Line Systemic Treatment Research Articles

Time from Final Oncologist Visit to Death and Palliative Systemic Treatment Use Near the End of Life in Heavily Pretreated Patients with Luminal Breast Cancer

Background: Palliative care must be tailored for patients with extended disease trajectories, such as those with hormone receptor-positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced breast cancer (ABC), including the appropriate timing of discontinuing treatment. This study aimed to assess the interval between the last oncologist visit and death and the application of systemic treatment near the end of life in this patient population. Methods: This retrospective study included patients with luminal ABC who received at least two lines of palliative systemic treatment at the National Research Institute of Oncology in Poland, and died between November 2020 and March 2024. Results: Seventy-six women, with a median age 62.8 years (range: 35.3–91.5), were included. The median number of prior palliative systemic treatment lines was three (range: 2–6). At their last recorded oncologist visit, 75% of the patients were receiving active treatment (53% with hormonal therapy and 22% with chemotherapy). Only 25% were under continuous palliative care at this visit. Treatment was administered within the last month of life to 53% of the patients. The median duration from the last oncologist visit to death was 23 days (range: 0–408). The duration of this time interval was only associated with the performance status at the last visit (p < 0.05). Conclusions: Oncologists frequently delay the recognition of the need to discontinue systemic therapy. Patients with luminal HER2-negative ABC may be offered numerous effective lines of systemic treatment, complicating this decision further. Implementing clearer guidelines for end-of-life care for this group and providing proper training for healthcare providers is essential.

Real-world evidence for pembrolizumab in non-small cell lung cancer: a nationwide cohort study.

Based on favourable results from clinical trials, immune checkpoint inhibitors (ICI) have become the standard first line (1 L) systemic anticancer treatment (SACT) for advanced stage non-small cell lung cancer (NSCLC) without targetable mutations. We evaluate whether these results are generalizable to everyday clinical practice and compare overall survival (OS) of patients treated with ICI to a historical cohort of patients treated with chemotherapy and results from clinical trials. Our study comprised all advanced NSCLC patients initiating SACT in 2012-21 in Norway. Clinical characteristics and treatment information was retrieved from Norwegian Health Registries. Survival for all 8416 advanced NSCLC patients treated with SACT increased concurrently with the gradual implementation of ICIs. Median OS of patients treated with 1 L pembrolizumab after 2017 was better (mono-/combination therapy: 13.8/12.8 months) than for patients treated with chemotherapy before 2017 (8.0 months). Although median OS for patients treated with pembrolizumab was lower in clinical practice than clinical trials (Keynote-024/189: 26.3/22.0 months), the survival benefit relative to chemotherapy was similar. Our nationwide study demonstrated a survival benefit over conventional chemotherapy of a similar magnitude as observed in clinical trials and confirms the effectiveness of pembrolizumab in routine clinical practice.

Treatment Strategies' Impact on Progression-Free Survival According to RMST Function in Metastatic Colorectal Cancer Patients: A Retrospective Study from Romania.

Background: This retrospective study investigates the impact of various treatment strategies on progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC), a significant global health issue. Methods: We employed the restricted mean survival time (RMST) to evaluate how different treatments affect PFS over a defined period. The study included 225 patients with mCRC who were treated between 2015 and 2023 at the Oncology Department of Colțea Clinical Hospital in Bucharest. To assign KRAS status, mutation data from exons 2, 3, and 4 of the KRAS gene were required. Eligibility criteria included a confirmed histopathological diagnosis of colorectal adenocarcinoma, a valid RAS mutation test from a solid biopsy, radiological confirmation of stage IV disease by computed tomography, and at least one line of systemic treatment in the metastatic setting. Results: Our analysis revealed a small difference in PFS based on KRAS status, but this difference was not statistically significant. Neither sex nor the urban versus rural environment impacted PFS; however, the data indicated that educational level affected survival outcomes. Conclusions: Consistent with existing literature, our findings showed no survival benefit from locoregional treatments such as surgery of the primary tumor or curative radiotherapy at diagnosis. In contrast, resection of hepatic metastases was associated with improved survival outcomes.

Lenvatinib Plus Ifosfamide and Etoposide in Children and Young Adults With Relapsed Osteosarcoma

The combination of ifosfamide and etoposide (IE) is commonly used to treat relapsed or refractory osteosarcoma; however, second-line treatment recommendations vary across guidelines. To evaluate whether the addition of lenvatinib to IE (LEN-IE) improves outcomes in children and young adults with relapsed or refractory osteosarcoma. The OLIE phase II, open-label, randomized clinical trial was conducted globally across Europe, Asia and the Pacific, and North America. From March 22, 2020, through November 11, 2021, the trial enrolled patients aged 2 to 25 years with high-grade osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), and 1 to 2 prior lines of systemic treatment. The data analyses were performed between March 22, 2020 (first patient in) and June 22, 2022 (data cutoff for the primary analysis), and September 29, 2023 (end of study final database lock). The OLIE trial assessed the efficacy and safety of lenvatinib (14 mg/m2 taken orally once daily) combined with up to 5 cycles of ifosfamide (3000 mg/m2 intravenously) and etoposide (100 mg/m2 intravenously) on days 1 to 3 of each cycle vs IE alone at the same doses. Patients randomized to IE could cross over to receive lenvatinib upon disease progression by independent imaging review. The primary end point was progression-free survival (PFS) per RECIST 1.1 by independent imaging review. The Kaplan-Meier method was used to estimate the PFS distribution, with a prespecified 1-sided significance threshold of .025 by stratified log-rank test. Secondary end points included PFS rate at 4 months and overall survival. Adverse events were summarized using descriptive statistics. A total of 81 patients were enrolled (median [IQR] age, 15.0 [12.0-18.0] years; 46 males [56.8%]), with 40 in the LEN-IE arm and 41 in the IE arm. Median PFS was 6.5 months (95% CI, 5.7-8.2 months) for the LEN-IE arm and 5.5 months (95% CI, 2.9-6.5 months) for the IE arm (hazard ratio [HR], 0.54; 95% CI, 0.27-1.08; 1-sided P = .04). The rate of PFS at 4 months was 76.3% (95% CI, 59.3%-86.9%) in the LEN-IE arm and 66.0% (95% CI, 47.7%-79.2%) in the IE arm. Median overall survival was 11.9 months (95% CI, 10.1 months to not estimable) with LEN-IE and 17.4 months (95% CI, 14.2 months to not estimable) with IE (HR, 1.28; 95% CI, 0.60-2.70; 1-sided nominal P = .75). Grade 3 or higher treatment-related adverse events occurred in 35 of 39 patients (89.7%) in the LEN-IE arm and 31 of 39 patients (79.5%) in the IE arm. Although LEN-IE did not meet prespecified statistical significance for improved PFS vs IE, this study demonstrates the importance of international collaboration and randomized clinical trials in patients with relapsed or refractory osteosarcoma and may inform future trial design. ClinicalTrials.gov Identifier: NCT04154189.

Antibody-Drug Conjugates and Their Potential in the Treatment of Patients with Biliary Tract Cancer.

Background: Biliary tract cancers (BTCs) are aggressive in nature, often presenting asymptomatically until they are diagnosed at an advanced stage. Surgical resection or liver transplantation are potential curative options. However, a large proportion of patients present with incurable locally advanced or metastatic disease and most of these patients are only eligible for palliative chemotherapy or best supportive care. More recently, targeted therapies have proven beneficial in a molecularly selected subgroup of patients with cholangiocarcinoma who have progressed on previous lines of systemic treatment. However, only a minority of patients with BTCs whose tumours harbour specific molecular alterations can access these therapies. Methods: In relation to ADCs, studies regarding use of antibody-drug conjugates in cancer, particularly in BTCs, were searched in Embase (1974 to 2024) and Ovid MEDLINE(R) (1946 to 2024) to obtain relevant articles. Examples of current clinical trials utilising ADC treatment in BTCs were extracted from the ClinicalTrials.gov trial registry. Conclusions: Overall, this review has highlighted that ADCs have shown encouraging outcomes in cancer therapy, and this should lead to further research including in BTCs, where treatment options are often limited. The promising results observed with ADCs in various cancers underscore their potential as a transformative approach in oncology, warranting continued exploration and development and the need for education on the management of their specific toxicities. By addressing current challenges and optimising ADC design and application, future studies could potentially improve treatment outcomes for patients with BTCs and beyond, potentially in both early and advanced stage settings.

Optic pathway gliomas in children: Clinical characteristics, treatment, and outcome of 95 patients in a single center over a 31-year period. Can we avoid radiotherapy?

Optic pathway gliomas (OPG) are rare tumors in children. Lesion extent, visual functions, neurofibromatosis 1 (NF1), and age are factors that guide treatment. This study evaluates the clinical characteristics, treatment, and outcome of children and adolescents with OPG treated over a 31-year period in a single center. Ninety-five patients with OPG diagnosed between January 1990 and December 2021 were retrospectively evaluated. First-line chemotherapy regimen consisted of vincristine and carboplatinum for 1year. Radiotherapy was not used as first-line treatment and tried to be avoided in the ones who progressed after first-line treatment. Ninety-five children (44 male, 51 female) with a median age of 52 (1-216) months were evaluated. Sixty-three (66.3%) had NF1 and 10 (10,5%) diencephalic syndrome. The most common presenting symptoms were visual abnormalities and/or proptosis, nistagmus, and behavioral changes. Twenty-one (22.1%) patients with NF1 had stable disease throughout the follow-up period and received no treatment. Sixty-three of 74 patients received treatment at diagnosis and 11 due to progression during follow-up. Only one adolescent received radiotherapy at progression. Patients who progressed, received further line systemic treatment (vinblastine; bevacizumab; vincristine-cisplatinum-etoposide). Ten-year overall survival in all patients, in patients with NF1, and without NF1 were 97.2%, 98%, and 95.8% (p>.05), respectively; 10-year progression-free survival (PFS) in all patients, in patients with NF1, and without NF1 were 71.6%, 85.7%, and 54.2% (p=.001), respectively. In children with symptomatic/progressive OPG, chemotherapy consisting of vincristine-carboplatinum (VC) is effective. Radiotherapy may be avoided, especially in patients with NF1.

Golidocitinib: First Approval.

Golidocitinib (®) is an oral, potent, selective Janus kinase 1 (JAK1) inhibitor being developed by Dizal (Jiangsu) Pharmaceutical Co., Ltd for the treatment of cancer, including peripheral T cell lymphoma (PTCL). In June 2024, golidocitinib received conditional approval in China for the treatment of adult patients with relapsed or refractory (r/r) PTCL who have received at least one line of systemic treatment. This article summarizes the milestones in the development of golidocitinib leading to this first approval for the treatment of adults with PTCL.

Effect of polypharmacy and potentially inappropriate medications on physical functional decline among older adults with advanced cancer receiving systemic treatment.

Polypharmacy and potentially inappropriate medications (PIM) are common among older adults with advanced cancer, but their association with physical functional outcomes is understudied. This study aimed to estimate the risk of physical functional decline associated with medication measures in older adults with advanced cancer starting a new line of systemic treatment. This secondary analysis of GAP 70+ Trial (PI: Mohile) enrolled patients aged 70+ with advanced cancer, had ≥ 1 geriatric assessment domain impairment and planned to start a new antineoplastic regimen with a high risk of toxicity. Polypharmacy (concurrent use of ≥ 8 medications (meds)) was assessed before initiation of treatment. PIM were categorized using Screening Tool of Older Person's Prescriptions (STOPP) criteria and 2019 Beers criteria. Physical functional outcomes were assessed within 3months of treatment initiation: (1) Activity of Daily Living (ADL) decline: 1-point decrease in ADL score between baseline and 3months; (2) Instrumental ADL (IADL) decline: 1-point decrease in IADL score between baseline and 3months; (3) Short physical performance battery (SPPB) decline, defined as 1-point decrease on SPPB; (4) ≥ 1 falls within 3months of treatment. Separate multivariable, cluster-weighted Generalized Estimating Equations models adjusted for relevant covariates (e.g., age, baseline function/comorbidities). Among 616 participants, mean number of meds was 6 (range 0-24); 28% received ≥ 8 meds. Polypharmacy was associated with increased risk of ADL decline (adjusted risk ratio [aRR], 1.31; 95% CI, 1.00-1.71). Taking ≥ 1 PIM per STOPP was associated with increased risk of IADL decline (aRR, 1.21; 95% CI, 1.04-1.40) and falls (aRR, 1.93; 95% CI, 1.49-2.51). In a large cohort of vulnerable older adults with advanced cancer receiving systemic treatment, polypharmacy and PIM were independently associated with an increased risk of physical functional decline. This emphasizes the need to develop interventions to optimize medication use, intending to improve outcomes in these patients. ClinicalTrials.gov Identifier: NCT02054741. Registered 01-31-2014.

Lost opportunities: the underutilization of castrate-resistant prostate cancer treatment in real-world settings.

Various treatment regimens are now available for metastatic castrate-resistant prostate cancer (CRPC). This work evaluates the real-world prescription patterns of CRPC in a large tertiary care center and the factors influencing them. Health records of 330 patients with de novo metastatic hormone-sensitive prostate cancer (HSPC), treated and progressed to CRPC between 2016 and 2020, were reviewed from a prospective uro-oncological database. We studied their demographics, medical co-morbidities, treatment utilization patterns before and after progression to CRPC, and survival outcomes. The median age was 74 years [interquartile range (IQR), 67-80 years] at diagnosis of CRPC. At CRPC, beyond androgen deprivation therapy (ADT) monotherapy, 70.3% (n=232) of patients received at least one additional line, 21.5% (n=71) received two lines, and 5.5% (n=18) received three lines of systemic treatments. As first-line treatment, novel hormonal agents (NHAs) were the most prescribed at 57.6% (n=190). The likelihood of receiving treatment was associated with age <65 years [odds ratio (OR) 2.08, P=0.01, 95% confidence interval (CI): 1.22-3.57] and lower Charlson Comorbidity Index (CCI) score (OR: 2.62, P=0.04, 95% CI: 1.07-6.45), treatment intensification for HSPC (OR 2.45, P=0.04, 95% CI: 1.07-5.62) and primary physician being an oncologist (OR 1.59, P=0.04, 95% CI: 1.04-2.48). Patients who received additional treatment lines at CRPC had longer survival (median: 23 vs. 17 months, OR 1.72, P<0.01, 95% CI: 1.23-2.38). More than one in four patients do not receive any additional treatment line beyond ADT monotherapy and have worse survival outcomes. Health status, prescribing physician, and treatment at HSPC appear to affect prescription patterns at the CRPC stage.

Registry of Genetic Alterations of Taiwan Non-Small Cell Lung Cancer by Comprehensive Next-Generation Sequencing: A Real-World Cohort Study-Taiwan Cooperative Oncology Group T1521.

Tissue-based next-generation sequencing (NGS) analysis is highly recommended for patients with advanced/metastatic non-small cell lung cancer (NSCLC). We investigated a specific patient population with NSCLC that required tissue-based NGS analysis. We enrolled 500 patients with advanced/metastatic (1) epidermal growth factor receptor (EGFR) mutations or anaplastic large-cell lymphoma kinase (ALK) rearrangement-positive NSCLC who had failed at minimum one line of tyrosine kinase inhibitor (TKI) therapy, (2) EGFR-/ALK-negative nonsquamous, and (3) non- or light-smoker patients with squamous NSCLC who were treatment-naïve or had failed at maximum two lines of systemic treatment. These patients were divided into five cohorts. Comprehensive tissue-based NGS testing (ACTOnco+) was conducted. Cohort 1: EGFR TKI-pretreated EGFR-mutated population (50.0%, n = 250), cohort 2: ALK inhibitor-pretreated ALK-positive population (1.6%, n = 8), cohort 3: treatment-naïve EGFR-/ALK-negative population (28.2%, n = 141), cohort 4: pretreated EGFR-/ALK-negative population (16.8%, n = 84), and cohort 5: squamous cell carcinoma (3.4%, n = 17). In cohort 1, 11.2% (28/250) of the patients had MET amplification, 32.4% (81/250) had been treated with osimertinib, and EGFR C797S was detected in 6.2% (5/81) of these patients. In cohort 2, resistance ALK mutation was detected in 37.5% (3/8) of the patients. In cohorts 3 and 4, targetable genetic alterations, including EGFR mutation (13.3%), ERBB2 mutation (9.3%), MET exon 14 skipping (5.3%), KRAS G12C mutation (4.4%), ROS1 fusion (2.7%), RET fusion (1.8%), and BRAF V600E mutation (1.3%), were detected. In cohort 5, MET exon 14 skipping was detected in 29.4% (5/17) of the patients. This multicenter registration study investigated tissue-based NGS for a specific patient population with NSCLC in Taiwan.

Matching-Adjusted Indirect Comparison of Axicabtagene Ciloleucel vs Odronextamab for the Treatment of Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL) After 2 Prior Lines of Systemic Treatment

Matching-Adjusted Indirect Comparison of Axicabtagene Ciloleucel vs Odronextamab for the Treatment of Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL) After 2 Prior Lines of Systemic Treatment

ABCL-411 Matching-Adjusted Indirect Comparison of Axicabtagene Ciloleucel vs Odronextamab for the Treatment of Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL) After 2 Prior Lines of Systemic Treatment

ABCL-411 Matching-Adjusted Indirect Comparison of Axicabtagene Ciloleucel vs Odronextamab for the Treatment of Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL) After 2 Prior Lines of Systemic Treatment

Comparison of Clinical Characteristics and Outcomes of Patients with Breast Cancer and Liver Metastases Who Have or Have Not Undergone Radioembolization

The purpose of this study was to assess characteristics and outcomes of patients with breast cancer with liver metastasis who had and had not undergone radioembolization. Medical records of patients with breast cancer with liver metastases (4,332 patients who had not undergone radioembolization and 166 patients who had) seen between January 1, 2009, and October 31, 2021, were assessed. Propensity score matching was performed. Radioembolization patients were significantly younger (47.7 years [SD ± 10.1] vs 52.3 years [SD ± 12.5]; P < .001) and underwent more systemic treatment lines (8.6 [SD ± 4.1] vs 5.2 [SD ± 3.2]; P < .001). Median survival was longer in unmatched (67.1 vs 40.7 months; P = .001) and matched (67.1 vs 38.0 months, P = .001) cohorts. Radioembolization was associated with superior survival (P = .002). In conclusion, patients with breast cancer with liver metastases who underwent radioembolization were significantly younger and underwent more treatment lines. Radioembolization was associated with longer median survival.

Real-world use of immune checkpoint inhibitors in advanced or recurrent endometrial cancer

ObjectiveThe aim of this study was to describe real-world use of immune checkpoint inhibitors for women with advanced or recurrent endometrial cancer.MethodsAdult women with advanced or recurrent endometrial cancer who...

Contemporary Treatment Patterns and Oncological Outcomes of Metastatic Hormone-sensitive Prostate Cancer and First- to Sixth- line Metastatic Castration-resistant Prostate Cancer Patients

Background and objectiveWith approval of novel systemic therapies within the past decade for metastatic hormone-sensitive (mHSPC) and castration-resistant (mCRPC) prostate cancer, patients may receive several therapy lines. However, the use of these treatments is under an ongoing change. We investigated contemporary treatment trends and progression-free (PFS) and overall (OS) survival of different therapy lines. MethodsRelying on our institutional tertiary-care database, we identified mHSPC and mCRPC patients. The main outcome consisted of treatment changes (estimated annual percentage change [EAPC]) within the past decade, as well as PFS and OS for different mHSPC and mCRPC treatment lines. Key findings and limitationsIn 1098 metastatic patients, the median age was 70 yr with a median of two systemic therapy lines. For first-line mCRPC between 2013 and 2023, androgen deprivation monotherapy (ADT) monotherapy usage decreased significantly from 31% to 0% (EAPC −38.3%, p < 0.001), while the administration of chemotherapy increased from 16.7% to 33.3% (EAPC: +10.1%, p < 0.001). The PFS/OS rates of mHSPC patients was 21/67 mo, and those for first-, second-, third-, fourth-, fifth-, and sixth-line mCRPC patients were 11/47, eight of 30, seven of 24, six of 19, seven of 17, and seven of 13 mo, respectively. With an increased number of new combination therapy lines received, the median OS in mCRPC improved from 26 mo (one systemic treatment) to 52 mo (two or more lines of systemic treatment). Conclusions and clinical implicationsSignificant changes in treatment patterns could be observed for mHSPC and mCRPC patients within the past decade, and usage of ADT monotherapy has decreased rapidly in real-world practice. Moreover, PFS decreases significantly with every therapy line, and OS increases with the implementation of new therapies. Patient summaryImprovements in the real-world setting regarding the usage of combination therapies for metastatic hormone-sensitive and castration-resistant prostate cancer were made, which is reflected in contemporary survival outcomes.

Cisplatin Monotherapy as a Treatment Option for Patients with HER-2 Negative Breast Cancer Experiencing Hepatic Visceral Crisis or Impending Visceral Crisis.

Hepatic visceral crisis (VC), characterized by a rapid total bilirubin increase with disease progression, poses a life-threatening risk in advanced breast cancer (ABC). International consensus guidelines define VC and touch on impending VC (IVC). Limited data exist on systemic treatments for hepatic VC/IVC. This study explores the safety and efficacy of cisplatin monotherapy in patients with Human Epidermal Growth Factor Receptor 2- negative breast cancer (BC) and hepatic IVC/VC. In this retrospective single-center cohort study data of patients treated with cisplatin monotherapy (60-80mg/m2, every 3-4weeks) between 2016 and 2023 at a reference Cancer Centre in Southern Poland were analyzed. 33 female patients (24/33 hormonal-positive) with the mean age 53.84years were included. Participants progressed on median 2 prior palliative systemic treatment lines. In 10/23 patients hepatic VC and in 23/33 IVC (rapid, symptomatic liver progression; extensive liver involvement; alanine or aspartate aminotransferase > 2 × normal limit; significant increases in lactate dehydrogenase, alkaline phosphatase, or gamma-glutamyl transferase) were identified. Median progression-free survival was 1.87months and median overall survival 2.67months. 33% of the patients presented stable disease or partial response. Eight patients experienced adverse events grade ≥ 3: in five the dose of cisplatin was reduced; two stopped the treatment. Due to the hepatotoxicity of BC-active drugs, specific recommendations for systemic treatment are scarce. Our study explored cisplatin's potential use, finding it to be a viable option in patients with performance status 0 or 1 experiencing hepatic IVC/VC, irrespective of liver function parameters and other factors.

Oncology triage utilization among patients with gynecologic cancers.

e13551 Background: Emergency department (ED) utilization among patients with cancer is associated with significant burden including financial costs, resource allocation, and the patients’ experience of time spent seeking care. Moreover, studies have demonstrated that cancer patients are commonly seen in the ED for issues that do not require inpatient management and could be managed in outpatient settings. Oncology-specific urgent care centers have previously been demonstrated to decrease ED utilization and may be a potential remedy to the time toxicity experienced by patients receiving cancer care. This retrospective review aims to identify patient characteristics, resource utilization, and disposition of patients with gynecologic cancers who present to an advanced practice provider-driven, cancer-specific urgent care center (“oncology triage”) embedded in a tertiary academic center in an urban setting. Methods: We conducted a retrospective review of all gynecologic oncology patients who presented to oncology triage for any indication from May 16, 2022 to May 16, 2023.We describe the patient population utilizing oncology triage, the services provided, and time-based outcomes to assess efficiency, including time from presentation until being roomed, time to admission, and time to undergoing imaging. Results: 104 patients with gynecologic cancer were seen in oncology triage during the study period. Most patients had ovarian (43.2%) and endometrial (42.3%) cancers, and fewer had cervical cancer (10.6%). 60.6% were on their first or second line of systemic treatment. Insurance coverage included 17.3% Medicaid, 33.7% Medicare, 46.2% private, and 2.9% were uninsured. Pain (40.4%) and nausea (31.7%) were the most common chief complaints. 25.0% and 23.1% of patients had an X-ray or CT scan ordered, respectively. Intravenous fluids (69.2%) and supportive medications (e.g., antiemetics, opiates; 51.9%) were the most frequent therapeutics administered. 19% were evaluated and reassured by provider without needing additional treatment. 35.5% of all patients seen were admitted. On average, patients were roomed and seen by the care team in 9 minutes. The average time from presentation to oncology triage to hospital admission was 5 hours and 1 minute. Conclusions: In a single-center study of oncology triage utilization among patients with a mix of gynecologic cancers, we found that an oncology-specific urgent care center evaluates and manages common acute cancer-related complaints in a timely fashion. Oncology triage offers a high-acuity patient population an alternative to the ED that is much more time efficient when compared to historic ED wait times. Our findings support oncology-specific triage as a valid model of care for a subset of common acute gynecologic cancer-related problems and highlight its potential to improve patients’ experience of their cancer care.

Outcomes of personalized therapy guided by Exacta encyclopedic tumor analysis for women with broadly refractory advanced breast cancer.

e13124 Background: Following the failure of three lines of systemic treatments in breast cancers, Standard of Care guidelines typically recommend palliative care or participation in clinical trials for such patients. Breast cancer remains a global health threat, impacting lives worldwide. For refractory patients, the outlook is grim, with limited treatment options post multiple failures. Dismal outcomes underscore the urgency for innovative approaches, as traditional interventions often fall short. Methods: The Resilient trial was a Phase-II, single-arm, open-label clinical trial. Its primary objective was to assess the effectiveness of Exacta ETA-guided treatments across a spectrum of solid organ cancers in advanced refractory cancer patients. Exacta Encyclopedic Tumor Analysis (ETA) comprising the interrogation of gene alterations, gene expression, immunohistochemistry (IHC), and in vitro chemoresistance profiling (CRP) of viable tumor cells was performed on freshly obtained tumor tissue from 21 breast cancer patients with broadly refractory advanced breast cancers who had failed multiple lines of treatment. Six (29%) patients had metastasis to the brain, 11 (52%) patients had metastasis to the liver, 9 (43%) patients had metastasis to the lungs, and 15 (71%) patients had skeletal metastasis. The findings obtained through Exacta ETA were integrated to formulate patient-specific therapy recommendations. Personalized treatment plans were devised, and organ- and label-agnostic treatment regimens were administered to each patient. Patients were monitored to ascertain Overall Survival (OS). Results: Median overall survival (OS) was not reached at the time of analysis. By considering the OS values censored at the interim (most recent follow-up), the median OS in the entire cohort (n = 21) was 11.5 months (95% CI 4.5 to 16.9). The median OS was 11.4 months (95% CI 4.0 to 15.1) among patients with brain metastases, 14.5 months (95% CI 2.6 to 22.8) among patients with liver metastases, 11.9 months (95% CI 3.7 to 22.3) among patients with pulmonary metastases and 11.4 months (95% CI 3.7 to 22.3) among patients with skeletal metastases, respectively. No grade IV adverse events or treatment-related deaths were reported in the cohort. Conclusions: Exacta Encyclopedic Tumor Analysis (ETA) guided treatments provide a viable and meaningful treatment option for patients with advanced refractory breast cancers with metastatic deposits. The observed high OS in this heavily pretreated population underscores the value of multi-analyte guided of Exacta ETA as a valuable approach to managing these challenging clinical cases. Clinical trial information: CTRI/2018/02/011808.

Patterns of progression in oligometastatic hormone receptor positive breast cancer after first-line systemic treatment at the metastatic stage.

e13054 Background: In recent years, thanks to large, consecutive and retrospective series, knowledge of oligometastatic breast cancer (OMBC) has improved. However, the underlying pathophysiological mechanisms and patterns of progression of OMBC remain largely unknown. The aim of this study is to determine whether the limited capacity of OMBC to metastasize persisted in patients receiving first-line systemic treatment at the OMBC stage. To obtain a biologically homogeneous cohort, the analysis focused on hormone receptor positive (HR+) OMBC. Methods: We retrospectively reviewed all patients consecutively diagnosed and treated from 2012 to 2020 at our institution for synchronous and metachronous HR+ OMBC. Included were HR+ MBC patients with up to five metastases at diagnosis with no other criteria. Clinical and biological characteristics at diagnosis of first metastases, types of treatment (local ablative treatment of all sites (LAT) vs palliative treatment), outcomes and patterns of progression after a first line systemic treatment at the oligometastatic stage were recorded. