Immune checkpoint inhibitors plus platinum-based chemotherapy compared to platinum-based chemotherapy with or without bevacizumab for first-line treatment of older people with advanced non-small cell lung cancer.

BACKGROUND: Lung cancer is a cancer of the elderly, with a median age at diagnosis of 71. More than one-third of people diagnosed with lung cancer are over 75 years old. Immune checkpoint inhibitors (ICIs) are special antibodies that target a pathway in the immune system called the programmed cell death 1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway. These antibodies help the immune system fight cancer cells by blocking signals that cancer cells use to avoid being attacked by the immune system. ICIs have changed the treatment of people with lung cancer. In particular, for people with previously-untreated advanced non-small cell lung cancer (NSCLC), current first-line treatment now comprises ICIs plus platinum-based chemotherapy, rather than platinum-based chemotherapy alone, regardless of their PD-L1 expression status. However, as people age, their immune system changes, becoming less effective in its T cell responses. This raises questions about how well ICIs work in older adults. OBJECTIVES: To assess the effects of immune checkpoint inhibitors (ICIs) in combination with platinum-based chemotherapy compared to platinum-based chemotherapy (with or without bevacizumab) in treatment-naïve adults aged 65 years and older with advanced NSCLC. SEARCH METHODS: We searched the Cochrane Lung Cancer Group Trial Register, CENTRAL, MEDLINE, Embase, two other trial registers, and the websites of drug regulators. The latest search date was 23 August 2023. We also checked references and searched abstracts from the meetings of seven cancer organisations from 2019 to August 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that reported on the efficacy and safety of adding ICIs to platinum-based chemotherapy compared to platinum-based chemotherapy alone for people 65 years and older who had not previously been treated. All data emanated from international multicentre studies involving adults with histologically-confirmed advanced NSCLC who had not received any previous systemic anticancer therapy for their advanced disease. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were overall survival and treatment-related adverse events (grade 3 or higher). Our secondary outcomes were progression-free survival, objective response rate, time to response, duration of response, and health-related quality of life (HRQoL). MAIN RESULTS: We included 17 primary studies, with a total of 4276 participants, in the review synthesis. We identified nine ongoing studies, and listed one study as 'awaiting classification'. Twelve of the 17 studies included people older than 75 years, accounting for 9% to 13% of their participants. We rated some studies as having 'some concerns' for risk of bias arising from the randomisation process, deviations from the intended interventions, or measurement of the outcome. The overall GRADE rating for the certainty of the evidence ranged from moderate to low because of the risk of bias, imprecision, or inconsistency. People aged 65 years and older The addition of ICIs to platinum-based chemotherapy probably increased overall survival compared to platinum-based chemotherapy alone (hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.70 to 0.88; 8 studies, 2093 participants; moderate-certainty evidence). Only one study reported data for treatment-related adverse events (grade 3 or higher). The frequency of treatment-related adverse events may not differ between the two treatment groups (risk ratio (RR) 1.09, 95% CI 0.89 to 1.32; 1 study, 127 participants; low-certainty evidence). The addition of ICIs to platinum-based chemotherapy probably improves progression-free survival (HR 0.61, 95% CI 0.54 to 0.68; 7 studies, 1885 participants; moderate-certainty evidence). People aged 65 to 75 years, inclusive The addition of ICIs to platinum-based chemotherapy probably improved overall survival compared to platinum-based chemotherapy alone (HR 0.75, 95% CI 0.65 to 0.87; 6 studies, 1406 participants; moderate-certainty evidence). Only one study reported data for treatment-related adverse events (grade 3 or higher). The frequency of treatment-related adverse events probably increased in people treated with ICIs plus platinum-based chemotherapy compared to those treated with platinum-based chemotherapy alone (RR 1.47, 95% CI 1.02 to 2.13; 1 study, 97 participants; moderate-certainty evidence). The addition of ICIs to platinum-based chemotherapy probably improved progression-free survival (HR 0.64, 95% CI 0.57 to 0.73; 8 studies, 1466 participants; moderate-certainty evidence). People aged 75 years and older There may be no difference in overall survival in people treated with ICIs combined with platinum-based chemotherapy compared to platinum-based chemotherapy alone (HR 0.90, 95% CI 0.70 to 1.16; 4 studies, 297 participants; low-certainty evidence). No data on treatment-related adverse events were available in this age group. The effect of combination ICI and platinum-based chemotherapy on progression-free survival is uncertain (HR 0.83, 95% CI 0.51 to 1.36; 3 studies, 226 participants; very low-certainty evidence). Only three studies assessed the objective response rate. For time to response, duration of response, and health-related quality of life, we do not have any evidence yet. AUTHORS' CONCLUSIONS: Compared to platinum-based chemotherapy alone, adding ICIs to platinum-based chemotherapy probably leads to higher overall survival and progression-free survival, without an increase in treatment-related adverse events (grade 3 or higher), in people 65 years and older with advanced NSCLC. These data are based on results from studies dominated by participants between 65 and 75 years old. However, the analysis also suggests that the improvements reported in overall survival and progression-free survival may not be seen in people older than 75 years.

