Progression-free Survival Hazard Ratio Research Articles

Addition of Bevacizumab to Chemotherapy and Its Impact on Clinical Efficacy in Cervical Cancer: A Systematic Review and Meta-Analysis

Background and Objectives: Cervical cancer is the third leading cause of cancer-related mortality in females. One of the most successful therapeutic modalities to date is suppressing vascular endothelial growth factor (VEGF)-mediated angiogenesis. Bevacizumab is a monoclonal antibody that targets VEGF-A. The outcomes for cervical cancer patients treated with bevacizumab in combination with platinum-based chemotherapy have been explored in several studies. This study aimed to assess the impact of bevacizumab on progression-free survival (PFS) and overall survival (OS) in patients with metastatic cervical cancer. Materials and Methods: This systematic review was registered in PROSPERO (CRD42023456755). Following PRISMA guidelines, a comprehensive literature search on PubMed and Google Scholar identified 28 studies meeting the inclusion criteria. The outcomes of interest were PFS and OS. The statistical analysis computed hazard ratios (HRs) with 95% confidence intervals (CIs). The study also included a subgroup analysis by cervical cancer stage. Results: The pooled analysis revealed that bevacizumab-based therapy significantly improved both PFS with HR 0.77 (95% CI: 0.58–0.96; p < 0.01; I2 = 58%) and OS with HR 0.63 (95% CI: 0.45–0.89; p < 0.01; I2 = 41%) in cervical cancer patients. Subgroup analysis by stage of cervical cancer demonstrated better efficacy of bevacizumab in metastatic stage IVB cervical cancer patients indicated by HR for PFS (0.69, 95% CI: 0.54–0.79; p < 0.01) and HR for OS (0.57, 95% CI: 0.46–0.73; p < 0.01). Conclusions: Bevacizumab exhibits a significant increase in PFS and OS, underscoring the efficacy of anti-angiogenesis therapy in cervical cancer, particularly in stage IVB metastatic cervical cancer patients.

The load of hepatitis B virus reduces the immune checkpoint inhibitors efficiency in hepatocellular carcinoma patients

IntroductionChronic viral infection may lead to an immunosuppressive microenvironment, whereas the association between virus-related indicators and treatment response in hepatocellular carcinoma(HCC) patients undergoing immune checkpoint inhibitors(ICIs) therapy remains a topic of debate. We aim to investigate the influence of hepatitis virus on the ICI efficiency in HCC patients through a meta-analysis.MethodsWe searched PubMed, Cochrane Library, Embase, and Web of Science until 14 July 2024 to identify cohort studies involving ICIs treatments in HCC patients. We extracted data from the literature related to hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, baseline HBV load, and antiviral therapy. Overall survival (OS) and progression-free survival (PFS) were considered as the primary endpoints, while objective response rate (ORR) was regarded as a secondary endpoint.ResultsWe included 55 cohort studies published between 2019 and 2024, involving a patient population of 7180 individuals. Summarized hazard ratio (HR) comparing HBV infection with non-HBV infection in the context of ICIs therapy revealed no significant association between HBV infection and either mortality risk or progression risk with the pooled HR for OS of 1.04(95%CI: 0.93-1.16, P=0.483) and the pooled HR for PFS of 1.07(95%CI:0.96-1.20, P=0.342). HBV infected patients with HCC may have better tumor response than non-HBV infected patients receiving ICIs with the combined relative risk(RR) for ORR was 1.94 (95%CI: 1.12-3.38, P=0.002). High baseline HBV load is associated with poor survival outcomes in patients with HCC who receive ICIs with the pooled HR for OS was 1.74 (95%CI: 1.27-2.37, P=0.001), thereby antiviral therapy has the potential to significantly enhance prognostic outcomes with the pooled HR for OS was 0.24 (95% CI: 0.14-0.42 P<0.001) and the pooled HR for PFS was 0.54 (95% CI: 0.33-0.89 P=0.014).ConclusionIn individuals with HCC who received ICIs, there was no notable link found between HBV or HCV infection and prognosis. However, HBV infection showed a connection with improved tumor response. A higher initial HBV load is linked to worse survival results in HCC patients undergoing ICIs treatment and antiviral therapy can significantly improve its prognosis.

The prognostic value of pretreatment [18F]FDG PET/CT parameters in esophageal cancer: a meta-analysis.

