updated, final analysis with longer follow-up for the open-label phase III RATIONALE-304 study of first-line tislelizumab plus chemotherapy versus chemotherapy alone for advanced nonsquamous non-small-cell lung cancer (nsq-NSCLC). MATERIALS AND METHODS: Patients with histologically confirmed stage IIIB/IV nsq-NSCLC were randomized (2 : 1) to 4-6 cycles of tislelizumab plus platinum-based chemotherapy and pemetrexed every 3 weeks, followed by maintenance tislelizumab and pemetrexed, or platinum-based chemotherapy and pemetrexed alone every 3 weeks followed by maintenance pemetrexed. The primary endpoint was independent review committee (IRC)-assessed progression-free survival (PFSIRC). Overall survival (OS), safety, and tolerability were secondary endpoints. RESULTS: Overall, 334 patients were randomized (tislelizumab plus chemotherapy: n = 223; chemotherapy: n = 111). At final analysis (median follow-up 16.1 months), safety/tolerability profiles in both arms were consistent with the interim analysis. Tislelizumab plus chemotherapy continued to demonstrate prolongation of PFSIRC versus chemotherapy alone {stratified hazard ratio (HR) 0.63 [95% confidence interval (CI) 0.47-0.86]; median PFSIRC 9.8 months (95% CI 8.9-11.7 months) versus 7.6 months (95% CI 5.6-8.0 months), respectively}. OS stratified HR for tislelizumab plus chemotherapy versus chemotherapy was 0.90 (95% CI 0.63-1.28), with median OS of 21.4 months (95% CI 17.7 months-not estimable) versus 21.3 months (95% CI 15.6 months-not estimable), respectively. At a subsequent ad hoc analysis (median follow-up 19.3 months), OS HR between arms was 0.85 (95% CI 0.63-1.14); when adjusted for crossover using the two-stage method, the OS HR was 0.68 (95% CI 0.48-0.96). CONCLUSIONS: After longer follow-up, first-line tislelizumab plus chemotherapy continued to demonstrate a manageable safety profile and a favorable PFS benefit over chemotherapy alone in patients with advanced/metastatic nsq-NSCLC.

A phase 2 trial of gemcitabine plus toripalimab for cisplatin-ineligible patients with recurrent or metastatic nasopharyngeal carcinoma.

Cisplatin is a cornerstone chemotherapy for nasopharyngeal carcinoma (NPC); however, certain patients are ineligible for cisplatin-based regimens. This phase 2 trial (NCT04405622) evaluated the efficacy and safety of gemcitabine and toripalimab in previously untreated patients with recurrent or metastatic NPC who were either ineligible for cisplatin or had experienced severe adverse events from prior cisplatin-based treatments. Patients received gemcitabine (1,000 mg/m2) and toripalimab (240 mg) every three weeks for six cycles, followed by toripalimab monotherapy for up to two years. The primary endpoint was the incidence of grade ≥3 adverse events, while secondary endpoints included objective response rate (ORR) and overall survival (OS). Of 30 screened patients, 21 were enrolled. No treatment-related fatalities occurred, with the most frequent adverse events being headache and nausea. The ORR was 61.9%, coupled with a disease control rate of 100%. Overall, gemcitabine plus toripalimab demonstrated low toxicity and promising efficacy for this specific patient cohort.

Efficacy and Safety of Pembrolizumab plus Axitinib combination for Metastatic Renal Cell Carcinoma in a Real-World Scenario: Data From the Prospective ProPAXI Study.