Initial ribociclib plus endocrine therapy for HR+/HER2- advanced breast cancer in pre- and postmenopausal Chinese women: Primary results from a phase 2 randomized study.

BACKGROUND: The MONALEESA­7 and ­2 phase 3 randomized trials demonstrated a statistically significant progression­free survival (PFS) and overall survival (OS) benefit with initial ribociclib + endocrine therapy (ET) versus placebo + ET in pre­ and postmenopausal patients with hormone receptor­positive (HR+)/human epidermal growth factor receptor 2­negative (HER2−) advanced breast cancer (ABC), respectively. Similar trends were observed in Asian subgroup analyses. This phase 2 bridging study of initial ET + ribociclib enrolled pre­ and postmenopausal patients with HR+/HER2­ ABC from China and was conducted to demonstrate consistency of PFS results in a Chinese population relative to the global MONALEESA­7 and ­2 studies. METHODS: Patients were randomized (1:1) to ET (nonsteroidal aromatase inhibitor + goserelin for premenopausal patients; letrozole for postmenopausal patients) + either ribociclib or placebo. The primary endpoint was investigator­assessed PFS. RESULTS: As of April 25, 2022, the median follow­up was 34.7 months in both cohorts. In the premenopausal cohort, median PFS was 27.6 months in the ribociclib arm (n = 79) versus 14.7 months in the placebo arm (n = 77) (hazard ratio 0.67 [95% CI: 0.45, 1.01]). In the postmenopausal cohort, median PFS was not reached in the ribociclib arm versus 18.5 months in the placebo arm (n = 77 in each arm) (hazard ratio 0.40 [95% CI: 0.26, 0.62]). Data also suggested improvements in secondary efficacy endpoints, although OS data were not mature. The safety profile in this population was consistent with that in global studies. CONCLUSIONS: These data demonstrate a favorable benefit­risk profile for ribociclib + ET in Chinese patients.

Neoadjuvant chemoimmunotherapy was associated with better short-term survival of patients with locally advanced esophageal squamous cell carcinoma compared to neoadjuvant chemoradiotherapy.

INTRODUCTION: The chemotherapy and immunotherapy combination is currently the primary strategy to treat metastatic esophageal squamous cell carcinoma (ESCC). Neoadjuvant chemoimmunotherapy (NCIT) is being intensively investigated for treating locally advanced ESCC. OBJECTIVE: We compared the efficacy and safety of NCIT and neoadjuvant chemoradiotherapy (NCRT) to treat locally advanced ESCC. METHODS: We included 214 locally advanced ESCC patients who were administered neoadjuvant therapy from May 2014 to April 2022. The patients were grouped according to two neoadjuvant protocols (NCIT and NCRT) routinely used at our institution. Perioperative findings, pathological results, and survival data were compared between the two groups by conducting unmatched and 1:1 propensity score matching (PSM) analyses. RESULTS: Following 1:1 PSM analysis of the confounders, 66 patients were allocated to each of the two groups. Time span between neoadjuvant therapy completion and esophagectomy was significantly longer after NCRT than that after NCIT (47.1 ± 13.2 days vs. 34.7 ± 8.8 days; p < 0.001). The NCIT group exhibited significantly greater number of harvested lymph nodes than the NCRT group (33.6 ± 12.7 vs. 21.7 ± 10.2; p < 0.001). The pathological complete response and major pathological response rates were similar between the two groups [NCIT group: 25.8% (17/66) and 62.1% (41/66), respectively; NCRT group: 27.3% (18/66) and 56.1% (37/66), respectively (p > 0.05)]. The overall incidence of pneumonia, anastomotic leakage, or postoperative complications did not differ significantly between the two groups. The 2-year cumulative overall survival rates and the 2-year disease-free survival rates of the NCIT and NCRT groups were 80.2% and 62.2%, respectively (p = 0.029) and 70.0% and 50.8%, respectively (p = 0.023). CONCLUSION: In locally advanced ESCC patients, short-term survival after NCIT is superior to that after NCRT, with similar perioperative and pathological outcomes.

Survival by first-line therapy and prognostic group among men with metastatic castration-resistant prostate cancer.

INTRODUCTION: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with prognoses varying from months to years at time of castration-resistant diagnosis. Optimal first-line therapy for those with different prognoses is unknown. METHODS: We conducted a retrospective cohort study of men in a national healthcare delivery system receiving first-line therapy for mCRPC (abiraterone, enzalutamide, docetaxel, or ketoconazole) from 2010 to 2017, with follow-up through 2019. Using commonly drawn prognostic labs at start of mCRPC therapy (hemoglobin, albumin, and alkaline phosphatase), we categorized men into favorable, intermediate, or poor prognostic groups depending on whether they had none, one to two, or all three laboratory values worse than designated laboratory cutoffs. We used Kaplan-Meier methods to examine prostate specific antigen (PSA) progression-free and overall survival (OS) according to prognostic group and first-line therapy, and multivariable cox regression to determine variables associated with survival outcomes. RESULTS: Among 4135 patients, median PSA progression-free survival (PFS) was 6.9 months (95% confidence interval [CI] 6.6-7.3), and median OS 18.8 months (95% CI 18.0-19.6), ranging from 5.7 months (95% CI 4.8-7.0) in the poor prognosis group to 31.3 months (95% CI 29.7-32.9) in the favorable group. OS was similar regardless of initial treatment received for favorable and intermediate groups, but worse for those in the poor prognostic group who received ketoconazole (adjusted hazard ratio 2.07, 95% CI 1.2-3.6). PSA PFS was worse for those who received ketoconazole compared to abiraterone across all prognostic groups (favorable HR 1.76, 95% CI 1.34-2.31; intermediate HR 1.78, 95% CI 1.41-2.25; poor HR 8.01, 95% CI 2.93-21.9). CONCLUSION: Commonly drawn labs at mCRPC treatment start may aid in predicting survival and response to therapies, potentially informing discussions with care teams. First-line treatment selection impacts disease progression for all men with mCRPC regardless of prognostic group, but impacted OS only for men with poor prognosis at treatment start.

Delphi consensus recommendations on treatment for advanced-stage marginal zone lymphoma in South Korea.

