12-month Overall Survival Research Articles

Fludarabine melphalan reduced intensity conditioning vs radiation-based myeloablative conditioning in patients undergoing allogeneic transplantation for acute myeloid leukemia with measurable residual disease.

Patients with AML and measurable residual disease (MRD) undergoing allogeneic hematopoietic cell transplantation (HCT) may benefit from myeloablative conditioning (MAC) when feasible to reduce relapse risk. Fludarabine-Melphalan (FluMel) is a common reduced intensity conditioning (RIC) regimen; however, data in MRD+ patients is sparse. We performed a retrospective review of AML patients who underwent their first HCT (2016-2021) without morphologic disease at City of Hope who had pre-transplant marrow evaluated for MRD using multicolor flow cytometry (MFC) and received radiation-based MAC or FluMel conditioning. We identified 312 patients; 44 with MRD+ disease pre-HCT. The 24-month overall survival (OS), leukemia-free survival (LFS) and cumulative incidence of relapse (CIR) were 47.7%, 40.9%, and 38.6% in MRD+, and 78.0%, 73.9%, and 14.6% in MRD- patients. Radiation-based MAC was given to 136 (43.5%) patients (n = 20 with MRD+) and FluMel was given to 174 (55.8%) patients (n = 24 with MRD+). In patients with MRD+, there was no statistically significant difference between those who received MAC vs. FluMel in 24-month OS (60% vs. 38%, p = 0.21), or CIR (35% vs. 42%, p = 0.59), respectively. Our data substantiates the adverse impact of MRD in patients with AML undergoing HCT; FluMel is a reasonable option for MRD+ patients unfit for MAC.

Tremelimumab and durvalumab as neoadjuvant or non-operative management strategy of patients with microsatellite instability-high resectable gastric or gastroesophageal junction adenocarcinoma: the INFINITY study by GONO

BackgroundIn resectable gastric/gastroesophageal junction adenocarcinoma (GAC/GEJAC), microsatellite instability (MSI-H) confers improved survival, but limited benefit from chemotherapy. Immunotherapy may eliminate the need of chemotherapy or surgery. Patients and methodsINFINITY is a multicentre, multicohort phase II trial (NCT04817826) investigating in Cohort 1 the activity and safety of tremelimumab+durvalumab (T300/D) as neoadjuvant treatment for dMMR/MSI-H, resectable GAC/GEJAC. Primary endpoint was pathologic complete response (pCR) rate; Secondary endpoints: progression-free survival (PFS), overall survival (OS), quality of life (QoL), and translational analyses. In Cohort 2, the activity and safety of T300/D was explored as definitive treatment in patients achieving clinical complete response (cCR). Primary endpoint was 2-year cCR rate, Secondary endpoints: PFS, OS, QoL, gastrectomy-free survival (GFS) and translational analyses. ResultsIn Cohort 1, 18 patients were recruited and 15 evaluable. pCR and major-complete pathological response were 60% and 80%. Since pCR rate in T4 tumors was 17%, this subgroup of patients was excluded from enrollment in Cohort 2. At 28.1 months median follow-up, 24-month GC-specific PFS and OS rates were 85% and 92%. In Cohort 2, 18 patients were enrolled and 17 evaluable, 13 had cCR and started non-operative management (NOM). At 11.5 months median follow up, 1 patient had local regrowth and underwent salvage surgery, 12-month GFS was 64.2%. ConclusionsThe INFINITY study provided promising activity results of a chemo-free T300/D combination regimen as pre-operative treatment in dMMR/MSI GAC/GEJAC and the first available feasibility results of a NOM strategy in this disease setting, worth of further validation in larger cohorts.

Spatial interactions of immune cells as potential predictors to efficacy of toripalimab plus chemotherapy in locally advanced or metastatic pancreatic ductal adenocarcinoma: a phase Ib/II trial

Advanced pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. Immunotherapy alone offers limited efficacy, but it is still unknown whether its combination with chemotherapy could offer synergistic anti-tumor effects. This phase Ib/II study evaluated the safety and efficacy of combining toripalimab with the gemcitabine plus nab-paclitaxel (GnP) regimen as first-line treatment for locally advanced or metastatic PDAC and explored predictive biomarkers (ChiCTR2000032293). The primary endpoints were safety and overall survival (OS). The secondary outcomes were objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Immune-related biomarkers including programmed death-ligand 1 (PD-L1) expression, genetic status, cytokine levels, and spatial features of the tumor immune microenviroment (TIME) were investigated. Neither serious treatment-related adverse events nor grade 4 immune-related adverse events were reported. Among the 72 patients, the median OS was 8.9 months, 12-month OS rate was 31.9%, with median PFS of 5.6 months, ORR of 33.3%, and DCR of 90.3%. Higher PD-L1 expression, without liver metastases were associated with higher ORR, however these factors could not effectively distinguish responders and non-responders. Importantly, dendritic cells - T helper cells - cytotoxic T lymphocytes (DC-Th-CTL) enriched immune niche and their spatial interactions were dominant predictors of response based on TIME analysis using a cyclic multiplex tissue staining assay, with an area under the curve value of 0.8. Overall, GnP plus toripalimab exhibited good safety and differentiated efficacy in selected population, and the spatial interactions of DC-Th-CTL represent promising predictors to efficacy of immunochemotherapy in locally advanced or metastatic PDAC.