This study aims to evaluate the prognostic implications of pretreatment [18F]FDG-PET metrics in esophageal cancer patients through a meta-analysis of the existing literature. We carefully searched electronic databases, including PubMed and Embase, from inception to April 1, 2024, to identify studies describing the prognostic value of pretreatment PET metrics for advanced esophageal cancer. Clinical endpoints examined were overall survival (OS), recurrence-free survival (RFS)/disease-free survival (DFS), and progression-free survival (PFS). Hazard ratios (HRs) for PFS and OS were taken directly from the original reports. Forty-seven publications, including 5504 patients, were included in our analysis. OS and PFS were analyzed in 31 and nine studies, respectively, and DFS/RFS was analyzed in 16 studies. The comprehensive pooled analysis revealed significant associations between metabolic parameters derived from positron emission tomography (PET) imaging and clinical outcomes. Expressly, the pooled HR indicated that patients with higher SUVmax were significantly associated with poor PFS (HR: 1.06; 95% CI: 1.01-1.12, p = 0.011) and poor RFS/DFS (HR: 1.09; 95% CI: 1.02-1.18, p = 0.019). Patients with higher SUVmean were significantly associated with poorer OS (HR: 1.07; 95% CI: 1.01-1.14, p = 0.025). High MTV was significantly associated with inferior OS (HR: 1.02; 95% CI: 1.00-1.05, p = 0.049). High TLG was significantly associated with poorer RFS/DFS (HR: 2.02; 95% CI: 1.11-3.68, p = 0.022). This study unveiled pretreatment FDG-derived parameters as valuable prognostic indicators in assessing esophageal cancer outcomes. Specifically, SUVmax is associated with PFS and RFS/DFS. SUVmean and MTV were correlated with OS, and TLG was only associated with RFS/DFS. Question Inconsistent findings on the prognostic value of pretreatment [18F]FDG PET parameters in esophageal cancer require comprehensive analysis to clarify their role in outcome prediction. Findings Higher pretreatment [18F]FDG-PET metrics (SUVmax, SUVmean, MTV, TLG) are associated with poor survival outcomes, emphasizing their potential value in enhancing prognostic assessments for esophageal cancer. Clinical relevance This study highlights the prognostic significance of pretreatment [18F]FDG-PET metrics in esophageal cancer, providing valuable insights for patient outcome prediction and potentially guiding personalized treatment strategies.

Serum Alpha-fetoprotein Associated with Treatment Efficacy of Immune Checkpoint Inhibitors in Patients with Hepatocellular Carcinoma: A Meta-Analysis and a Retrospective Cohort Study

Context: Serum alpha-fetoprotein (AFP) has been shown to be valuable in tumor staging and predicting survival outcomes. In this investigation, we conducted a retrospective cohort analysis and a meta-analysis to assess the predictive significance of initial AFP levels in patients with hepatocellular carcinoma (HCC) who underwent treatment with immune checkpoint inhibitors (ICIs). Methods: We searched databases from inception until 14 July 2024 to identify cohort studies involving ICI treatments in HCC patients with baseline AFP data. We also retrospectively analyzed patients with HCC treated with ICIs to assess the therapeutic effect in the high AFP (AFP ≥ 400 ng/mL) group and the low AFP (AFP < 400 ng/mL) group in terms of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: In the meta-analysis, a total of 34 studies, comprising 8,799 patients, were included, while the retrospective cohort study encompassed 55 patients. In the meta-analysis, the summarized hazard ratios (HRs) of AFP ≥ 400 ng/mL versus AFP < 400 ng/mL for ICI therapy indicated that the high AFP group had a poorer outcome compared to the low AFP group, with a pooled HR for OS of 1.69 (95% CI: 1.57 - 1.82, P < 0.001) and a pooled HR for PFS of 1.47 (95% CI: 1.33 - 1.63, P < 0.001). In the retrospective cohort study, higher AFP levels were associated with a lower DCR for ICIs, with a DCR of 42.9% in the high AFP group and 77.8% in the low AFP group (P = 0.008). Cox model analysis showed that higher serum AFP was an independent predictor for shorter OS (HR 3.584, 95% CI: 1.466 - 8.762, P = 0.005). The toxicity analysis also displayed a strong association between high AFP and the occurrence of immune-related adverse events (irAEs) (P = 0.008). Conclusions: Higher serum AFP is associated with poorer efficacy of ICI treatment in HCC patients.

Gut microbiota diversity is prognostic and associated withbenefit from chemo-immunotherapy in metastatic triple-negative breast cancer.