Due to the lack of treatment guidelines for the management of advanced-stage marginal zone lymphoma (MZL), only one chemoimmunotherapy-cyclophosphamide, vincristine, and prednisone plus rituximab (R-CVP)-is reimbursed in the first-line setting in South Korea. The aim of this study was to develop a consensus-based recommendation for the treatment of patients with advanced-stage MZL. Twelve hematologist oncologists participated in a two-round Delphi process to identify consensus on the management of patients with advanced-stage MZL in South Korea. Physicians rated their level of agreement with each statement on a four-point Likert scale. Statements were divided into two sections: definitions used in clinical practice and clinical management of patients with advanced-stage MZL. Consensus was reached for 23 of 33 (69.7%) and 5 of 13 statements (38.5%) in rounds 1 and 2, respectively. There was strong consensus (91.7%) that advanced-stage MZL subtypes are defined according to the Lugano staging system. First-line systemic treatment should be prescribed for patients with symptomatic advanced-stage MZL. Although there was unanimous agreement that R-CVP is the standard first-line treatment for advanced-stage MZL, physicians also agreed that bendamustine with rituximab (BR) has greater efficacy than R-CVP as first-line treatment (91.7%). For the treatment of relapsed/refractory advanced-stage MZL, BR and R-CVP can be repeated in patients with short (< 24 months) and long remission periods (≥ 24 months), respectively. This study provides insights on the management of patients with advanced-stage MZL in South Korea. This may enhance clinical decision-making, thus improving patient outcomes.

Phase I studies of davoceticept (ALPN-202), a PD-L1-dependent CD28 co-stimulator and dual PD-L1/CTLA-4 inhibitor, as monotherapy and in combination with pembrolizumab in advanced solid tumors (NEON-1 and NEON-2).

BACKGROUND: Davoceticept (ALPN-202) is an Fc fusion of a CD80 variant immunoglobulin domain designed to mediate programmed death-ligand 1 (PD-L1)-dependent CD28 co-stimulation while inhibiting the PD-L1 and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) checkpoints. The safety and efficacy of davoceticept monotherapy and davoceticept and pembrolizumab combination therapy in adult patients with advanced solid tumors were explored in NEON-1 and NEON-2, respectively. METHODS: In NEON-1 (n=58), davoceticept 0.001-10 mg/kg was administered intravenous either once weekly (Q1W) or once every 3 weeks (Q3W). In NEON-2 (n=29), davoceticept was administered intravenously at 2 dose levels (0.1 or 0.3 mg/kg) Q1W or Q3W with pembrolizumab (400 mg once every 6 weeks). In both studies, primary endpoints included incidence of dose-limiting toxicities (DLT); type, incidence, and severity of adverse events (AEs) and laboratory abnormalities; and seriousness of AEs. Secondary endpoints included antitumor efficacy assessed using RECIST v1.1, pharmacokinetics, anti-drug antibodies, and pharmacodynamic biomarkers. RESULTS: The incidence of treatment-related AEs (TRAEs) and immune-related adverse events (irAEs) was 67% (39/58) and 36% (21/58) with davoceticept monotherapy, and 62% (18/29) and 31% (9/29) with davoceticept and pembrolizumab combination, respectively. The incidence of ≥grade (Gr)3 TRAEs and ≥Gr3 irAEs was 12% (7/58) and 5% (3/58) with davoceticept monotherapy, and 24% (7/29) and 10% (3/29) with davoceticept and pembrolizumab combination, respectively. One DLT of Gr3 immune-related gastritis occurred during davoceticept monotherapy 3 mg/kg Q3W. During davoceticept combination with pembrolizumab, two Gr5 cardiac DLTs occurred; one instance each of cardiogenic shock (0.3 mg/kg Q3W, choroidal melanoma metastatic to the liver) and immune-mediated myocarditis (0.1 mg/kg Q3W, microsatellite stable metastatic colorectal adenocarcinoma), prompting early termination of both studies. Across both studies, five patients with renal cell carcinoma (RCC) exhibited evidence of clinical benefit (two partial response, three stable disease). CONCLUSIONS: Davoceticept was generally well tolerated as monotherapy at intravenous doses up to 10 mg/kg. Evidence of clinical activity was observed with davoceticept monotherapy and davoceticept in combination with pembrolizumab, notably in RCC. However, two fatal cardiac events occurred with the combination of low-dose davoceticept and pembrolizumab. Future clinical investigation with davoceticept should not consider combination with programmed death-1-inhibitor anticancer mechanisms, until its safety profile is more fully elucidated. TRIAL REGISTRATION NUMBER: NEON-1 (NCT04186637) and NEON-2 (NCT04920383).