NIMG-61. TRANSVENTRICULAR MIGRATION OF CESIUM-131 BRACHYTHERAPY SEEDS TO THE SACRAL THECAL SAC IN A PATIENT TREATED FOR RECURRENT GLIOBLASTOMA

Abstract Cesium-131 brachytherapy (GammaTileTM) is a relatively new form of surgically targeted radiation therapy for recurrent glioblastoma. While seed migration is a well-documented complication of solid tumor brachytherapy, it has not been reported in the treatment of glioblastoma. Here, we describe a rare occurrence of seed migration in a 71-year-old patient treated for recurrent left temporal lobe glioblastoma. The GammaTile is comprised of a resorbable collagen matrix containing four titanium-encapsulated radioactive Cs-131 seeds. Each seed emits a localized dose of radiation with a 9.7-day half-life. To prevent displacement from the resection cavity, oxidized regenerated cellulose (SurgicelTM) was applied to the cavity surface under the tiles and fibrin sealant (TisseelTM) was applied over the tiles. Margins of the lateral ventricles were not breached during the surgery and surface was non-ulcerated. The tiles remained in place on follow-up imaging for at least 7 weeks. At least 97% of the prescribed dose was delivered before seed migration. Bevacizumab systemic treatment was initiated. Abdominal CT obtained after 3 months incidentally noted migration of 2 seeds to the sacral spinal canal. Additional seeds had migrated to the suprasellar region, left lateral ventricle, and lateral cerebellomedullary cistern. Despite seed migration, the patient maintained progression-free survival for at least 10 months, with at least 30 months of overall survival from the time of diagnosis. Although the patient did not experience any symptoms related to seed migration, this has the potential to cause radiation-related toxicity to healthy tissue, particularly if it occurs early after surgery. The use of bevacizumab may have contributed to penetration of the lateral ventricle. Despite meticulous surgical technique, the potential for seed migration should be considered during treatment planning when using anti-angiogenic therapies. Further research is needed to better understand the factors contributing to seed migration and to develop strategies for minimizing this risk.

SURG-53. LONG TERM FOLLOW-UP OF RESECTION PLUS CESIUM-131 BRACHYTHERAPY FOR PREVIOUSLY IRRADIATED RECURRENT BRAIN METASTASES

Abstract BACKGROUND Recurrent brain metastases (rBM) after previous radiosurgery present a clinical dilemma, as the advantages of reirradiation need to be weighed against the potential of significant radiation toxicity. Salvage resection with Cs-131 brachytherapy offers improved dosimetry due to reduced integral dose to healthy brain compared to repeat radiosurgery. We previously reported initial results of rBM treated with resection and salvage Cs131 brachytherapy; we present an updated analysis of tumor control with extended follow-up. METHODS We analyzed consecutive patients with rBM previously treated with radiosurgery, who underwent salvage resection plus implantation of Cs131 seeds (GammaTile, GT Medical Technologies). The prescribed brachytherapy dose was 60 Gy at 5mm from the cavity. Median follow-up was calculated using reverse Kaplan-Meier. Local recurrence was defined by new nodular contrast enhancement with hyperperfusion within 5mm of the resection cavity. Marginal recurrence was defined as >5mm but not beyond 1cm from the cavity. Local control and overall survival (OS) from brachytherapy were analyzed using Kaplan-Meier. RESULTS Twenty-five patients underwent Cs131 implantation in 30 tumor cavities. The median presurgical rBM maximal diameter was 2.95 cm (range 1.1-6.3). The most common histology was lung adenocarcinoma (n=8, 27%) followed by breast (n=7, 23%) and renal cell (n=3, 10%). Radiographic gross- or near-total resection was achieved in 80% of lesions. The median number of Cs131 seeds implanted was 17, (range 6-30), (median strength 3.5 U/seed). With median follow-up of 37 months (95%CI:29-45), twelve and 24-month OS was 55% and 41%, respectively. Four tumors recurred (3 in-field, one marginal) for a 1- and 2-year local control rate of 87% and 81%, respectively. Data for adverse radiation effects is under analysis and will be presented. CONCLUSIONS With over 3 years of follow-up, intraoperative brachytherapy with collagen-embedded Cs131 implants was associated with durable local control for this challenging clinical scenario. A randomized Phase II trial of Cs131 vs. standard of care for rBM (NCT04690348) is actively accruing.