BACKGROUND: Pembrolizumab/Axitinib combination is approved as first-line therapy in mRCC. The aim of this study is to evaluate outcomes of PAXI combo in the real-world in Italy. METHODS: This is a prospective study including patients diagnosed with mRCC who received combination as first-line therapy in recruiting Italian Centers. Data about patient characteristics, safety and outcome were collected. RESULTS: 170 pts have been treated from December 2020 to September 2023. The majority had clear-cell histology (83%). Sarcomatoid feature was present in 33%of available cases. About one half of patients (55%) had synchronous metastasis. In 58% of cases nephrectomy was performed, of which 27% were cytoreductive and 4% were deferred nephrectomies. Lung metastases were identified in 106 patients (62%), bone and liver involvement in 66 and 29 patients (38.8% and 17.1%) respectively. Stratifying by IMDC criteria, 32 patients (18.8%) were at favorable-risk, 106 (62.4%) at intermediate-risk, and 32 (18.8%) at poor-risk. At time of analysis, treatment was ongoing in 49% of patients. Progression occurred in 45% of patients. Median PFS was 19.2 months (95% CI: 15-NR). With a median follow-up of 19.3 months (range 1.3-34.5), at 24-months and 36-months landmark analysis 62% (95% CI, 53-70) and 58% (95% CI, 47-69) of treated patients are still alive respectively. Disease control rate was achieved in 84.6% of patients: 4.3% reached a complete response, 52% had a partial response and 28.8% a stable disease. Primary progression was observed in 15.3% of patients. In the multivariate analysis, the prognostic significance of age ≥ 65 years, non-clear cell histology, IMDC score, and adverse events and gender interaction as predictors of worse OS were confirmed. CONCLUSION: This is the first available prospective study on first-line Pembrolizumab/Axitinib combination in real world scenario. Our findings support the effectiveness and safety of first-line this combination in mRCC and reveal that gender emerged as a prognostic factor in relation to the occurrence of adverse events.

Survival analysis of the metastatic cohort of Italian Association of Medical Oncology (AIOM) GARIBALDI survey.

This analysis from the GARIBALDI study was aimed to address the role of center self-declared expertise, type and commitment on the overall survival (OS) of patients with metastatic Pancreatic Ductal Adenocarcinoma (mPDAC). Treatment-naïve patients ≥18-year with pathological diagnosis of mPDAC were enrolled. OS was defined as the time from chemotherapy start to death from any cause. The impact of clinical-demographic and centers characteristics on OS was evaluated using Cox models. Between July 2017 and October 2019, 473 patients enrolled in 43 centers were eligible for this analysis. Median age was 69.3 (first-third quartile 61.2-74.5); 46.1 % females; 90.8 % ECOG PS 0-1; 67.4 % had liver metastases; median CA19.9700.5 UI/mL (first-third quartile 77.5-6629.5). For 37.1 % of patients chemotherapy started <4 weeks from diagnosis; 69.9 % of patients received nab-paclitaxel + gemcitabine; 16.9 % gemcitabine alone; 7.6 % FOLFIRINOX. The median follow-up was 51.8 months and 428 patients died. No statistically significant role of the type of institution was observed. Additionally, no statistically significant role of neither the self-declared expertise nor the accrual rate was observed. The GARIBALDI study suggests that the self-declared center expertise and the academic brand are not associated to OS in patients with mPDAC, while center commitment warrants further exploration.

Phase Ib study of anti-PD-L1 monoclonal antibody socazolimab in combination with nab-paclitaxel as first-line therapy for advanced urothelial carcinoma.

BACKGROUND: PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have demonstrated activity in the post-platinum and platinum-ineligible settings for advanced urothelial carcinoma (aUC). As only around 50% of patients with aUC can tolerate platinum-containing treatment, treatments combining first-line ICIs with non-platinum drugs are urgently needed. Therefore, we assessed the safety and efficacy of the anti-PD-L1 monoclonal antibody Socazolimab in combination with nab-paclitaxel as first-line therapy in aUC (NCT04603846). METHODS: This was a multi-center, single-arm, phase Ib study that enrolled patients with treatment-naive aUC. Patients received Socazolimab (5 mg/kg) and nab-paclitaxel (260 mg/m2) Q3w. The primary endpoint was safety and tolerability of the combination regimen. Second endpoints were the objective response rate (ORR) and progression-free survival. RESULTS: Between September, 2020 and September, 2021, 20 patients with urothelial carcinoma were enrolled, arising from renal pelvis (5), bladder (8), and ureter (7). After a median follow-up of 17 months, the median number of treatment cycles was 12. No patients had dose limiting toxicity. All patients had treatment-related adverse events (TRAEs), most of which were grade 1 or 2. The common TRAEs (≥20%) were peripheral neurotoxicity, alopecia, rash, increased ALT, weight loss, weakness, pruritus, increased AST, increased γGT, increased ALP, neutropenia, emesis, and anorexia. Nine patients (45%) developed grade 3 TRAEs including peripheral neurotoxicity (30.0%), increased ALT (10.0%), and increased γGT (5.0%). Two patients (10%) discontinued treatment because of grade 3 mouth ulcer (n = 1) and grade 2 lung fibrosis (n = 1). No grade 4-5 TRAEs were observed. Among the 17 patients who had received at least one tumor assessment, ORR was 58.8% (95% CI, 32.9%-81.6%) and the median progression-free survival was 8.3 months (95% CI, 5.2-19.5). The median duration of response was 13.3 months (95% CI, 2.0-20.1), and the overall survival was 19.5 months (95% CI, 11.2-not reached). CONCLUSION: Socazolimab combined with nab-paclitaxel has shown good safety and promising antitumor activity as first-line therapy in patients with advanced urothelial carcinoma.

Enfortumab vedotin plus pembrolizumab as a first-line treatment for advanced urothelial carcinoma: a cost-effectiveness analysis from China based on the EV-302 trial.

Background: The efficacy and safety of enfortumab vedotin combined with pembrolizumab (EV-PEMB) was investigated as a first-line treatment for advanced urothelial carcinoma (UC) in a phase III clinical trial (EV-302). The trial findings indicated significant prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy with a favorable safety profile. However, EV-PEMB is costly and it is unknown whether it is cost-effective compared to chemotherapy. This study aimed to conduct a cost-effectiveness analysis of EV-PEMB versus chemotherapy as a first-line treatment for advanced UC from the perspective of the Chinese healthcare system. Methods: A Markov model with three distinct health states was developed to assess the cost-effectiveness of EV-PEMB as a first-line treatment for advanced UC versus chemotherapy based on the EV-302 trial. Drug costs were obtained from national tender prices. Other expenses and utility values were sourced from the literature or expert advice. The findings of the study included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). We conducted a one-way sensitivity analysis and probabilistic sensitivity analysis to ensure the model's robustness. Results: The EV-PEMB regimen demonstrated a gain of 3.22 QALYs at $375,420.24, compared to the chemotherapy regimen with 1.70 QALYs at $23,369.67. ICER for EV-PEMB compared to chemotherapy was at $232,256.16 per QALY gained. In China, at a willingness-to-pay threshold of $38,133 per QALY, EV-PEMB has a 0% probability of being cost-effective as a first-line treatment for advanced UC compared to chemotherapy. Conclusion: From the perspective of the Chinese healthcare system, EV-PEMB is unlikely to be a cost-effective first-line treatment option for advanced UC compared to chemotherapy.

Dose-escalation of second-line and first-line asciminib in chronic myeloid leukemia in chronic phase: the ASC2ESCALATE Phase II trial.

Up to 40% of newly diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP) discontinue treatment by 5 years, primarily due to resistance or intolerance. Rates of resistance to second-line (2L) treatment are also high. Some patients with resistance respond with dose escalation of tyrosine kinase inhibitors (TKIs). Asciminib demonstrated safety and efficacy across a broad dosage range. ASC2ESCALATE is an ongoing, Phase II, multicenter, single-arm, dose-escalation study of asciminib in 2L and first-line treatment of CML-CP. The primary end point is major molecular response at 12 months in 2L. Secondary end points include molecular responses at and by scheduled time points, survival, and safety. ASC2ESCALATE is the first study investigating asciminib in CML-CP following failure of one prior TKI.Clinical Trial Registration: NCT05384587 (ClinicalTrials.gov).

ASC2ESCALATE is an ongoing, Phase II, multicenter, single-arm, #dose-escalation study of oral asciminib in first-line and second-line treatment for patients with #CML in chronic phase.

Efficacy and Tolerance of First-Line Afatinib in Elderly NSCLC Patients with EGFR Mutations in Vietnam: A Multicenter Real-World Study.