Histopathological Response to Neoadjuvant Chemotherapy in Patients With Enneking Stage II Conventional Osteosarcoma of Extremities: A Retrospective-Single Institution Study in Vietnam.

BACKGROUND: The standard treatment for localized osteosarcoma is neoadjuvant chemotherapy before surgery, followed by adjuvant chemotherapy. Our aim was to report the rate of histopathological response to neoadjuvant chemotherapy for the treatment of extremity osteosarcoma in Vietnam. METHODS: We performed a retrospective study of stage II conventional osteosarcoma patients under 40 years-old who received MAP regimen as neoadjuvant chemotherapy at the Vietnam National Cancer Hospital between June 2019 and June 2022. Histopathological response was evaluated using the Huvos grading system, in which a good histopathological response was defined as a necrotic rate of 90% or more. RESULTS: Thirty-five eligible patients were included in the study. Male patients accounted for 65.7%, with a median age of 16 years (range, 8-38 years). Of the 35 cases, 31 were reported as stage IIB (88.6%). The femur and tibia were the most common sites in our study, accounting for 51.4% and 34.3%, respectively. The most common pathologic subtype was osteoblastic osteosarcoma (68.6%), followed by chondroblastic subtype (20%). After two cycles of MAP-regimen neoadjuvant chemotherapy, 28 of 35 patients (80%) underwent limb-sparing surgery. A good histopathological response was observed in 18 of 35 patients (51.4%). There were significant correlations between the duration of symptoms (P = 0.016), LDH (P = 0.001) serum levels at initial presentation, and ALP (P = 0.043) serum levels at initial presentation with histopathological response. CONCLUSION: This retrospective study suggests a possible association between symptom duration, pre-treatment LDH levels, and pre-treatment ALP levels with histopathological response rates. Additional clinical investigations with long-term follow-up are needed to investigate survival outcomes in the Asian population.

Long-Term Outcomes of Adjuvant Trastuzumab for 9 Weeks or 1 Year for ERBB2-Positive Breast Cancer: A Secondary Analysis of the SOLD Randomized Clinical Trial.

Importance: The standard adjuvant treatment for patients with ERRB2-positive breast cancer is chemotherapy plus 1 year of trastuzumab. Shorter durations of trastuzumab administration improve cardiac safety, but more information is needed about their effect on survival. Objective: To compare survival outcomes after 9-week vs 1-year administration of trastuzumab with the same adjuvant chemotherapy. Design, Setting, and Participants: This post hoc secondary analysis of an open-label, multicenter, noninferiority-design randomized clinical trial included women aged 18 years or older with early ERBB2-positive, axillary node-negative or axillary node-positive breast cancer who were enrolled from January 3, 2008, to December 16, 2014, at 65 centers in 7 European countries. The current exploratory analysis was conducted after achieving the maximum attainable follow-up data when the last patient enrolled had completed the last scheduled visit in December 2022. Intervention: Chemotherapy consisted of 3 cycles of docetaxel administered at 3-week intervals followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide at 3-week intervals. Trastuzumab was administered in both groups for 9 weeks concomitantly with docetaxel. In the 9-week group, no further trastuzumab was administered after chemotherapy, whereas in the 1-year group, trastuzumab was continued after chemotherapy to complete 1 year of administration. Main Outcomes and Measures: The primary objective was disease-free survival (DFS). Distant DFS and OS were secondary objectives. Survival between groups was compared using the Kaplan-Meier method and log-rank test or univariable Cox proportional hazards regression. Results: Among the 2174 women analyzed, median age was 56 years (IQR, 48-64 years). The median follow-up time was 8.1 years (IQR, 8.0-8.9 years); 357 DFS events and 176 deaths occurred. Trastuzumab for 9 weeks was associated with shorter DFS compared with trastuzumab for 1 year (hazard ratio [HR], 1.36; 90% CI, 1.14-1.62); 10-year DFS was 80.3% in the 1-year group vs 78.6% in the 9-week group. The 5-year and 10-year OS rates were comparable between the 9-week and 1-year groups (95.0% vs 95.9% and 89.1% vs 88.2%, respectively; HR for all time points, 1.20; 90% CI, 0.94-1.54). In multivariable analyses, 9-week treatment was associated with shorter DFS compared with 1-year treatment (HR for recurrence or death, 1.36; 95% CI, 1.10-1.68; P = .005), but there was no between-group difference in OS (HR, 1.22; 95% CI, 0.90-1.64; P = .20). Only 4 patients (0.2%) died of a cardiac cause. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, 1-year vs 9-week adjuvant trastuzumab was associated with improved DFS among patients with ERRB2-positive breast cancer receiving chemotherapy, but there was no significant difference in OS between the groups. Trial Registration: ClinicalTrials.gov Identifier: NCT00593697.

Low-dose abiraterone plus Olaparib as a late-line treatment for mCRPC patients without BRCA1/2 mutations: a multicenter retrospective pilot study.

Although overall survival data are still premature, the PROpel study found radiological progression-free survival (PFS) benefits of abiraterone and olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC). However, for patients who have not been genetically tested or lack BRCA1/2 mutations (BRCAm), this combination therapy has been questioned as a first-line conventional treatment for mCRPC, mainly due to significant health economics and side effects. In our retrospective study, we found that treatment with low-dose abiraterone plus olaparib as a late-line treatment for mCRPC could lead to prostate-specific antigen (PSA) and symptom PFS in selective cases even without BRCAm. The median PSA-PFS was 8 months (IQR: 6.5-11.5), with a median follow-up duration of 39.0 months (IQR: 27.5-64.5). Gene tests were conducted in all patients, identifying non-BRCA mutations through ctDNA testing (24%), tumor tissue testing (12%), or both (64%). Adverse events occurred in 72% of patients, with 16% experiencing Grade ≥ 3 events. Common adverse events included anemia (64%), decreased appetite (48%), and fatigue (25%). Our findings support low-dose abiraterone plus olaparib as a potential option for mCRPC patients without BRCAm, offering manageable safety and efficacy profiles.

[Hodgkin lymphoma - pain at alcohol consumption as the only symptom]. / Diagnostik och behandling av klassiskt Hodgkins lymfom.

The authors Lanke and Relander describe a patient with classical Hodgkin lymphoma (cHL) stage IIA, who had pain at alcohol consumption as the only symptom at diagnosis. The patient was treated with 4 cycles of ABVD chemotherapy and proton therapy 29.75 Gy (RBE). Apart from FDG-PET/CT the course of the disease was followed with serum-TARC. The case illustrates the value of knowing also rare symptoms at the general practice, the usefulness of TARC as a tumour marker in cHL, and the use of proton therapy in order to further reduce late radiotherapy side effects.

Mathematical Modeling of Tumor Immune Interactions: The Role of Anti-FGFR and Anti-PD-1 in the Combination Therapy.

Bladder cancer poses a significant global health burden with high incidence and recurrence rates. This study addresses the therapeutic challenges in advanced bladder cancer, focusing on the competitive mechanisms of ligand or drug binding to receptors. We developed a refined mathematical model that integrates the dynamics of tumor cells and immune responses, particularly targeting fibroblast growth factor receptor 3 (FGFR3) and immune checkpoint inhibitors (ICIs). This study contributes to understanding combination therapies by elucidating the competitive binding dynamics and quantifying the synergistic effects. The findings highlight the importance of personalized immunotherapeutic strategies, considering factors such as drug dosage, dosing schedules, and patient-specific parameters. Our model further reveals that ligand-independent activated-state receptors are the most essential drivers of tumor proliferation. Moreover, we found that PD-L1 expression rate was more important than PD-1 in driving the dynamic evolution of tumor and immune cells. The proposed mathematical model provides a comprehensive framework for unraveling the complexities of combination therapies in advanced bladder cancer. As research progresses, this multidisciplinary approach contributes valuable insights toward optimizing therapeutic strategies and advancing cancer treatment paradigms.

Promising first-line immuno-combination therapies for unresectable hepatocellular carcinoma: A cost-effectiveness analysis.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death all over the world, and brings a heavy social economic burden especially in China. Several immuno-combination therapies have shown promising efficacy in the first-line treatment of unresectable HCC and are widely used in clinical practice. Nevertheless, which combination is the most affordable one is unknown. Our study assessed the cost-effectiveness of the immuno-combinations as first-line treatment for patients with unresectable HCC from the perspective of Chinese payers. METHODS: A Markov model was built according to five multicenter, phase III, open-label, randomized trials (Himalaya, IMbrave150, ORIENT-32, CARES-310, LEAP-002) to investigate the cost-effectiveness of tremelimumab plus durvalumab (STRIDE), atezolizumab plus bevacizumab (A + B), sintilimab plus bevacizumab biosimilar (IBI305) (S + B), camrelizumab plus rivoceranib (C + R), and pembrolizumab plus lenvatinib (P + L). Three disease states were included: progression free survival (PFS), progressive disease (PD) as well as death. Medical costs were searched from West China Hospital, published literatures or the Red Book. Cost-effectiveness ratios (CERs) and incremental cost-effectiveness ratios (ICERs) were evaluated to compare costs among different combinations. Sensitivity analyses were performed to assess the robust of the model. RESULTS: The total cost and quality-adjusted life years (QALYs) of C + R, S + B, P + L, A + B and STRIDE were $12,109.27 and 0.91, $26,961.60 and 1.12, $55,382.53 and 0.83, $70,985.06 and 0.90, $84,589.01 and 0.73, respectively, resulting in the most cost-effective strategy of C + R with CER of $13,306.89 per QALY followed by S + B with CER of $24,072.86 per QALY. Compared with C + R, the ICER of S + B strategy was $70,725.38 per QALY, which would become the most cost-effective when the willing-to-pay threshold exceeded $73,500/QALY. In the subgroup analysis, with the application of Asia results in Leap-002 trial, the model results were the same as global data. In the sensitivity analysis, with the variation of parameters, the results were robust. CONCLUSION: As one of the promising immuno-combination therapies in the first-line systemic treatment of HCC, camrelizumab plus rivoceranib demonstrated the potential to be the most cost-effective strategy, which warranted further studies to best inform the real-world clinical practices.

Toxicity profile of camrelizumab-based immunotherapy in older adults with advanced cancer.

Immune checkpoint inhibitors (ICIs) have become an important cornerstone of many tumour treatments. However, the toxicity profile of immune-chemotherapy combination treatment approaches among older adult cancer patients is still unclear. Patients with any cancer who received camrelizumab-based immunotherapy were eligible for inclusion. The primary endpoints were adverse events (AEs) and immune-related adverse events (irAEs), which were defined based on Naranjo's algorithm. Patients were stratified by age (≥ 70 years and < 70 years), and comparisons were made based on the type of camrelizumab-based therapy (monotherapy, combined chemotherapy, or combined anti-VEGF therapy). A total of 185 patients were administered camrelizumab-based immunotherapy, 55 (30%) of whom were ≥ 70 years old. A total of 146 (78.9%) patients received camrelizumab-based combination treatment. The incidence of all-grade AEs was 56.8% (105 patients), while that of irAEs was 36.8% (68 patients). There was no difference in the percentage of patients experiencing any grade or grade ≥ 3 AEs between age groups. However, the frequency of irAEs (both any grade and grade ≥ 3) significantly differed by age group (P = 0.001 and 0.009, respectively). The results of multivariable analysis revealed that age ≥ 70 years was the only independent risk factor for irAEs. The results of subgroup analysis revealed that the incidence of irAEs was higher in older patients treated with camrelizumab-chemotherapy, while the incidence rates were similar between age groups in the monotherapy and combination anti-VEGF treatment subgroups. Immune-related diabetes mellitus occurred more frequently among older adults. The spectrum of irAEs showed that combination immunotherapy had more widely effects on the organ system than monotherapy. In this study, older (≥ 70 years) patients had a higher risk of all-grade and high-grade irAEs when receiving camrelizumab chemotherapy combination treatment. Notably, long-term random glucose monitoring should be performed during ICI-based immunotherapy in older cancer patients.

Comparative effectiveness analysis of survival with first-line palbociclib or ribociclib plus AI in HR + /HER2- advanced breast cancer (CEPRA study): preliminary analysis of real-world data from Thailand.

BACKGROUND: The current standard first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2 negative (HR + /HER2 -) advanced breast cancer (ABC) is a combination of aromatase inhibitor (AI) plus CDK4/6 inhibitors (CDK4/6i). Direct comparison trials of different CDK4/6i are scarce. This real-world study compared the effectiveness of first-line AI plus ribociclib versus palbociclib. METHODS: This multicenter retrospective cohort study, conducted in six cancer centers in Thailand, enrolled patients with HR + /HER2 - ABC treated with first-line AI, and either ribociclib or palbociclib. Propensity score matching (PSM) was performed. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), time to chemotherapy (TTC), and adverse events. RESULTS: Of the 250 patients enrolled, 134 patients with ribociclib and 49 patients with palbociclib were captured after PSM. Baseline characteristics were well-balanced between groups. Median PFS in patients receiving ribociclib and palbociclib were 27.9 and 31.8 months, respectively (hazard ratio: 0.87; 0.55-1.37). The median OS in the AI + ribociclib arm was 48.7 months compared to 59.1 months in the AI + palbociclib arm (hazard ratio: 0.55; 0.29-1.05). The median TTC in the AI + palbociclib group was 56 months, but not reached in the AI + ribociclib group (p = 0.42). The ORR of AI + ribociclib and AI + palbociclib were comparable (40.5% vs. 53.6%, p = 0.29). Patients receiving palbociclib demonstrated a higher proportion of neutropenia compared to those receiving ribociclib, despite a similar dose reduction rate (p = 0.28). Hepatitis rate was similar between the ribociclib (21%) and palbociclib groups (22%). Additionally, a low incidence of QT prolongation was observed in both the ribociclib (5%) and palbociclib groups (4%). CONCLUSION: This preliminary analysis of a real-world study demonstrated the comparable effectiveness of ribociclib and palbociclib with AI as an initial therapy for HR + /HER2 - ABC. No statistically significant difference in PFS, OS, and TTC was found in patients treated with AI combined with palbociclib or ribociclib. Longer follow-up and further prospective randomized head-to-head studies are warranted.

Comparisons of treatment outcomes of epcoritamab versus chemoimmunotherapy, polatuzumab-based regimens, tafasitamab-based regimens, or chimeric antigen receptor T-cell therapy, in third-line or later relapsed/refractory large B-cell lymphoma.

Many therapies are available for the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥ 2 lines of therapy, albeit with scant evidence on the comparative effectiveness of these therapies. This study used inverse probability of treatment weighting to indirectly compare treatment outcomes of epcoritamab from the EPCORE NHL-1 trial with individual patient data from clinical practice cohorts treated with chemoimmunotherapy (CIT) and novel therapies (polatuzumab-based regimens, tafasitamab-based regimens, and chimeric antigen receptor T-cell [CAR T] therapies) for third-line or later R/R large B-cell lymphoma (LBCL) and DLBCL. In this analysis, epcoritamab demonstrated significantly better response rates and overall survival rates than CIT, polatuzumab-based regimens, and tafasitamab-based regimens. No statistically significant differences in response rates or survival were found for epcoritamab compared with CAR T in R/R LBCL.