NIMG-08. IMAGING FINDINGS AND PROGNOSTIC FACTORS IN DIFFUSE HEMISPHERIC GLIOMA, H3 G34-MUTANT

Abstract INTRODUCTION Diffuse hemispheric glioma, H3 G34-mutant (DHGs), are a newly categorized tumor in pediatric-type diffuse high-grade gliomas in the 2021 World Health Organization classification, with a poor prognosis. DHGs has been reported to occur in less than 1% of all gliomas, but prognostic factors have not been fully investigated in previous studies due to small sample sizes. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs. METHODS We searched Medline through the PubMed database using two search terms: “G34” and “glioma”, between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan–Meier curves and logistic regression. RESULTS A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS of all cases was 14.4 months. Univariate logistic regression analysis with 12-month OS as the outcome showed that the MI-positive group had a significantly higher mortality than that in the MI-negative group, and the gross total resection achieved group had a significantly lower mortality than that in the group that underwent biopsy alone. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs. CONCLUSIONS Similar to glioblastomas, DHGs have a poor prognosis if they invade deep structures or the contralateral cerebrum; however, safe and maximal tumor resection may prolong survival.

Belumosudil Is Efficacious for the Management of Heavily Pretreated and Prolonged Chronic Graft-Versus-Host Disease: A Retrospective Multi-Center Real-World Study By the Israel Association for Bone Marrow Transplantation and Cellular Therapy

Introduction : Chronic graft-versus-host disease (cGvHD) remains one of the most important complications of allogeneic stem cell transplantation (ASCT) and is a leading cause of morbidity, late non-relapse mortality, and impaired quality of life. Recent advances in understanding the cGVHD mechanisms have led to the development of the Rho-associated coiled-coil containing protein kinase 2 (ROCK-2) selective inhibitor, belumosudil. The pivotal ROCKstar trial demonstrated the efficacy and acceptable safety profile of belumosudil in cGVHD patients, which led to its FDA approval for the use after >2 prior lines of therapy (LOT). The current study aimed to investigate the efficacy and safety of belumosudil in patients with cGVHD in real-world settings across all transplant centers in Israel. Methods : Data on patients treated with belumosudil for cGVHD at 6 adult and 3 pediatric transplant centers via compassionate use programs were collected and analyzed. These data included patient demographics, underlying disease requiring ASCT, transplant details, cGVHD details, and outcomes of belumosudil treatment. Results : Forty-five patients were included in the final analysis: 42 were treated according to FDA indications, and 3 pediatric patients (ages 4, 4, and 6 years) were treated outside the FDA labeled indication. The median age was 46 (range, 4-75) years; 44.4% were females. GVHD prophylaxis included a calcineurin inhibitor and methotrexate in 66.7%, post-transplant cyclophosphamide in 13.3% and others in 20% of patients. Acute GVHD occurred in 48.9% of patients. The majority of patients (84.4%) had severe cGVHD with a median of 4 involved organ systems (range, 1-7) and received a median of 4 prior LOT (range, 2-6). Notably, 86.7% had prior ruxolitinib exposure, and 13.3% concurrently received belumosudil and ruxolitinib. Patients had been treated for cGVHD for a median of 2.3 (range, .08 - 19.1) years prior to belumosudil commencement. The median duration of belumosudil therapy was 7.8 (range: 1.2 - 28.8) months, with 73.3% of patients still on treatment. The median time to best response was 100 days (range: 32 - 328). Response rates were as follows: complete response (CR) 6.7%, partial response (PR) 48.9%, stable disease (SD) 40%, and progressive disease (PD) 4.4%, with an overall response rate (ORR) of 55.6%. Responses for skin cGVHD were: CR - 11.1%, PR - 50%, SD - 38.9%; for lung cGVHD: PR - 44.4%, SD - 48.1%, PD - 7.4%. The median reduction of the glucocorticoid dose was from 0.29 mg/kg/d of prednisone at the beginning of treatment to 0.02 mg/kg/d at the last follow-up or belumosudil cessation. The most common adverse events (AEs) were pulmonary infections (17.8%) and the primary reason for belumosudil discontinuation was cGHVD worsening. Only one patient stopped belumosudil due to AEs. While on treatment, 26.1% of patients had cGVHD progression. Six patients (13.3%) died, three from cGVHD worsening, two from pulmonary infections, and one from relapsed leukemia. At a median follow-up of 8 months (range 1.3-32), the GVHD relapse-free survival (RFS) was 72% (95% CI 59%-85%) and the estimated 12-month GVHD RFS was 66% (95% CI 46%-86%). Overall survival (OS) at 8 months was 92% (95% CI 81%-100%) and the estimated 12-month OS was 75% (95% CI 62%-88%). Conclusions : The findings of this real-world study, while comparable to those observed in the ROCKstar trial, are encouraging, considering the heavily pretreated patient population with prolonged and severe cGVHD. No new safety signals emerged. Future studies are warranted to optimize patient selection and timing for treatment initiation.