BACKGROUND: Afatinib, a second-generation epidermal growth factor receptor(EGFR) tyrosine kinase, has proven effective for non-small-cell lung cancer (NSCLC) patients with EGFR mutations through randomized controlled trials and real-world studies. Elderly patients exhibit unique characteristics in terms of physical condition and comorbidities, leading to differences in clinical practice for selecting the initial dosage and making dose adjustments compared to younger patients. This study aims to evaluate the effectiveness and adverse effects of first-line Afatinib treatment in elderly patients with NSCLC harboring EGFR mutations in Vietnam in a real-world context. METHODS: We conducted a retrospective analysis of 135 patients, aged 65 years and older, across nine cancer centers in Vietnam. These patients, who harbored drug-sensitive EGFR mutations (excluding de novo T790M), received first-line Afatinib treatment between April 2018 and June 2022. The primary endpoints, time to treatment failure (TTF), and overall survival (OS) were assessed using the Kaplan-Meier method, and comparisons were conducted using the log-rank test. Secondary endpoints included the overall response rate (ORR) according to RECIST 1.1 and adverse effects as classified by CTCAE 4.0. RESULTS: The median age was 71.2 years (SD ± 5.3). Comorbidities included cardiovascular disease (20.7%), diabetes (5.2%), chronic obstructive pulmonary disease (2.2%), and hepatitis B (0.7%). Common mutations constituted 71.9% of cases, with uncommon mutations representing 28.1%. Brain metastases were observed in 24.4% of patients. Initial treatment doses were 40 mg for 35.6% of patients and 30 mg for 62.2%. With a median follow-up of 34.3 months, the median TTF was 16.3 months (95% CI: 15.4-19.5), and the median OS was 32.9 months (95% CI: 28.9-37.5). Factors associated with decreased OS included poor performance status, current smoking, and the presence of uncommon mutations. The ORR was 77.8%, with a complete response of 11.1% and a disease control rate of 94.1%. The most common toxicities were dermatologic and mucosal, including diarrhea (55.6%), rash (48.9%), and stomatitis (40.7%), predominantly in grades 1 and 2. Initiating treatment at doses below 40 mg significantly reduced most toxicities compared to the 40 mg dose. The presence of brain metastases did not significantly affect ORR, TTF, or OS. Starting treatment at doses below 40 mg significantly lowered the response rate but did not impact TTF or OS. CONCLUSION: First-line treatment with Afatinib in elderly patients with NSCLC and EGFR mutations demonstrates significant efficacy and manageable toxicity in a Vietnamese multicenter real-life setting. The effectiveness of Afatinib was confirmed, with known and well-controlled adverse effects, supporting its use in this patient population.

Comparison of tucidinostat with CHOP-like versus CHOP-like in first-line treatment of peripheral T-cell lymphoma: a single-center real-world study.

Tucidinostat has been approved by the Chinese FDA for relapsed/refractory Peripheral T cell lymphoma (PTCL), but its efficacy in newly diagnosed PTCL has not been confirmed. In this study, we aimed to compare the efficacy of tucidinostat combined with CHOP-like (C + CHT) versus CHOP-like alone (CHT) in newly diagnosed PTCL patients. Of the PTCL patients, 109 were newly diagnosed. Patients in the C + CHT group who achieved objective response received tucidinostat maintenance therapy. A total of 36 pairs (n = 72) were matched at a ratio of 1:1 using propensity scoring. The matching criteria included: whether the Prognostic index for the peripheral T-cell lymphoma-not otherwise specified subtype (PIT) was ≥ 2, the pathological subtype, age > 60 years, and gender (matching tolerance = 0.024). A significantly higher objective response rate (ORR) (P = 0.016), 2-year progression-free survival (PFS) (P = 0.026), and 2-year survival rate (P = 0.017) was observed for the C + CHT group as compared to the CHT group. After propensity score matching (PSM), the C + CHT group as compared to the CHT group displayed significantly longer PFS (P = 0.035) and overall survival (OS) (P = 0.029). For the C + CHT group in the per-protocol set, the effect values showed a significant benefit in terms of both PFS (P = 0.027) and OS (P = 0.019). Common grade 3-4 haematological adverse events (AEs), had comparable incidence in each group; while common non-haematological AEs, including elevated AST and ALT were higher in the C + CHT group than in the CHT group. Our study suggests that the tucidinostat with CHOP-like regimen and sequential tucidinostat maintenance after objective remission provides a promising therapeutic approach for treating newly diagnosed PTCL patients.