Overall Survival Benefit In Patients Research Articles

Conventional versus high-dose salvage chemotherapy for relapsed testicular germ cell tumours

Since the introduction of cisplatin-based combination chemotherapy, patients with metastatic germ cell tumours achieve very high cure rates of >80%. Nevertheless, about 30% of patients relapse despite guideline-endorsed first-line treatment. Of these, again about 50% of patients can still achieve cure with platinum-based salvage chemotherapy and eventually post-chemotherapy residual mass resection.Salvage chemotherapy generally involves platinum-based combination chemotherapy, either as conventional dose cisplatin-based combinations again or as high-dose chemotherapy with subsequent autologous stem cell transplantation.To date, high level evidence from randomised trials supporting the use of salvage high-dose chemotherapy for all patients relapsing after first-line treatment remains lacking, but a large international retrospective registry study had shown a 15% overall survival benefit for patients undergoing salvage high-dose chemotherapy.In this article, we summarise the available literature on the different salvage treatment approaches and discuss these in the light of current treatment guideline recommendations for the management of testicular cancer.

Oncological and Survival Outcomes of Pelvic Lymph Node Dissection in Patients with Non-Muscle Invasive Bladder Cancer Undergoing Radical Cystectomy using the National Cancer Database

ObjectiveTo evaluate the role of pelvic lymph node dissection (PLND) in patients diagnosed with high-risk non-muscle-invasive bladder cancer (NMIBC) undergoing radical cystectomy (RC) using a national cohort of NMIBC patients. MethodsA cohort of patients diagnosed with NMIBC cancer with urothelial carcinoma from the National Cancer Database (NCDB) between 2004 and 2019 was utilized. The cohort consists of patients who have not received BCG and underwent upfront radical cystectomy or pelvic exenteration. Kaplan Meier analysis was utilized to assess overall survival (OS) outcomes. Cox regression was also utilized to identify independent predictors of OS. ResultsThe cohort of 9399 patients was stratified by clinical T stage and then subdivided by pathological outcome. For patients with cTa, a majority received a lymph node dissection 97.74% (941/1019), amongst the entire cohort, a minority had node positive disease 3.3% (34/1019). For cTis, most patients received a lymph node dissection 94.08% (482/507), and a minority had node positive disease 5.1% (26/507). For cT1, most patients had a lymph node dissection 95.62% (6,060/6,337), and a 13.1% (832/6,337) of patients had a positive lymph node. Amongst patients with cT1 disease who underwent PLND, KMA demonstrated better OS compared to patients who did not undergo PLND (p <0.001). ConclusionThe data suggests an OS benefit in patients with later stage (cT1) NMIBC. Thus, our findings support the existing clinical guidelines of pelvic lymph node dissection in patients with high-risk non-muscle invasive bladder cancer.MicroAbstractTo elucidate the role of pelvic lymph node dissection (PLND) in treating non-muscle-invasive bladder cancer, we utilized a national cohort of 9,399 patients. We used Kaplan-Meier analysis (KMA) to assess overall survival (OS) outcomes. KMA demonstrated improved OS in patients with cT1 disease who underwent PLND compared to patients who did not undergo PLND. Our results confirm existing clinical guidelines.

Recent Advances of Neoadjuvant Immunotherapy for Urothelial Bladder Cancer.

Urothelial bladder cancer is one of the most common malignant tumors of the urinary system, which accounts for 90~95% of urothelial carcinoma. Despite the current standard neoadjuvant management for localized urothelial MIBC (T2-4cN0M0) is cisplatin-based chemotherapy before radical cystectomy, there still had poor performances and less overall survival benefits in patients with localized urothelial MIBC. Moreover, nearly half of MIBC patients were ineligible for receiving cisplatin because of chronic kidney disease and performance status. Although immunotherapy, immune checkpoint inhibitors (ICIs) has been identified as first or second-line treatments for localized and metastasis bladder cancer based on less adverse reactions and favorable outcomes, neoadjuvant immunotherapy had rarely used for the treatment of these patients because of less large-scale clinical randomized studies and limited outcomes. Therefore, we reviewed the advances of efficacy and safety with neoadjuvant immunotherapy for urothelial bladder cancer depended on published articles and clinical studies, which could provide more theoretical evidences and promising strategy for clinical therapeutic development.

Palliative surgery versus non-surgery of the solitary metastatic lesion in De novo metastatic breast cancer: A SEER based study.