Stereotactic arrhythmia radioablation - A systematic review and meta-analysis of the prospective clinical studies

Abstract Background Stereotactic arrhythmia radioablation (STAR) is increasingly being evaluated in prospective studies as a new promising treatment option for patients with therapy-refractory ventricular tachycardia (VT). In STAR, the VT substrate is noninvasively treated with a high dose of radiotherapy. Recently, several single-arm prospective studies evaluating the clinical outcomes of STAR were published. Considering that the evidence base consists mainly of retrospective case series, we conducted a systematic review and meta-analysis to synthesize the prospective data on outcomes of STAR. Purpose To perform a systematic review and meta-analysis of prospective studies evaluating clinical outcomes of STAR for VT. Methods This study was registered in PROSPERO and adhered to the PRISMA reporting guidelines. Full-text studies describing prospective studies evaluating the safety and efficacy of STAR for VT were included in this study. Records published until August 2023 were retrieved from OVID MEDLINE, OVID Embase, Web of Science Core Collection, the Cochrane Central Register of Controlled Trials, and Google Scholar search engine (top 200 hits), deduplicated, and screened for eligibility. Abstract screening, full-text screening, data extraction and quality assessment were performed by two reviewers independently. Endpoints were defined as treatment related CTCAE grade ≥3 adverse events within 90 days after treatment, overall survival (OS), time to VT recurrence, and recurrence-free survival. Rates of patients achieving pre-defined 50%, 75% and 95% VT burden reduction thresholds were summarised. Random-effects generalized linear mixed-effects models and inverse variance models were used for the meta-analysis. Results 1861 records were identified, 987 were screened, and 10 full-text manuscripts published between 2019 and 2023 describing the results of STAR in 82 patients were included in this study. The majority were male (n=72; 88%), between 45 and 85 years old, and suffered from ischaemic cardiomyopathy (n=51; 62%). Median left ventricular ejection fraction ranged from 21 to 38% between studies. 20 patients did not undergo a prior catheter ablation for VT. All patients were treated with a single dose of 25 Gy and median planned target volume ranged from 45 to 198 cc between studies. Pooled 12-month OS rate was 0.73, and the proportion of patients experiencing grade ≥3 adverse events within 90 days after STAR was 0.11 (Figure 1). Reduction in VT burden is shown in Table 1. Although these were not pooled because of large heterogeneity in VT reduction time frame definitions, it can be appreciated that most of the patients experienced a reduction in VT burden. Conclusion The increasing evidence from prospective studies on STAR shows acceptable 12-month OS in a population of patients with advanced heart failure and refractory VT. Moreover, there is a modest rate of high-grade adverse events and most patients experience a reduction in VT burden.

Radiomics-Based Machine Learning with Natural Gradient Boosting for Continuous Survival Prediction in Glioblastoma.

(1) Background: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with an aggressive disease course that requires accurate prognosis for individualized treatment planning. This study aims to develop and evaluate a radiomics-based machine learning (ML) model to estimate overall survival (OS) for patients with GBM using pre-treatment multi-parametric magnetic resonance imaging (MRI). (2) Methods: The MRI data of 865 patients with GBM were assessed, comprising 499 patients from the UPENN-GBM dataset and 366 patients from the UCSF-PDGM dataset. A total of 14,598 radiomic features were extracted from T1, T1 with contrast, T2, and FLAIR MRI sequences using PyRadiomics. The UPENN-GBM dataset was used for model development (70%) and internal validation (30%), while the UCSF-PDGM dataset served as an external test set. The NGBoost Survival model was developed to generate continuous probability estimates as well as predictions for 6-, 12-, 18-, and 24-month OS. (3) Results: The NGBoost Survival model successfully predicted survival, achieving a C-index of 0.801 on internal validation and 0.725 on external validation. For 6-month OS, the model attained an AUROC of 0.791 (95% CI: 0.742-0.832) and 0.708 (95% CI: 0.654-0.748) for internal and external validation, respectively. (4) Conclusions: The radiomics-based ML model demonstrates potential to improve the prediction of OS for patients with GBM.

Stereotactic Radiotherapy Plus Nivolumab in Patients with Locally Advanced Pancreatic Cancer: Results from Phase 1/2 Clinical CA209-9KH Trial.

The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) highlights the urgent need for novel therapeutic strategies. Immune checkpoint inhibitors (ICIs) seem to be ineffective in most PDAC studies. Therefore, we conducted an open-label, multicenter phase 1/2 study (CA209-9KH) to evaluate the safety of stereotactic radiotherapy (SRT) and sequential ICI therapy in PDAC, as well as to validate the efficacy of this regimen as a potential activator of antitumor immunity. Patients aged ≥ 18years with unresectable non-metastatic PDAC following four FOLFIRINOX induction cycles were included. Treatment comprised SRT (4 × 8Gy) and sequential nivolumab administration until disease progression or unacceptable toxicity. The primary endpoints were safety and toxicity assessment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), biomarker evaluation, and quality of life (QoL) analysis. Twenty-two patients were screened, with 15 enrolled. Eleven (median) nivolumab cycles were administered. SRT demonstrated low and clinically nonsignificant toxicity, whereas nivolumab toxicity aligned with prior safety profiles, without grade 4-5 events observed. Three patients discontinued therapy owing to toxicity. Median PFS and OS were 8.1 and 13.0months, respectively, with 12-month PFS and OS rates of 0% and 66.7%, respectively, and a 24-month OS rate of 8.9%. Biomarker levels correlated with clinical or radiological disease control. Patient-reported QoL remained acceptable, deteriorating with disease progression. SRT and nivolumab therapy exhibited manageable toxicity profiles consistent with previous findings; however, long-term treatment responses were not achieved with this regimen in locally advanced PDAC. Another strategy to trigger antitumor immunity in PDAC needs to be sought. EudraCT: 2017-003404-52; ClinicalTrials.gov: NCT04098432.