The gut microbiota influences multiple aspects of human health and disease. Several studies have indicated an association between the gut microbiota and response to immune checkpoint inhibitors in various cancers, but there is scarce data from breast cancer. The randomized ALICE trial demonstrated improved progression-free survival (PFS) from adding the programmed cell death 1 ligand 1 (PD-L1) inhibitor atezolizumab (atezo) to immunomodulating chemotherapy (chemo) in metastatic triple-negative breast cancer (mTNBC), even for PD-L1negative disease. Herein, we investigated the microbiota composition and dynamics in the ALICE patients and their association with clinical outcome, by analyzing fecal samples collected at baseline and after 8 weeks. We applied 16S (V3-V4) rRNA sequencing to characterize the diversity and taxonomic composition. Kaplan-Meier and Cox proportional hazard models were used for time-to-event analyses. We found that high alpha diversity by Faith's phylogenetic diversity (PD) at baseline was associated with prolonged PFS in the total study population and in the atezo-chemo arm, but not in the placebo-chemo arm. Moreover, Faith's PD appeared to be predictive of benefit from atezolizumab. Patients with high Faith's PD exhibited a PFS hazard ratio of 0.34 (P = 0.018) in favor of the atezo-chemo arm, compared to 0.83 (P = 0.62) in the low Faith's PD group. Faith's PD was significantly reduced during treatment. At baseline, Bifidobacterium was significantly overrepresented in patients without clinical benefit in the atezo-chemo arm, but not in the placebo-chemo arm. These findings suggest that alpha diversity by Faith's PD should be further investigated as a prognostic and predictive biomarker in patients with mTNBC receiving chemo-immunotherapy.

Immunotherapy benefits for large brain metastases in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) patients with large brain metastases (BrM) defined as >2cm in diameter historically face grim prognoses. With immunotherapy emerging as a promising avenue for BrM management and being commonly used in NSCLC, its application in addressing large BrM remains underexplored. This retrospective study conducted across the MedStar Georgetown Cancer Network aimed to assess the efficacy of immunotherapy in non-biomarker driven NSCLC patients with large BrM following initial treatment. Thirty-six patients were included, all of whom underwent neurosurgery and/or radiation before commencing immunotherapy. The median intracranial progression-free survival (PFS) was 9.2 months and the median overall survival (OS) reached 31 months. Utilizing multivariable Cox penalized regression, the intracranial PFS hazard ratio (HR) was 0.07 (95% confidence interval (CI), 0.02-0.26) for patients who received at least 90 days of immunotherapy compared to those who did not. Each additional 30 days of immunotherapy was associated with an OS HR 0.77 (95% CI, 0.67-0.90). This real-world data highlights the potential of immunotherapy in large BrM NSCLC patients, a population often excluded from clinical trials. This study contributes insights that can inform future treatment approaches, emphasizing the need for further exploration of immunotherapy's role in enhancing outcomes for this challenging patient population.

Comparative analysis of efficacy and safety of combined immunotherapy and immune targeted therapy in the first-line treatment of advanced renal cell carcinoma: a real-world study

Aim. To compare of efficacy and safety of combined immune therapy (dual immune-oncology – IO combination therapies, IO-IO) and immune targeted therapy (ITT) in the first line treatment of patients with advanced renal cell carcinoma (RCC) treated in real world clinical practice. Materials and methods. The ambispective study enrolled patients with metastatic RCC aged ≥18 years, with measurable neoplastic lesions, who were treated with first-line IO-IO therapy or ITT. The primary endpoint was progression-free survival (PFS). Results. The study included data from 126 patients treated with IO-IO [46 (36.5%) patients of the IMDC intermediate and poor prognostic groups] or ITT [80 (63.5%) patients of all IMDC prognostic groups]. In a median follow-up of all patients of 16.1 (0.1–44.9) months, the median PFS was 16.1 (10.9–21.3) months, the median overall survival (OS) was not reached; one-year OS was 83.0%; the objective response rate on the first line of therapy was 44.4% with a complete response rate of 3.2%. The rate of tumor control was 88.1%. In the overall population, ITT versus IO-IO provided a significant benefit in terms of ORR (51.2% vs 32.6%; p=0.032), PFS (median 22.9 months vs 8.0 months; p=0.004) and one-year OS (87.5% vs 65.2%; p=0.042). In the IPTW population, multivariate analysis confirmed the independent prognostic significance of the treatment regimen for PFS (hazard ratio, 2.3; 95% confidence interval, 1.1–4.8; p=0.037) and OS (hazard ratio, 2.3; 95% confidence interval 1.1–4.8; p=0.037). No difference in the safety profile of IO-IO and ITT was identified. Conclusion. The results support the hypothesis that ITT is more effective than IO-IO in the first-line treatment of advanced RCC in patients of IMDC intermediate and poor prognostic groups.

Delayed Separation of Kaplan-Meier Curves is Commonly Observed in Studies of Advanced/Metastatic Solid Tumors Treated with Anti-PD-(L)1 Therapy: Systematic Review and Meta-Analysis.

Immune checkpoint inhibitor (ICI) Kaplan-Meier (KM) curves often show delayed survival benefit followed by long-term survival in a subgroup of patients. Such outcomes can violate the proportional hazards assumption, leading to a loss of statistical power. We aimed to determine common trends in delayed separation to inform future ICI clinical trials. A literature search was performed using Trialtrove® to identify phase III trials of antiprogrammed cell death (ligand)-1 (anti-PD-[L]1) agents in locally advanced/metastatic solid tumors published between January 2010 and September 2021. The frequency of delayed separation of overall survival (OS) and progression-free survival (PFS) KM curves, correlation between duration of delayed separation in OS/PFS KM curves, and correlation between duration of delayed separation in OS/PFS KM curves with corresponding hazard ratios (HRs) were assessed in all-comer and PD-L1 enriched populations. Eighty-five studies with OS/PFS KM curves were identified. Most studies showed delayed separation of OS (> 67.9%) and PFS (> 54.5%) KM curves. The correlation between the duration of delayed separation in OS/PFS KM curves was strongest in the PD-L1 enriched population (adjusted R2 = 0.66). No correlation was seen between the duration of delayed separation of OS KM curves and OS HR. A modest correlation was seen between the duration of delayed separation of PFS KM curves and PFS HR in all-comer and PD-L1 enriched populations (adjusted R2 = 0.24 and 0.31, respectively). Delayed separation of KM curves was common in clinical trials of anti-PD-(L)1 agents. Understanding delayed separation is key to clinical study designs and assessing outcomes with ICIs.

Radiomic Features as Artificial Intelligence Prognostic Models in Glioblastoma: A Systematic Review and Meta-Analysis.

Glioblastoma, the predominant primary tumor among all central nervous systems, accounts for around 80% of cases. Prognosis in neuro-oncology involves assessing the disease's progression in different individuals, considering the time between the initial pathological diagnosis and the time until the disease worsens. A noninvasive therapeutic approach called radiomic features (RFs), which involves the application of artificial intelligence in MRI, has been developed to address this issue. This study aims to systematically gather evidence and evaluate the prognosis significance of radiomics in glioblastoma using RFs. We conducted an extensive search across the PubMed, ScienceDirect, EMBASE, Web of Science, and Cochrane databases to identify relevant original studies examining the use of RFs to evaluate the prognosis of patients with glioblastoma. This thorough search was completed on 25 July 2024. Our search terms included glioblastoma, MRI, magnetic resonance imaging, radiomics, and survival or prognosis. We included only English-language studies involving human subjects, excluding case reports, case series, and review studies. The studies were classified into two quality categories: those rated 4-6 were considered moderate-, whereas those rated 7-9 were high-quality using the Newcastle-Ottawa Scale (NOS). Hazard ratios (HRs) and their 95% confidence intervals (CIs) for OS and PFS were combined using random effects models. In total, 253 studies were found in the initial search across the five databases. After screening the articles, 40 were excluded due to not meeting the eligibility criteria, and we included only 14 studies. All twelve OS and eight PFS trials were considered, involving 1.639 and 747 patients, respectively. The random effects model was used to calculate the pooled HRs for OS and PFS. The HR for OS was 3.59 (95% confidence interval [CI], 1.80-7.17), while the HR for PFS was 4.20 (95% CI, 1.02-17.32). An RF-AI-based approach offers prognostic significance for OS and PFS in patients with glioblastoma.

Blinded independent central review versus local investigator assessment of PFS in RCTs of immunotherapy in advanced cancers: A systematic review and meta-analysis

BackgroundAssessment of Progression-free survival (PFS) events by investigators might be inaccurate in randomized controlled trials (RCTs) with open-label design. We explored differences in PFS evaluated by blinded independent central review (BICR) or local investigator assessment (IA) in trials testing immunotherapy (IO) in advanced cancers. MethodsWe systematically reviewed articles of RCTs investigating IO in advanced tumors, published in PubMed-indexed journals up to December 2023. For each RCT, we collected PFS results by BICR and by local IA. We calculated the discrepancy index (DI) as the ratio of BICR and IA Hazard Ratios (HRBICR/HRIA) for PFS. An overall DI and relative confidence interval (CI) were calculated using a fixed-effect model weighted for the inverse of variance. FindingsOnly 32/140 (22.9 %) RCTs reported both BICR and local IA PFS data, including 17,054 patients. PFS was the sole primary endpoint in 19/32 (59.4 %) and a co-primary endpoint 9/32 (28.2 %) trials. The study design was open label or double-blind in 17/32 (53.1 %) and 15/32 (46.9 %) RCTs, respectively. The overall DI was 1.07 (95 % CI 1.01–1.13; I2 =0, p = 0.02), revealing a more optimistic analysis of results in favor of local IA. In the 17 open-label trials, the overall DI was 1.09 (95 % CI 1.02–1.17, I2 =0, p = 0.02), revealing a more favorable interpretation of PFS results by local investigators. InterpretationWe found a statistically significant difference between BICR and local IA of PFS in trials of IO in cancer. These results suggest that the double assessment is recommended in RCTs testing IO, especially in open-label trials. FundingThis work was supported by the MFAG27826–2022 grant (Dr. Alberto Servetto).