This study aimed to evaluate whether palliative surgery for metastatic lesion could provide a survival benefit in metastatic breast cancer (MBC) patients with solitary metastasis. De novo MBC patients with solitary distant lesions were enrolled utilizing the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was conducted to form matched pairs of the surgery group and the non-surgery group. The breast cancer-specific survival (BCSS) and overall survival (OS) outcomes between the 2 groups were compared in the following 3 sample models: the entire cohort of MBC (7665 cases); subgroups of patients with different isolated metastatic organs; and subgroups of patients with different molecular subtypes for each isolated metastatic organ. Compared with the Non-surgery group, the surgery group showed better BCSS and OS before PSM (HR = 0.88, 95% CI = 0.79-0.99, P = .04 and HR = 0.85, 95% CI = 0.76-0.95, P = .006, respectively). After PSM, palliative surgery still provided an OS benefit in patients with brain metastasis and lung metastasis (HR = 0.59, 95% CI = 0.37-0.95, P = .01 and HR = 0.64, 95% CI = 0.45-0.90, P = .02, respectively). Likewise, a better BCSS benefit was also found in the subset of patients with brain metastasis (HR = 0.61, 95% CI = 0.38-1.00, P = .01). Further stratification analysis indicated that patients with the luminal A subtype with brain metastasis have a better BCSS (HR = 0.36, 95% CI = 0.16-0.79, P = .04) and OS (HR = 0.37, 95% CI = 0.18-0.75, P = .03) after undergoing palliative surgery than nonsurgical treatment. Our study originality showed that palliative surgery for metastatic lesion could improve survival prognosis in patients with special single-organ metastasis and specific molecular subtypes. More clinical studies are needed to determine whether palliative surgery should be performed in MBC patients.

The efficacy and safety study of thymosin α1 combined with PD-1 antibodies as adjuvant therapy in patients with hepatocellular carcinoma with high-risk recurrence factors after radical resection.

e16226 Background: Anti-PD-1 immunotherapy has revolutionized unresectable hepatocellular carcinoma (HCC) treatment. The efficacy of postoperative adjuvant therapy (PAT) using anti-PD-1 in treating HCC is currently the subject of extensive research. This study explored the efficacy and safety of anti-PD-1 antibodies combined with thymosin alpha-1 (Tα1) for patients with HCC and high-risk recurrent factors (HRRFs) post-hepatectomy. Methods: Data from 273 patients with HCC and HRRFs who underwent hepatectomy at Tongji Hospital (January 2019 to July 2022) were prospectively collected. Patients were nonrandomly divided into Tα1+ anti-PD-1 antibodies (65, 23.8%), anti-PD-1 antibodies (84, 30.8%), and control (no adjuvant therapy, 124, 45.4%) groups based on finances and willingness. After propensity score matching (PSM), recurrence-free survival (RFS) and overall survival (OS) were compared. Cox regression analysis identified the RFS- and OS-related prognostic factors, followed by subgroup analysis. Results: After PSM, 65 patients were matched. The anti-PD-1 antibodies + Tα1 group exhibited longer RFS than the anti-PD-1 antibodies (P = 0.014) and control (P &lt; 0.0001) groups. The anti-PD-1 antibodies group had longer RFS than the control group (P &lt; 0.0001). The anti-PD-1 antibodies + Tα1 (P = 0.00049) and anti-PD-1 antibodies groups (P = 0.0041) demonstrated longer OS than the control group. The 1- and 2-year RFS rates in the Tα1 + anti-PD-1 antibodies, anti-PD-1 antibodies, and control groups were 98.4%, 86.2%, and 49.2% (P &lt; 0.001), and 80.2%, 65.8%, and 24.6% (P &lt; 0.001), respectively. The corresponding 1-, 2-, and 3-year OS rates were 100.0%, 100.0%, and 84.6% (P &lt; 0.001), 98.0%, 91.4%, and 69.0% (P &lt; 0.001), and 91.3%, 86.8%, and 57.4% (P &lt; 0.001), respectively. Multivariable analyses suggested that the Tα1 + anti-PD-1 antibodies treatment improved the RFS and OS more than the non-anti-PD-1 antibodies + Tα1 treatment (hazard ratio (HR): 0.174, 95% confidence intervals (CI): 0.089–0.340, P &lt; 0.001 and HR: 0.240, 95% CI: 0.084–0.683, P = 0.008, respectively). Subgroup analysis demonstrated significant RFS and OS benefits for patients with HCC and vascular invasion treated with Tα1 + anti-PD-1 antibodies. Grade 1 and 2 toxicities included rash/pruritus (21.5%), diarrhea (18.5%), and reactive cutaneous capillary endothelial proliferation (RCCEP)(15.4%). Grade 3 toxicities included RCCEP (1.5%), diarrhea (1.5%), rash/pruritus (0.8%), edema (0.8%), hepatitis (0.8%), nausea/vomiting (0.8%), and hypothyroidism (0.8%). No grade 4/5 toxicities or severe adverse events were detected. Conclusions: Combining anti-PD-1 antibodies with Tα1 as adjuvant therapy is safe, improving postoperative prognosis in patients with HCC and HRRFs after hepatectomy, proving more effective than anti-PD-1 antibodies alone.

Effect of Implantable Cardioverter-defibrillators in Nonischemic Heart Failure According to Background Medical Therapy: Extended Follow-up of the DANISH Trial

The Heart Failure Collaboratory (HFC) score integrates types and dosages of guideline-directed pharmacotherapies for heart failure (HF) with reduced ejection fraction (HFrEF). We examined the effects of cardioverter-defibrillator (ICD) implantation according to the modified HFC (mHFC) score in 1116 patients with nonischemic HFrEF from the Danish Study to Assess the Efficacy of ICDs in Patients with Nonischemic Systolic HF on Mortality (DANISH). Patients were assigned scores for renin-angiotensin-system inhibitors, beta-blockers and mineralocorticoid receptor antagonists (0, no use; 1, < 50% of maximum dosage; 2, ≥ 50% of maximum dosage). The maximum score was 6, corresponding to ≥ 50% of maximum dosage for all therapies. The median baseline mHFC score was 4, and the median follow-up was 9.5 years. Compared with an mHFC score of 3-4, an mHFC score of 1-2 was associated with a higher rate of all-cause death (mHFC = 1-2: adjusted HR 1.67 [95% CI, 1.23-2.28]; mHFC = 3-4, reference; mHFC = 5-6: adjusted HR 1.07 [95% CI, 0.87-1.31]). ICD implantation did not reduce all-cause death compared with control (reference) (HR 0.89 [95% CI, 0.74-1.08]), regardless of mHFC score (mHFC = 1-2: HR 0.98 [95% CI, 0.56-1.71]; mHFC = 3-4: HR 0.89 [95% CI,0.66-1.20]; mHFC = 5-6: HR 0.85 [95% CI, 0.64-1.12]; Pinteraction, 0.65). Similarly, ICD implantation did not reduce cardiovascular death (HR 0.87 [95% CI, 0.70-1.09]), regardless of mHFC score (Pinteraction, 0.59). The ICD group had a lower rate of sudden cardiovascular death (HR, 0.60 [95% CI,0.40-0.92]); this association was not modified by mHFC score (Pinteraction, 0.35). Lower mHFC scores were associated with higher rates of all-cause death. ICD implantation did not result in an overall survival benefit in patients with nonischemic HFrEF, regardless of mHFC score.

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

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

Abstract CT215: Frontline vaccination with the B-cell peptide compound HER-Vaxx (IMU-131), combined with standard-of-care chemotherapy induces high levels of HER2-specific antibodies mediating ADCC and intracellular phosphorylation inhibition resulting in overall survival benefit in patients with HER2+ metastatic or advanced gastric/GEJ adenocarcinoma - Final results from Phase II/HERIZON study

Abstract Background: HER2, a member of the epidermal growth factor receptor (EGFR) family, is overexpressed in approximately 30% of gastric cancers. HER-Vaxx is a B cell peptide-based anti-HER2 vaccine (IMU-131) comprising trastuzumab’s binding site. Here, we present the results of the randomized open-label, multicenter phase 2 HERIZON trial (NCT02795988), which compared HER-Vaxx plus chemotherapy to chemotherapy alone. The study aimed to evaluate clinical (primary endpoint) and antibody (secondary endpoint) responses in patients with HER2-overexpressing gastric/gastro-esophageal junction (GC) cancer naïve to anti HER2 therapy. Methods: Patients were randomized to chemotherapy alone (n=17) or HER-Vaxx (50µg, recommended phase 2 dose) plus chemotherapy (n=19). In the HER-Vaxx group, patients received the vaccine at days 0, 14, 35, and 77, then every 63 days until disease progression. Chemotherapy consisted of oxaliplatin plus capecitabine and was started at day 0, repeated every 21 days for a maximum of 6 cycles. The clinical responses were assessed by RECIST 1.1 criteria. FACS analysis of PBMCs for immunophenotyping was carried out, as well as in vitro phosphorylation inhibition assays of HER2 and the signaling pathway kinases Akt and MAPK, and mediation of ADCC to characterize the vaccine-induced IgG antibodies. Results: A 42% survival benefit for patients treated with HER-Vaxx plus chemotherapy [median overall survival: 13.9 months (7.5, 14.3)] compared to chemotherapy alone [mOS: 8.3 months (6.0, 9.6)] was shown, which translated into an OS HR of 0.580 (80% 2-sided CI: 0.362, 0.927). A highly significant HER2-specific IgG and IgG1 antibody response at all time points, particularly after 3 or more doses of HER-Vaxx were induced (P&amp;lt;0.001). The HER-Vaxx antibody response correlated well with mediating ADCC (IgG, P=0.003; IgG1, P=0.05) and the anti-tumor effect (IgG, P=0.001; IgG1, P=0.016). Moreover, the HER-Vaxx-induced IgG antibodies exhibited binding to the gastric cancer cell line N87, with capacity to inhibit HER2 signaling pathway kinases Akt and MAPK phosphorylation. It also demonstrated decreased levels of Foxp3+ Tregs (P=0.0013). Conclusions: The previously shown safety profile of HER-Vaxx, along with the improved clinical and antibody responses in HER2-overexpressing GC patients shown here, validate the proof of concept for a first-in-class B-cell immunotherapy based on HER2 B-cell peptides. Clinical trials evaluating further treatment with HER-Vaxx in HER2+ GC are ongoing. Citation Format: Joshua Tobias, Michael Kundi, Erika Garner-Spitzer, Christoph Zielinski, Marina Maglakelidze, Zoran Andric, Zoran Petrovic, Rajnish Nagarkar, Tanuj Chawla, Leslie Mi Ok Chong, Bonnie Nixon, Sharon Yavrom, Nicholas J. Ede, Ursula Wiedermann. Frontline vaccination with the B-cell peptide compound HER-Vaxx (IMU-131), combined with standard-of-care chemotherapy induces high levels of HER2-specific antibodies mediating ADCC and intracellular phosphorylation inhibition resulting in overall survival benefit in patients with HER2+ metastatic or advanced gastric/GEJ adenocarcinoma - Final results from Phase II/HERIZON study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT215.

Osimertinib in the treatment of resected EGFR-mutated non-small cell lung cancer: a cost-effectiveness analysis in the United States.

Background: In the double-blind phase III ADAURA randomized clinical trial, adjuvant osimertinib showed a substantial overall survival benefit in patients with stage IB to IIIA, EGFR-mutated, completely resected non-small cell lung cancer (NSCLC). We conduct a cost-effectiveness analysis comparing the use of adjuvant osimertinib to placebo in patients with stage IB to IIIA, EGFR-mutated, resected NSCLC. Methods: Based on the results obtained from the ADAURA trial, a Markov model with three-state was employed to simulate patients who were administered either osimertinib or placebo until disease recurrence or completion of the study period (3 years). Quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER) were calculated with a willingness-to-pay (WTP) threshold of $150,000 per QALY. Both univariate and probabilistic sensitivity analyses were carried out to explore the robustness of the model. Results: Osimertinib produced additional 1.59 QALYs with additional costs of $492,710 compared to placebo, giving rise to ICERs of $309,962.66/QALY. The results of the univariate sensitivity analysis indicated that the utility of disease-free survival (DFS), cost of osimertinib, and discount rate had the greatest impact on the outcomes. Probabilistic sensitivity analysis showed that osimertinib exhibited a 0% chance of being considered cost-effective for patients using a WTP threshold $150,000/QALY. Conclusion: In our model, osimertinib was unlikely to be cost-effective compared to placebo for stage IB to IIIA, EGFR-mutated, completely resected NSCLC patients from the perspective of a U.S. payer at a WTP threshold of $150,000 per QALY.

Ribociclib plus Endocrine Therapy in Early Breast Cancer

BackgroundRibociclib has been shown to have a significant overall survival benefit in patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer. Whether this benefit in advanced breast cancer extends to early breast cancer is unclear.MethodsIn this international, open-label, randomized, phase 3 trial, we randomly assigned patients with HR-positive, HER2-negative early breast cancer in a 1:1 ratio to receive ribociclib (at a dose of 400 mg per day for 3 weeks, followed by 1 week off, for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI; letrozole at a dose of 2.5 mg per day or anastrozole at a dose of 1 mg per day for ≥5 years) or an NSAI alone. Premenopausal women and men also received goserelin every 28 days. Eligible patients had anatomical stage II or III breast cancer. Here we report the results of a prespecified interim analysis of invasive disease–free survival, the primary end point; other efficacy and safety results are also reported. Invasive disease–free survival was evaluated with the use of the Kaplan–Meier method. The statistical comparison was made with the use of a stratified log-rank test, with a protocol-specified stopping boundary of a one-sided P-value threshold of 0.0128 for superior efficacy.ResultsAs of the data-cutoff date for this prespecified interim analysis (January 11, 2023), a total of 426 patients had had invasive disease, recurrence, or death. A significant invasive disease–free survival benefit was seen with ribociclib plus an NSAI as compared with an NSAI alone. At 3 years, invasive disease–free survival was 90.4% with ribociclib plus an NSAI and 87.1% with an NSAI alone (hazard ratio for invasive disease, recurrence, or death, 0.75; 95% confidence interval, 0.62 to 0.91; P=0.003). Secondary end points — distant disease–free survival and recurrence-free survival — also favored ribociclib plus an NSAI. The 3-year regimen of ribociclib at a 400-mg starting dose plus an NSAI was not associated with any new safety signals.ConclusionsRibociclib plus an NSAI significantly improved invasive disease–free survival among patients with HR-positive, HER2-negative stage II or III early breast cancer. (Funded by Novartis; NATALEE ClinicalTrials.gov number, NCT03701334.)

Survival benefit and clinical characteristics of patients with metastatic colorectal cancer (mCRC) receiving pulmonary metastasectomy.

59 Background: The role of lung metastasectomy in mCRC remains a topic of particular controversy, being uncertain which patients benefit more from it and whether it leads to better survival outcomes. Our aim was to identify clinical and molecular differences and survival data in a cohort from a tertiary care hospital. Methods: We retrospectively analyzed 115 patients with lung metastases from colorectal cancer (CRC) in a tumor registry from 2015 to 2021, analyzing clinical and molecular characteristics, as well as overall survival (OS) data of patients who received lung metastasectomy versus patients who did not. Results: Among all patients, 36 (31.3%) received pulmonary metastases surgery. Patients undergoing metastases resection had more frequently ECOG 0 (51.4% vs 20.8%, p = 0.0011), resected primary tumor (100% vs 78.5%, p = 0.0026), metachronous metastatic disease (75% vs 46.8%, p = 0.0048) and a single metastatic location (79.4% vs 41%, p = 0.0002). In addition, none of them had BRAF mutation (0% vs 17.1%, p = 0.04); however, no statistically significant differences were found regarding KRAS, NRAS, PI3K, HER2 or presence of microsatellite instability (MSI). Patients who received lung metastasectomy had higher BMI (26.1 vs 24.4, p = 0.037) and lower mean levels of CEA (19.5 vs 142.9, p = 0.007), CA 19.9 (30.6 vs 244.9, p = 0.011) and LDH (159 vs 211.9, p = 0.018). We found an OS benefit in patients undergoing metastatic surgery (median not reached (NR) vs 41.4 months, HR for death 0.27, 95% CI, 0.14 - 0.53, p &lt; 0.000); a multivariate analysis confirmed that this benefit was independent from the characteristics mentioned above. The median progression-free survival (PFS) after metastases resection was 53.3 months. Conclusions: In our study, patients who were more likely to receive lung metastasectomy were those with ECOG 0, resected primary tumor, metachronous disseminated disease, a single metastatic location, native BRAF mutation status and low CEA, CA 19.9 and LDH levels, with a significant OS benefit associated.

Radiation and systemic immunotherapy for metastatic uveal melanoma: a clinical retrospective review.

Metastatic uveal melanoma (mUM) is a difficult to treat disease. The liver is the primary site of metastasis in most patients, though uveal melanoma spreads widely in advanced disease. The only FDA approved immunotherapy medication for metastatic uveal melanoma is the HLA-A02:01 restricted bispecific T cell engager drug, Tebentafusp. Checkpoint inhibitor strategies and combination approaches have been tried with some limited success. We describe our experience treating patients at the University of Minnesota. Patients were included if they had biopsy-confirmed mUM. Twenty-five (25) patients meeting the criteria were identified. Medical records were reviewed and data extracted for patient baseline characteristics and response to treatments. Median time to metastasis from the time of local therapy to the eye was 14.2 months (IQR; 9.3-22.0), and first site of metastasis was liver in 92% of patients. Two patients (8%) did not receive systemic therapy or radiation therapy for metastatic disease. Twenty-three (92%) patients received systemic therapy, 13 patients (52%) received ipilimumab-nivolumab as the first-line, while 4 patients (16%) received pembrolizumab. Landmark survival analysis by receipt of systemic therapy and radiation therapy treatments within 6 months of biopsy confirmed diagnosis is shown. Twenty patients (80%) received systemic therapy within 6 months of mUM diagnosis. Thirteen patients (52%) received liver directed radiation therapy within 6 months of mUM diagnosis. Within our cohort, there was no overall survival benefit for patients receiving treatment of metastatic disease within 6 months of mUM diagnosis, versus those electing later or no treatment at all. There was remarkable clinical activity of ipilimumab and nivolumab in a subset of patients with mUM, in agreement with prior studies, and metastatic PD-L1 positive tumors were associated with a prolonged survival.

Impact of adjuvant treatment on survival in patients with 2023 FIGO stage IIC endometrial cancer: a retrospective analysis from two tertiary centers in Korea and Taiwan.

In early-stage endometrial cancer, aggressive histologic types (grade 3 endometrioid, serous, clear cell, carcinosarcomas, undifferentiated, mixed, and other unusual types) are associated with an increased risk of distant metastases and worse survival. However, the optimal adjuvant treatment for these patients remains controversial. The present study investigated the outcomes of different adjuvant treatments in patients with 2023 FIGO stage IIC endometrial cancer. We retrospectively identified patients with 2023 FIGO stage IIC endometrial cancer who underwent surgery followed by either adjuvant treatment or observation from 2000 to 2020 at two tertiary centers in Korea and Taiwan. Recurrence-free survival (RFS) and overall survival (OS) were evaluated using Kaplan-Meier estimates and Cox proportional-hazards models. We also analyzed recurrence patterns after different adjuvant treatments. A total of 272 patients were identified; 204 received adjuvant treatment postoperatively, whereas 68 only underwent observation. Adjuvant treatment was not associated with improved RFS or OS. Non-endometrioid histologic types (p=0.003) and presence of lymphovascular space invasion (LVSI, p=0.002) were associated with worse RFS, whereas only non-endometrioid histologic types impacted OS (p=0.004). In subgroup analyses, adjuvant treatment improved OS in patients with LVSI (p=0.020) and in patients with both LVSI and grade 3 endometrioid histologic type (p=0.007). We found no difference in locoregional and distant recurrence between patients undergoing adjuvant treatment or observation. In this study, the addition of adjuvant treatment was associated with an OS benefit for patients with LVSI, especially those with grade 3 endometrioid tumors.

Differential prognostic value of tumor and plasma T790M mutations in EGFR TKI-treated advanced NSCLC.

Substitution of methionine for threonine at codon 790 (T790M) of epidermal growth factor receptor (EGFR) represents the major mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small-cell lung cancer. We determined the prognostic impact and association of secondary T790M mutations with the outcomes of osimertinib and chemotherapy. Patients (n = 460) progressing from first-line EGFR-TKI treatment were assessed. Tissue and/or liquid biopsies were used to determine T790M status; post-progression overall survival (OS) was analyzed. Overall, 143 (31.1%) patients were T790M positive, 95 (20.7%) were T790M negative, and 222 (48.2%) had unknown T790M status. T790M status [T790M positive versus T790M negative: hazard ratio (HR) 0.48 (95% confidence interval (CI), 0.32-0.70); p < 0.001, T790M unknown versus T790M negative: HR 1.97 (95% CI, 1.47-2.64); p < 0.001] was significantly associated with post-progression OS. T790M positivity rates were similar for tissue (90/168, 53.6%) and liquid (53/90, 58.9%) biopsies (Fisher's exact test, p = 0.433). Tumor T790M-positive patients had significantly longer post-progression OS than tumor T790M-negative patients (34.1 versus 17.1 months; log-rank test, p = 8 × 10-5). Post-progression OS was similar between plasma T790M-positive and -negative patients (17.4 versus not reached; log-rank test, p = 0.600). In tumor T790M-positive patients, post-progression OS was similar after osimertinib and chemotherapy [34.1 versus 29.1 months; log-rank test, p = 0.900; HR 1.06 (95% CI, 0.44-2.57); p = 0.897]. T790M positivity predicts better post-progression OS than T790M negativity; tumor T790M positivity has a stronger prognostic impact than plasma T790M positivity. Osimertinib and chemotherapy provide similar OS benefits in patients with T790M-positive tumors.

Postoperative Radiation Therapy for Thymic Carcinoma: An Analysis of the International Thymic Malignancy Interest Group/European Society of Thoracic Surgeons Database

IntroductionR0 resection and radiation therapy have been associated with improved overall survival (OS) in patients with thymic carcinoma (TC). Here, we analyzed which subgroups of patients derive the greatest benefit from postoperative radiation therapy (PORT). MethodsClinical, pathologic, treatment, and survival information of 462 patients with TC from the International Thymic Malignancy Interest Group/European Society of Thoracic Surgeons database were analyzed. Variables included age, sex, continent of treatment, paraneoplastic syndrome, carcinoma subtype, tumor size, pathologic Masaoka stage, resection status, and use of chemotherapy. OS was the primary end point using the Kaplan-Meier method. Time to recurrence (TTR) was the secondary end point using a competing risk analysis. A 3-month landmark analysis was performed. ResultsPORT was associated with a significant OS benefit (5-y OS 68% versus 53%, p = 0.002). In patients with R0 resection, PORT was associated with increased OS for advanced (stages III–IV, p = 0.04), but not early (stages I–II, p = 0.14) stage TC. In patients with an R1/2 resection of advanced-stage TC, PORT was associated with significantly longer OS (5-y OS 53% versus 38%; p < 0.001). Subset analyses did not reveal clear associations of PORT with TTR. On multivariable analysis, lower pathologic stage, PORT, and R0 resection status were associated with an OS benefit, whereas only higher age and lower pathologic stage had an association with longer TTR. ConclusionsIn the largest individual patient data set on patients with TC reported to date, PORT was associated with a meaningful OS benefit in patients with advanced-stage TC after an R0 or R1/2 resection.

Adjuvant Sorafenib for Postoperative Patients with Hepatocellular Carcinoma and Macrovascular Invasion.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in Taiwan. Some patients with HCC are diagnosed with macrovascular invasion (MVI), which is associated with a poorer prognosis. In Taiwan, sorafenib is the first-line therapy for patients with advanced HCC. However, the efficacy of adjuvant sorafenib therapy remains unclear for the subset of patients with HCC and MVI who are eligible for surgery. Therefore, we investigated the potential benefit of adjuvant sorafenib therapy for patients with HCC and MVI after surgery. Our study showed that the lack of improved PFS or OS of adjuvant sorafenib challenged the therapeutic benefit of postoperative sorafenib. Alcohol consumption and an α-fetoprotein level of ≥400 ng/mL were independent predictors of overall survival (OS); however, adjuvant sorafenib therapy was not a predictor of progression-free survival (PFS) or OS. In conclusion, our study indicated that adjuvant sorafenib therapy did not provide PFS or OS benefits in patients with HCC and MVI.

A phase II clinical trial evaluating the safety and efficacy of durvalumab as first line therapy in advanced and metastatic non-small cell lung cancer patients with Eastern Cooperative Oncology Group performance status of 2

Approximately 30-40% of patients with advanced and metastatic non-small cell lung cancer (NSCLC) present with an impaired performance status (PS). There are limited prospective data on the safety and efficacy of durvalumab in these patients. In this single-arm phase II clinical trial (NCT02879617), patients with previously untreated Stage IIIB/IV NSCLC and ECOG PS of 2 received durvalumab 1500mg every 28 days until progression or unacceptable toxicity. The primary endpoints were overall survival (OS) and safety determined by grade ≥3 treatment-related adverse events (TRAEs). Between April 2017 and March 2021, 50 patients were enrolled, of whom 47 received durvalumab. With a median follow-up of 28 months, median OS was 6 months (95% CI 4-10). TRAEs grade 3 occurred in nine of 47 patients (19%, 95% CI 9%-33%). OS in patients with a PD-L1 TPS of 0, 1-49%, and ≥50% was six months (95% CI 3-15), 11 months (95% CI 4-16), and 11 months (95% CI 0-not reached (NR)), respectively. Health related quality of life (HQRL) assessed at baseline and during therapy demonstrated no statistically significant change over the course of treatment. This study demonstrates that single agent durvalumab is safe and well tolerated in the 1st line treatment of patients with advanced NSCLC and ECOG PS of 2, with an encouraging OS benefit in patients with PD-L1 positive tumors. This trial is amongst the largest prospective studies evaluating durvalumab in the 1st line treatment of advanced stage NSCLC and a PS of2. AstraZeneca, NCI P30CA047904.

Effect of implantable cardioverter-defibrillator in non-ischaemic systolic heart failure according to the Heart Failure Collaboratory Medical Therapy Score: extended follow-up of the DANISH trial

Abstract Background The Heart Failure Collaboratory (HFC) has developed a medical therapy score which integrates types and doses of guideline-directed pharmacotherapies in patients with systolic heart failure, providing a measure of treatment quality. In clinical trials, this score may help determine the additive effect of new treatments. In the Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators (ICDs) in Patients with Non-ischaemic Systolic Heart Failure on Mortality (DANISH) trial, ICD implantation did not provide an overall survival benefit in patients with non-ischaemic systolic heart failure. Purpose Adding four years of additional follow-up to the DANISH trial, we examined the effect of ICD implantation according to baseline modified HFC (mHFC) medical therapy score. Methods In the DANISH trial, 1,116 patients with non-ischaemic systolic heart failure were randomised to receive an ICD (N = 556) or usual clinical care (N = 560, control group). The primary outcome was death from any cause. In the mHFC score, patients were assigned a score for each drug class of the original cornerstones of systolic heart failure treatment (renin-angiotensin-system inhibitor, beta-blocker, and mineralocorticoid receptor antagonist). The maximum score was 100%, corresponding to optimal medical therapy with all three types of medication (=&amp;gt;50% of target dose). Results The median mHFC score at baseline was 67% (25th-75th percentile, 67%-100%; range, 17%-100%). During a median follow-up of 9.5 years, the ICD group did not have significantly lower all-cause mortality compared with the control group (hazard ratio [HR] 0.89 [95% CI, 0.74-1.08]). The results were independent of the mHFC score at baseline (mHFC score = &amp;lt; median: HR 0.91 [95% CI, 0.70-1.19]; mHFC score &amp;gt; median: HR 0.87 [95% CI, 0.66-1.14]; P for interaction, 0.94). Similarly, ICD implantation did not reduce the rate of cardiovascular death overall (HR 0.87 [95% CI, 0.70-1.09]), and this association was not modified by the mHFC score (mHFC score = &amp;lt; median: HR 0.90 [95% CI, 0.65-1.24]; mHFC score &amp;gt; median: HR 0.84 [95% CI, 0.61-1.15]; P for interaction, 0.89). The ICD group had a significantly lower rate of sudden cardiovascular death in the overall population (HR, 0.60 [95% CI, 0.40-0.92]), and this association was not modified by the mHFC score (mHFC score = &amp;lt; median: HR 0.72 [95% CI, 0.40-1.29]; mHFC score &amp;gt; median: HR 0.53 [95% CI, 0.28-0.99]; P for interaction, 0.59). See Figure for results. Conclusions In this extended follow-up study of the DANISH trial, ICD implantation did not provide an overall survival benefit in patients with non-ischaemic systolic heart failure regardless of baseline medical heart failure therapy, assessed by the mHFC score.Modified HFC score in the DANISH trial

Impact of adjuvant chemotherapy on the overall survival of patients with advanced-stage low-grade serous ovarian carcinoma following primary cytoreductive surgery

ObjectiveTo investigate the use and outcomes of adjuvant chemotherapy for patients with advanced-stage low-grade serous ovarian carcinoma following primary cytoreductive surgery.MethodsPatients diagnosed between 2010 and 2015 with International Federation of...

Role of Transarterial Chemoembolization in the Era of Tyrosine Kinase Inhibitor and Immune Checkpoint Inhibitor Combination Therapy for Unresectable Hepatocellular Carcinoma: A Retrospective Propensity Score Matched Analysis

The clinical data of 198 patients diagnosed with unresectable HCC who received a TKI (lenvatinib or sorafenib) plus an ICI (sintilimabor camrelizumab) with or without TACE were retrospectively reviewed between October 2019 and April 2022. Baseline characteristics of the TACE-TKI-ICI group and the TKI-ICI group were matched by propensity score matching in a 1:1 ratio. The tumor response, progression-free survival (PFS), and overall survival (OS) were evaluated and compared between the two groups. After matching, 54 patients were enrolled in each group. The objective response rate (ORR) and disease control rate (DCR) were higher in the TACE-TKI-ICI group (ORR: 63.0% vs. 29.6%, P<0.001; DCR: 85.2% vs. 53.7%, P<0.001). The median PFS was significantly longer in the TACE-TKI-ICI group (9.9 vs. 5.8 months; P=0.026). The median OS between the two groups also reached a significant difference (not reached vs. 18.5 months; P=0.003). In this retrospective study, the results indicated that the addition of TACE to TKI-ICI therapy could contribute to better tumor control, PFS, and OS benefits in patients with unresectable HCC.