DKN-01 in Combination With Tislelizumab and Chemotherapy as First-Line Therapy in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: DisTinGuish.

The outcomes of anti-PD-1 agents plus fluoropyrimidine/platinum in frontline advanced gastroesophageal adenocarcinomas (aGEAs) remain poor. We investigated the safety, tolerability, and activity of fluoropyrimidine/oxaliplatin and tislelizumab with the DKK1-neutralizing antibody DKN-01 in aGEAs in a phase IIa open-label study. Patients had untreated human epidermal growth factor receptor 2-negative aGEAs, RECIST v1.1 measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and adequate organ function. Patients received intravenous DKN-01 300 mg once every 2 weeks, tislelizumab 200 mg once every 3 weeks, oxaliplatin 130 mg/m2 once every 3 weeks, and capecitabine 1,000 mg/m2 twice daily on days 1-15 of each 21-day cycle. The primary end point was safety and tolerability. Key secondary end points included objective response rate (ORR) by RECISTv1.1, progression-free survival (PFS), and overall survival (OS). Between September 18, 2020, and April 8, 2021, 25 patients were enrolled. All patients who received at least one dose of DKN-01 were included in the safety analysis. Most patients had gastroesophageal junction tumors, median age was 61 years, 76% were male, and 55% were ECOG of 0. All patients reported at least one treatment-emergent adverse event. The ORR was 73% (95% CI, 49.8 to 89.3), with a disease control rate of 95%. The ORR was 90% (95% CI, 55.5 to 99.7) in the DKK1-high tumor patients and 67% (95% CI, 29.9 to 92.5) in the DKK1-low tumor patients. The median PFS was 11.3 months (95% CI, 5.8 to 12.0) and the 12-month PFS rate was 33%. The median OS was 19.5 months (95% CI, 15.2 to 24.4) with a 12-month OS rate of 76% and an 18-month OS rate of 55%. DKN-01 can be safely combined with frontline fluoropyrimidine/oxaliplatin and tislelizumab and demonstrates encouraging activity independent of PD-L1 expression levels. A randomized phase II trial is ongoing (ClinicalTrials.gov identifier: NCT04363801).

Triple combination of vemurafenib, cobimetinib, and atezolizumab in real clinical practice in the Russian Federation: results of the A1 cohort of the ISABELLA study.

Among several treatment options for BRAF-mutant metastatic melanoma, a combination of BRAF inhibitor, MEK inhibitor, and anti-PDL1 antibody seems to be a new emergent approach recently registered in the Russian Federation. It is still not clear which patient population benefits more from this simultaneous use of three drugs instead of its sequencing. This study aimed to evaluate patients' characteristics treated in real practice in 14 Russian regions by triple combination and to analyze their outcomes depending on biomarkers (PD-L1 expression). This was a part (cohort A1) of a prospective non-interventional study of clinical outcomes and biomarkers in patients with skin melanoma. Patients were included in cohort A1 if combination treatment with vemurafenib (vem) + cobimetinib (cobi) + atezolizumab (atezo) was initiated no earlier than 12 weeks (84 days) prior to written informed consent to participate in this study. The index event was the initiation of therapy with all three drugs vem + cobi + atezo (i.e., triple combination). The primary efficacy endpoint of the study was the 24-month overall survival (OS), defined as the time from the index date to the date of death from any cause. If the patient did not experience an event, the OS will be censored at the date of the last contact. Objective response rate (ORR), duration of response (DoR), and progression-free survival (PFS) in the Intention to treat (ITT) population, in biomarker positive population, and in population with brain metastases were also evaluated. Quality of life questionnaires were pre-planned by protocol if it was a part of routine practice. Adverse events were also collected. Between March 2021 and May 2023, 59 patients were enrolled in 19 centers from 14 regions of Russia. Thirty-one of 59 (52.4%) patients had central nervous system metastases, and 18 of 31 (58.4%) were symptomatic. Forty of 59 patients (68%) received the triple combination as the first-line treatment. The median follow-up period was 16.83 [95% confidence interval (CI) 13.8-19.8] months. The mean duration of therapy with this regimen was 9.95 months (95% CI 7.48-13.8). ORR was 55.1%; progression as the best outcome was seen in 16.3%. The median DoR was 12.95 months (95% CI 11.0-14.8 months), with a median of 20.3 months (95% CI 9.1-31.5 months) when triple therapy was administered in the first-line treatment. In patients with brain metastases (N = 31), ORR was 45.1%; the median DoR was 12.95 (95% CI 11.0-14.8 months). The median PFS in the entire population was 13.6 months (95% CI 8.6-18.6); the 24-month PFS was 22%. The estimated median OS in the entire population was 15.8 months (95% CI NA); 24-month OS was 45% (95% CI 0.32-0.64). In multivariate Cox regression model, biomarkers of interest [lactate dehydrogenase, Programmed cell death ligand-1 (PD-L1)] did not have statistically significant impact on PFS, OS, or DoR probably due to high data missing rate. No unexpected adverse events were reported. Grades 3-4 AEs were seen in 23 of 59 patients (38%) with most common were skin and liver toxicity. Triple combination of atezolizumab, vemurafenib, and cobimetinib had proven its efficacy and tolerability in real settings. No impact of potential predictive biomarkers was seen (NCT05402059).

Pembrolizumab for the First-Line Treatment of Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma: Results from the Single-Arm, Open-Label, Phase III KEYNOTE-913 Study.

The phase III KEYNOTE-913 study was conducted to evaluate the efficacy and safety of pembrolizumab as first-line therapy in patients with advanced Merkel cell carcinoma (MCC). The aim was to report results from the primary analysis of KEYNOTE-913. Patients with recurrent locally advanced or metastatic MCC received pembrolizumab 200mg intravenously every 3weeks for up to 35 treatments (~2 years). The primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary end points were duration of response (DOR) and progression-free survival (PFS) per RECIST v1.1 by BICR, overall survival (OS), and safety and tolerability. Fifty-five patients were treated with pembrolizumab. The median time from first dose to data cutoff (February 15, 2024) was 50.3 months (range 38.7-59.4). The ORR was 49% (95% confidence interval [CI] 35-63), with 12 complete responses and 15 partial responses. The median DOR was 39.8 months (range 4.8-52.5+), and the 24-month DOR rate was 69%. The median PFS was 9.3 months (95% CI 3-26), and the 24-month PFS rate was 39%. The median OS was 24.3 months (95% CI 12.4 to not reached), and the 24-month OS rate was 51%. Any-grade treatment-related adverse events (AEs) occurred in 38 patients (69%); 13 patients (24%) experienced grade 3-5 AEs. The most common treatment-related AEs were fatigue (n = 12 [22%]), pruritus (n = 12 [22%]), and lipase increase (n = 10 [18%]). One patient died of treatment-related Guillain-Barré syndrome. Pembrolizumab provided durable antitumor activity and promising survival and had a manageable safety profile in patients with recurrent locally advanced or metastatic MCC, supporting its use in this population. Clinicaltrials.gov, NCT03783078.

Improved outcomes of palliative radiotherapy combined with immune checkpoint inhibitors in recurrent or metastatic cervical cancers

BackgroundImmunotherapy provides a remarkable survival advantage for patients with recurrent or metastatic cervical cancer (R/M CC). However, the role of immunotherapy in combination with radiotherapy in R/M CC remains unclear. MethodsWe retrospectively analyzed factors affecting immunotherapy effectiveness in patients with R/M CC. Clinical outcomes including tumor response and patient survival were assessed. Kaplan-Meier curves with the log-rank test were employed to compare survival data. Cox regression analysis was utilized to investigate prognostic factors. ResultsA total of 65 R/M CC patients treated with immune checkpoint inhibitors were eligible for analysis. We found that immunotherapy combined with palliative radiotherapy showed a significant positive correlation with complete response (OR = 6.31; 95 %CI: 1.74–22.91; p = 0.005). The 36-month progression-free survival (PFS) rate (73.7 % vs 33.8 %, p = 0.0048) and 36-month overall survival (OS) rate (85.7 % vs 38.7 %, p = 0.0043) were also prominently increased. We further demonstrated that patients prolonged 36-month PFS rate (69.9 % vs 15.2 %; p < 0.001) and 36-month OS rate (64.6 % vs 39.7 %; p = 0.032) when they had more than 4 cycles of immunotherapy. Meanwhile, our findings showed that patients with only recurrence had longer 36-month OS rate (77.7 % vs 44.4 % vs 40.1 %; p = 0.024) compared to those with only metastasis and both. We also observed that patients with squamous carcinoma had higher 2-year PFS rate (57.9 % vs 14.6 %; p = 0.042) than those with other pathological subtypes (adenocarcinoma, adenosquamous carcinoma and neuroendocrine carcinoma). ConclusionsThe combination of immunotherapy and palliative radiotherapy increased complete response rates and improved survivals in recurrent or metastatic cervical cancer patients.

Surufatinib plus toripalimab combined with etoposide and cisplatin as first-line treatment in advanced small-cell lung cancer patients: a phase Ib/II trial

There is still room for improvement in first-line treatment of advanced small cell lung cancer (SCLC). This trial firstly investigated efficacy and safety of antiangiogenic therapy (surufatinib) (200 mg, qd, po) plus anti-PD-1 treatment (toripalimab) (240 mg, d1, ivdrip) combined with etoposide (100 mg/m², d1-d3, iv, drip) and cisplatin (25 mg/m², d1-d3, ivdrip) for advanced SCLC as first-line treatment, which has been registered on ClinicalTrials.gov under the identifier NCT04996771. The four-drug regimen was conducted q3w for 4 cycles with maintenance therapy of surufatinib and toripalimab. The primary endpoint was progression-free survival (PFS). The secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. All of the 38 patients were enrolled for safety analysis, while only 35 patients were enrolled for efficacy analysis since loss of efficacy evaluation in 3 cases after treatment. After a median follow-up of 21.3 months, the ORR was 97.1% (34/35), and the DCR and the tumor shrinkage rate were both 100% (35/35). The median PFS was 6.9 months (95% CI: 4.6 m–9.2 m) and the median OS was 21.1 months (95% CI: 12.1 m–30.1 m). The 12-month, 18-month, and 24-month OS rates were 66.94%, 51.39% and 38.54%. The occurrence rate of grade ≥3 treatment-emergent adverse events (TEAEs) was 63.2% (24/38), including neutrophil count decreased (31.6%, 12/38), white blood cell count decreased (23.7%, 9/38) and platelet count decreased (10.5%, 4/38). No unexpected adverse events occurred. This novel four-drug regimen (surufatinib, toripalimab, etoposide plus cisplatin) revealed impressive therapeutic efficacy and tolerable toxicities.

Epcoritamab in relapsed/refractory large B-cell lymphoma: 2-year follow-up from the pivotal EPCORE NHL-1 trial

Primary results (median follow-up, 10.7 months) from the pivotal EPCORE® NHL-1 study in relapsed or refractory (R/R) large B-cell lymphoma (LBCL) demonstrated deep, durable responses with epcoritamab, a CD3xCD20 bispecific antibody, when used as monotherapy. We report long-term efficacy and safety results in patients with LBCL (N = 157; 25.1-month median follow-up). As of April 21, 2023, overall response rate was 63.1% and complete response (CR) rate was 40.1%. Estimated 24-month progression-free survival (PFS) and overall survival (OS) rates were 27.8% and 44.6%, respectively. An estimated 64.2% of complete responders remained in CR at 24 months. Estimated 24-month PFS and OS rates among complete responders were 65.1% and 78.2%, respectively. Of 119 minimal residual disease (MRD)-evaluable patients, 45.4% had MRD negativity, which correlated with longer PFS and OS. CR rates were generally consistent across predefined subgroups: 36% prior chimeric antigen receptor (CAR) T-cell therapy, 32% primary refractory disease, and 37% International Prognostic Index ≥3. The most common treatment-emergent adverse events were cytokine release syndrome (51.0%), pyrexia (24.8%), fatigue (24.2%), and neutropenia (23.6%). These results underscore the long-term benefit of epcoritamab for treating R/R LBCL with deep responses across subgroups, including patients with hard-to-treat disease and expected poor prognosis (ClinicalTrials.gov Registration: NCT03625037).

Stereotactic radiosurgery for patients with spinal metastases from prostate cancer.

Spinal metastases may result in intractable pain, neurological deficit, and vertebral body collapse. There are only a few studies describing outcomes following spine stereotactic radiosurgery (SRS) specifically for prostate cancer metastases. A prospectively collected database of patients with prostate cancer spinal metastases treated at the University of Pittsburgh Medical Center from 2003 to 2023 was analyzed. The primary outcome was local control (LC). Secondary outcomes were overall survival (OS), pain resolution, and adverse radiation effects (AREs). Thirty-seven patients and 51 lesions were identified. Fifteen lesions (29%) were previously resected and 34 lesions (67%) were previously irradiated. The median tumor volume was 37.0cc (range: 2.9-263.3). A majority of lesions (71%) were treated in a single fraction (median 20Gy, range: 14-22.5); multi-fractionated treatment consisted of 21-30Gy in 2-5 fractions. Median follow-up was 12 months (range: 1-146). The 6-month, 1-year, and 2-year LC rates were 97%, 91%, and 91%, respectively. No tested prognostic factors were associated with LC, including hormone sensitivity. The 6-month, 1-year, and 2-year OS rates were 71%, 56%, and 32%; age > 70 years (p = 0.048) and tumor volume > 30cc (p = 0.03) were associated with inferior rates of OS. Complete or partial pain response was observed in 58% of patients. There were 8 instances (16%) of AREs, 2 of which were vertebral compression fractures (4%). Radiosurgery as a primary or adjuvant treatment modality for prostate cancer spinal metastases confers durable LC and moderate pain relief with minimal toxicity. Further studies are warranted to optimize management in this patient population.

Abstract A087: Clinical outcomes in Black patients with EGFR-mutated NSCLC treated with osimertinib

Abstract Introduction: Epidermal growth factor receptor (EGFR) gene mutations are present in about 15% of non–small cell lung cancer (NSCLC) cases in the U.S. The FLAURA study, in which the tyrosine kinase inhibitor (TKI) Osimertinib demonstrated a median PFS of 18.9 months, set the current standard in the U.S. for front-line treatment of advanced NSCLC with sensitizing EGFR mutations. However, Black patients were greatly underrepresented in the FLAURA study (&amp;lt;1% of trial population) and two retrospective single-institution studies suggest inferior survival in Black patients with EGFR-mutant NSCLC treated with TKIs versus (vs.) other races. Research is needed using large real-world cohorts to evaluate real-world progression-free survival (rwPFS) and overall survival (OS) in Black patients with EGFR-mutant NSCLC to determine whether they derive comparable benefit from Osimertinib as other races. Methods: The nationwide Flatiron Health Electronic Health Record (EHR)-derived de-identified database was used to analyze data from 1503 patients with advanced NSCLC bearing an EGFR exon 19 deletion or L858R mutation who received front-line Osimertinib. The de-identified data originated from 280 US cancer clinics (∼800 sites of care). Patients were stratified by race (Black vs. White) and characteristics were compared using chi-square, Fisher’s exact, and t-tests. Kaplan-Meier curves estimated rwPFS (based on clinician documentation of progression) and OS in months (m). Differences in survival were assessed between Black and White patients using multivariable Cox proportional hazards models that adjusted for age, gender, EGFR subtype, histology, diagnosis year, smoking history, performance status, insurance status, and socioeconomic index. Results: In our cohort, comprised of 179 Black and 1324 White patients with EGFR-mutant NSCLC, median age and percentage with a smoking history did not differ by race. However, Black patients were more likely to be female (74.3% vs. 66.4%, p=0.03), possess an exon 19 deletion tumor (74.3% vs. 58.3%, p&amp;lt;0.001) or be in a low socioeconomic index category (30.2% vs. 8.7%, p&amp;lt;0.001) than White patients. Median rwPFS did not significantly differ between Black and White patients treated with Osimertinib (15.1 m vs. 14.1 m, HR 0.91, p=0.39). Similarly, no significant difference in OS was observed among Black patients treated with Osimertinib as compared to Whites (29.2 m vs. 32.5 m, HR 1.07, p=0.57). Conclusion: This real-world analysis of one of the largest cohorts of Black patients with EGFR-mutant NSCLC to date, did not observe differences in rwPFS and OS as compared to White patients following front-line Osimertinib therapy. Efforts should be made to ensure all patients receive mutational testing upfront so they can receive optimal first line therapy. Citation Format: Neel Belani, Farsha Rizwan, Jill Hasler, Jessica Bauman, Khadijah Mitchell, Hossein Borghaei, Joseph N Bodor. Clinical outcomes in Black patients with EGFR-mutated NSCLC treated with osimertinib [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A087.

A phase II, open-label, single-arm trial of pembrolizumab for recurrent meningioma and solitary fibrous tumor.

Atypical and anaplastic meningiomas account for 20% of all meningioma cases. Solitary fibrous tumor (SFT) is a type of soft tissue sarcoma with similar attributes to meningioma. For patients with refractory or recurrent disease after previous surgery or radiotherapy, there is no effective treatment. Pembrolizumab, an anti-programmed cell death 1 (PD-1) antibody, is an effective treatment for various solid tumors. PD-1 ligand is highly expressed in aggressive meningiomas. We aimed to assess the effectiveness of pembrolizumab in treating meningioma and SFT recurrence after surgery and radiation therapy. This prospective single-arm phase II trial comprised 15 patients with recurrent meningioma and 3 with anaplastic SFT, treated at a single institution during 2018 to 2022. The study was terminated due to a lack of efficacy and slow accrual. The primary endpoint was 6-month progression-free survival (PFS-6). Median progression-free survival (PFS) was 2.6 months, and median overall survival (OS) was 40 months. The 6- and 12-month PFS were both 11.1%. The 6- and 12-month OS were 94.4% and 61.1%, respectively. According to the Response Assessment in Neuro-Oncology (RANO) criteria, the overall response rate was 11%, with 2 patients achieving stable disease and 2 with partial response. Three patients (16.7%) developed grade 3 toxicity. Our results showed that pembrolizumab failed to improve PFS-6 in patients with aggressive meningioma or anaplastic SFT. However, two patients, one with atypical meningioma and one with anaplastic SFT, achieved a partial response. More clinical studies are needed to identify which subset of patients may benefit from this treatment.

The clinical utility of autologous tumor lysate-loaded dendritic cell vaccination for patients with glioma: A systematic review and meta-analysis.

Dendritic cell (DC) vaccines show promise for glioma treatment, but optimal use remains uncertain. This meta-analysis examined DC vaccine efficacy and safety for gliomas. This systematic review and meta-analysis study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. From the date of inception to October 23, 2023, electronic databases PubMed, Embase, Web of Science, and Scopus have been thoroughly evaluated. A total of 12 studies with 998 patients and a mean age ranging from 40.2 to 56 years were included. Across 12 articles, DC vaccine 6-month overall survival (OS) was 100% [95% confidence interval {95%CI}: 100%-100%]. Respectively, 12-month OS reported 75% [95%CI: 65%-85%] but declined to 32% [95%CI: 20%-43%] for 24-month OS. 6- and 12-month progression-free survival reached 49% [95%CI: 21%-77%] and 19% [95%CI:8%-30%]. Studying radiological outcomes shows that complete response and partial response rates were 13% [95%CI: 17%-42%], and 26% [95%CI: 10%-42%], though stable disease reached 33% [95%CI: 15%-51%], suggesting predominant antineoplastic effects. The progressive disease rate also was 24% [95%CI: 9%-57%]. In gliomas, DC vaccinations show a temporary efficacy; stability is more prevalent than regression. Impacts favor decreased resistance to early disease. Enhancing efficacy remains critical. Early therapy can be enhanced by appropriate supplementary therapy integration.