Impact of systemic steroids on the efficacy of first line imatinib treatment of patients with advanced gastrointestinal stromal tumors (GISTs).

Effective management of adverse events is required to maintain sufficient imatinib dosing when treating patients with gastrointestinal stromal tumors (GISTs). Skin rash is a common adverse event of imatinib, which can be effectively controlled by systemic steroid treatment without imatinib dose modification or interruption. However, the impact of the use of systemic steroids on the efficacy of imatinib treatment remains unclear. Between October 2014 and February 2022, 277 consecutive patients from a prospective registry of GIST patients were included as the study population. Patients who started systemic steroids due to grade ≥ 3 skin rash or grade 2 skin rash with grade 2 pruritis were classified as the steroid group, whereas patients who did not develop a skin rash or those who did not require steroids for a mild skin rash were classified as the control group. Efficacy outcomes were compared between the two groups. Among the 277 patients, 30 (10.8%) were treated with systemic steroids for skin rash. There was no significant difference in progression free survival (PFS) or overall survival (OS) between the steroid and control groups (3-year PFS, 67.7% vs. 65.1%, p = 0.53; 3-year OS, 91% vs. 89.9%, p = 0.67, respectively). The use of systemic steroids was not an independent factor associated with PFS (hazard ratio 0.73, 95% confidence interval 0.36-1.49, p = 0.39) and OS (hazard ratio 0.37, 95% confidence interval 0.12-1.18, p = 0.09). In the steroid group, patients who successfully maintained the imatinib dosage showed a trend toward more favorable survival outcomes than those who did not (3-year PFS, 73.3% vs. 44.4%, p = 0.34; 3-year OS, 95.8% vs. 75.0%, p = 0.15, respectively). The use of systemic steroids for the control of imatinib induced severe skin rash did not adversely affect the efficacy outcomes of imatinib in patients with advanced GIST.

Cediranib and Olaparib Combination Compared With Cediranib or Olaparib Alone, or Chemotherapy in Platinum-Resistant or Primary Platinum-Refractory Ovarian Cancer: NRG-GY005.

We assessed the efficacy of cediranib, olaparib, and cediranib/olaparib compared with standard-of-care chemotherapy (SOC) in platinum-resistant or platinum-refractory epithelial ovarian cancer (PROC). NRG-GY005 is an open-label, four-arm, phase II/III superiority trial enrolling patients with high-grade serous/endometrioid PROC and one to three previous therapies. Key exclusion criteria included previous receipt of poly(ADP-ribose) polymerase inhibitor or receipt of antiangiogenic therapy in the recurrent setting. Treatment arms (SOC [once weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin], cediranib, olaparib, or cediranib/olaparib) were equally randomized. A preplanned interim futility analysis on the basis of progression-free survival (PFS) selected treatment arms to advance to phase III. PFS and overall survival (OS) were phase III coprimary end points, with hierarchical testing of PFS followed by OS to preserve type 1 error control, designed to have 90% power for a 0.625 PFS hazard ratio (HR). OS was tested after PFS in the multiple hierarchical testing procedure. Secondary end points included objective response rate (ORR) and patient-reported outcomes. Five hundred sixty-two eligible patients were enrolled for phase II/III. Three arms met PFS criteria to carry forward to phase III (SOC, cediranib/olaparib, and cediranib). Median PFS was 3.4, 5.2, and 4 months with SOC, cediranib/olaparib, and cediranib, respectively, with a median follow-up duration of 42.2 months. PFS HR estimates for cediranib/olaparib and cediranib (v SOC) were 0.796 (98.3% CI, 0.597 to 1.060) and 0.972 (98.3% CI, 0.726 to 1.300), respectively. Median OS was 13.6, 12.8, and 10.5 months, and of 443 patients with measurable disease, ORR was 8.6%, 24.7%, and 13.1% for SOC, cediranib/olaparib, and cediranib, respectively. No new safety signals were identified. In patients receiving cediranib/olaparib, no statistically significant difference was observed on the NFOSI-DRS-P subscale compared with SOC (98.3% CI, -1.3 to 1.5, P = .8725). The cediranib-containing arms demonstrated clinical activity on the basis of PFS but were not superior compared with SOC.

Pembrolizumab plus chemotherapy for advanced and recurrent cervical cancer: final analysis according to bevacizumab use in the randomized KEYNOTE-826 study

In KEYNOTE-826 (NCT03635567), pembrolizumab plus chemotherapy (± bevacizumab) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with persistent, recurrent, or metastatic cervical cancer. This exploratory analysis examined outcomes in patient subgroups defined by bevacizumab use. Eligible adult patients had persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix not previously treated with chemotherapy and not amenable to curative treatment; measurable disease per RECIST v1.1; and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1:1 to pembrolizumab 200 mg every 3 weeks or placebo for up to 35 cycles plus chemotherapy (± bevacizumab 15 mg/kg). Dual primary endpoints were OS and PFS per RECIST v1.1 by investigator assessment. Outcomes were assessed in subgroups defined by bevacizumab use. Hazard ratios (HRs) and 95% CIs were based on a stratified Cox regression model. 617 patients were randomized (pembrolizumab arm, n=308 [63.6% with bevacizumab]; placebo arm, n=309 [62.5% with bevacizumab]). The most common reason for bevacizumab exclusion was medical contraindication (75.9%). Among patients who received bevacizumab, HRs (95% CIs) for PFS favored the pembrolizumab arm in the PD-L1 combined positive score (CPS) ≥1 (0.56 [0.43-0.73]) and all-comer (0.57 [0.45-0.73]) populations; OS results were 0.60 (0.45-0.79) and 0.61 (0.47-0.80), respectively. Among patients who did not receive bevacizumab, HRs (95% CIs) for PFS also favored the pembrolizumab arm in the PD-L1 CPS≥1 (0.61 [0.44-0.85]) and all-comer (0.69 [0.50-0.94]) populations; OS results were 0.61 (0.44-0.85) and 0.67 (0.49-0.91), respectively. Among patients who received bevacizumab, grade ≥3 treatment-related adverse events occurred in 74.0% of patients in the pembrolizumab arm and 66.8% in the placebo arm. Pembrolizumab plus chemotherapy prolonged PFS and OS and had manageable safety compared with placebo plus chemotherapy in patient subgroups defined by bevacizumab use.

Analysis of progression-free and overall survival in ovarian cancer: Bevacizumab treatment outcomes using historical cohort.

Background: The incorporation of bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), has redefined therapeutic strategies for advanced ovarian cancer. This study evaluates the efficacy of bevacizumab combined with standard chemotherapy by comparing progression-free survival (PFS) and overall survival (OS) outcomes with a historical cohort of patients treated with standard chemotherapy alone. Methods: We conducted an analysis of 71 patients with advanced epithelial ovarian cancer treated at the University Clinical Center in Niš, Serbia, from April 2017 to March 2023. All patients received standard chemotherapy paired with bevacizumab and were monitored for progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier estimates. Subgroup analyses were performed based on age, ECOG performance status, presence of metastases, and pleural effusion. Additionally, a historical cohort of 30 patients treated with standard chemotherapy alone was used for comparison, and Cox regression analysis was conducted to identify factors influencing treatment outcomes. Results: The study findings indicate significant improvements in median PFS (20 months vs. 15 months) and OS (58 months vs. an undetermined upper limit) compared to the historical cohort. Subgroup analysis of the bevacizumab-treated group revealed that younger patients (<65 years) and those without metastases or pleural effusion exhibited notably better survival outcomes. The hazard ratio for PFS in patients younger than 65 was 0.65 (95% CI: 0.45-0.93), suggesting a substantial reduction in disease progression risk compared to older patients. Conclusion: Bevacizumab, when used alongside standard chemotherapy, significantly extends both PFS and OS in patients with advanced ovarian cancer. These benefits are particularly pronounced in younger patients. The results underscore the necessity of integrating bevacizumab into the treatment regimen for advanced ovarian cancer, advocating for tailored therapeutic strategies based on individual risk profiles and clinical characteristics. This study reinforces the pivotal role of bevacizumab in enhancing the current ovarian cancer treatment landscape and highlights the potential for further personalizing oncological care.

Optimising outcomes for frail patients with oesophagogastric (OG) cancers: The impact of dose reduction and comprehensive geriatric assessment.

303 Background: Delivery of appropriate management of elderly patients with OG malignancies in the palliative setting remains challenging and unpredictable. Incidence of OG cancers increases markedly with age, and there are growing numbers of elderly, frail and medically complex patients referred to oncology services for treatment. An adaptive approach to their management is required, tailored to their complex medical needs. The GO2 study sought to optimise chemotherapy delivery in this cohort and demonstrated that upfront dose reductions do not reduce progression-free survival in OG cancers. We analysed the treatment and outcome of elderly patients undergoing first-line palliative chemotherapy at our centre, with or without comprehensive geriatric assessment (CGA). Methods: We retrospectively analysed the records of patients over the age of 75 treated at our centre between May 2011 and March 2023. Progression-free survival (PFS) was calculated from the date of treatment initiation to date of radiological progression, or 19 th March 2024 if patients had not progressed. Overall survival (OS) was calculated from treatment initiation to date of death per the electronic health record, or 19 th March 2024 if patients had not died. Grade 3 (G3) toxicities and dose reductions (DRs) were identified from medical records. Statistical analyses were performed using R v4.3.3. Results: 82 patients were included in the analysis. Overall median PFS was 6.5 months (1-107 months) and median OS was 10 months (1-107 months). Patients who qualified for chemotherapy with immunotherapy had improved PFS (median 16 months, range 2-27 months) and OS (median 16 months, range 10-27 months). G3 toxicities were increased in patients without upfront DR (44% vs. 30%). The most significant predictor for survival in multivariate analysis was performance status (PS), which was associated with worse PFS (hazard ratio 2.66, range 1.35–5.35, p = 0.004), and OS (hazard ratio 6.13, range 2.79–13.44, p &lt; 0.001). Age was not associated with survival. Consistent with the GO2 trial, there was no association between upfront DR and PFS (p = 0.13) or OS (p = 0.72). 38% of patients underwent CGA as part of their workup for chemotherapy. These patients were more likely to have upfront DR (61% vs. 47%). In this cohort, G3 toxicity rates were comparable in patients with PS 0-1 who underwent CGA (39% vs. 35%). In patients with PS ≥ 2, G3 toxicity rates were higher in those who did not undergo CGA (67% vs. 30%). Conclusions: Upfront DR in elderly patients is safe and does not impact survival but does reduce the burden of toxicity. PS, rather than age, is a better predictor of survival and treatment outcome. CGA may help mitigate toxicity burden in patients with poor performance status.

Impact of metformin, statins, and beta blockers on survival in patients with primary ovarian cancer: combined analysis of four prospective trials of AGO-OVAR and ENGOT/GCIG collaborators

ObjectiveThe aim of this study was to investigate the association of co-medication with metformin, a statin, or beta blocker with survival in patients with primary ovarian cancer.MethodsIndividual data from three...

Haploidentical transplantation with post-transplant cyclophosphamide versus single cord blood transplantation in adults with relapsed/refractory non-Hodgkin lymphoma.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for relapsed or refractory non-Hodgkin lymphoma (R/R NHL). Allo-HSCT using post-transplant cyclophosphamide (PTCY-haplo) and umbilical cord blood transplantation (uCBT) are important donor options in the absence of matched related siblings. However, the data comparing these two donor sources in R/R NHL are limited. Using the Japanese nationwide transplantation registry data, we identified 857 patients with R/R NHL, including 169 patients who received PTCY-haplo and 688 who received uCBT for their first allo-HSCT between January 2013 and December 2021; 514 patients (60%) had B-cell lymphoma. More PTCY-haplo recipients received allo-HSCT using a reduced-intensity conditioning regimen in recent years. The 3-year overall survival (OS), progression-free survival (PFS), and graft-versus-host disease (GVHD)-free/relapse-free survival (GRFS) rates in the PTCY-haplo and uCBT groups were 44% versus 39% (P = 0.326), 34% versus 33% (P = 0.660), and 19% versus 23% (P = 0.910), respectively; the adjusted hazard ratios for OS, PFS, and GRFS were 0.89 (95% confidence interval: 0.69-1.15, P = 0.373), 0.98 (0.78-1.22, P = 0.852), and 0.92 (0.83-1.21, P = 0.920), respectively. The PTCY-haplo group showed faster neutrophil and platelet engraftment and a lower incidence of grade III-IV acute GVHD. Thus, PTCY-haplo and uCBT could serve as alternative donor sources in patients with R/R NHL.

Osimertinib after definitive chemoradiotherapy in unresectable stage III epidermal growth factor receptor-mutated non-small-cell lung cancer: analyses of central nervous system efficacy and distant progression from the phase III LAURA study

Distant metastases in non-small-cell lung cancer (NSCLC) are a poor prognostic factor that negatively impact quality of life. The central nervous system (CNS) is a common site of distant progression in epidermal growth factor receptor-mutated (EGFRm) NSCLC. Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor recommended for advanced EGFRm NSCLC and as adjuvant treatment for resected EGFRm NSCLC. In LAURA (NCT03521154), osimertinib demonstrated statistically significant improvement in progression-free survival (PFS) versus placebo in unresectable stage III EGFRm NSCLC without progression during/following chemoradiotherapy (CRT). CNS efficacy and time to death or distant metastases (TTDM) analyses are reported here. Patients without progression during/following definitive platinum-based CRT were randomised 2 : 1 to receive osimertinib (80 mg daily) or placebo until progression [by blinded independent central review (BICR)] or discontinuation. The primary endpoint was PFS by BICR. CNS PFS by neuroradiologist BICR and TTDM by BICR were secondary endpoints. Overall, 216 patients were randomised (143 osimertinib, 73 placebo). Median CNS PFS by neuroradiologist BICR was not reached [95% confidence interval (CI) not calculable (NC)-NC] with osimertinib versus 14.9 months (95% CI 7.4 months-NC) with placebo; hazard ratio (HR) for CNS PFS: 0.17 (95% CI 0.09-0.32). CNS PFS analysis by investigator assessment was consistent with BICR assessment. The cumulative incidence of CNS progression at 12 months was 9% (95% CI 5% to 14%) with osimertinib and 36% (95% CI 24% to 47%) with placebo. There was clinically meaningful improvement in TTDM with osimertinib versus placebo; HR for TTDM: 0.21 (95% CI 0.11-0.38). The cumulative incidence of distant metastases at 12 months was 11% (95% CI 6% to 17%) with osimertinib and 37% (95% CI 26% to 48%) with placebo. Osimertinib demonstrated clinically meaningful improvements in CNS PFS and TTDM versus placebo, supporting osimertinib post-CRT as the standard of care in unresectable stage III EGFRm NSCLC.

Results from the randomized KEYNOTE-355 study of pembrolizumab plus chemotherapy for Asian patients with advanced TNBC

In the phase 3 KEYNOTE-355 study (NCT02819518), pembrolizumab plus chemotherapy demonstrated statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) versus placebo plus chemotherapy among patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) and programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 10 tumors. We analyzed outcomes for the subgroup of patients enrolled in Asia in KEYNOTE-355. Patients received pembrolizumab 200 mg or placebo (2:1 randomization) every 3 weeks for 35 cycles plus investigator’s choice chemotherapy. Primary endpoints were PFS per Response Evaluation Criteria in Solid Tumors version 1.1 and OS. Among patients enrolled in Hong Kong, Japan, Korea, Malaysia and Taiwan (pembrolizumab plus chemotherapy, n = 113; placebo plus chemotherapy, n = 47), 117 (73.1%) had PD-L1 CPS ≥ 1 and 56 (35.0%) had PD-L1 CPS ≥ 10. Median time from randomization to data cutoff (June 15, 2021) was 43.8 (range, 36.8‒53.2) months (intent-to-treat [ITT] population). Hazard ratios (HRs [95% CI]) for PFS in the CPS ≥ 10, CPS ≥ 1, and ITT populations were 0.48 (0.24‒0.98), 0.58 (0.37‒0.91), and 0.66 (0.44‒0.99), respectively. Corresponding HRs (95% CI) for OS were 0.54 (0.28‒1.04), 0.62 (0.40‒0.97), and 0.57 (0.39‒0.84). Grade 3/4 treatment-related adverse events (AEs) occurred in 77.9% versus 78.7% of patients with pembrolizumab plus chemotherapy versus placebo plus chemotherapy. No grade 5 AEs occurred. Clinically meaningful improvement in PFS and OS with manageable toxicity were observed with pembrolizumab plus chemotherapy versus placebo plus chemotherapy in patients enrolled in Asia with previously untreated, inoperable or metastatic TNBC.Trial registration: ClinicalTrials.gov, NCT02819518.

Modeling First-Line Daratumumab Use for Newly Diagnosed, Transplant-Ineligible, Multiple Myeloma: A Cost-Effectiveness and Risk Analysis for Healthcare Payers.

This study aimed to assess the cost-effectiveness of two regimens regarded as the standard of care for the treatment of newly diagnosed, transplant-ineligible multiple myeloma in Singapore: (1) daratumumab, lenalidomide, and dexamethasone and (2) bortezomib, lenalidomide, and dexamethasone. Additionally, it aimed to explore potential strategies to manage decision uncertainty and mitigate financial risk. A cost-effectiveness analysis from the healthcare system perspective was conducted using a partitioned survival model to estimate lifetime costs and quality-adjusted life years (QALYs) associated with daratumumab-based treatment and the bortezomib-based regimen. The analysis used data from the MAIA and SWOG S0777 trials and incorporated local real-world data where available. Sensitivity analyses were performed to evaluate the robustness of the findings, and a risk analysis was conducted to analyze various payer strategies in terms of their payer strategy and uncertainty burden (P-SUB), which account for the decision uncertainty and the additional cost of choosing a suboptimal intervention. The incremental cost-effectiveness ratio (ICER) for daratumumab, lenalidomide, and dexamethasone (DRd) compared with bortezomib, lenalidomide, and dexamethasone (VRd) was US $90,364 per QALY gained. The results were sensitive to variations in survival for DRd, postprogression treatment costs, cost of hospice care, and hazard ratio for progression-free survival. The scenarios explored indicated that structural assumptions, such as the time horizon of the analysis, significantly influenced the results due to uncertainties arising from immature trial data and treatment efficacy over time. Among the various payer strategies compared, an upfront price discount for daratumumab emerged as the best approach with the lowest P-SUB at US $14,708. In conclusion, this study finds that daratumumab as a first-line treatment for myeloma exceeds the cost-effectiveness threshold considered in this evaluation. An upfront price reduction is the recommended strategy to manage uncertainties and mitigate financial risks. These findings highlight the importance of targeted payer strategies to address specific types and sources of uncertainty.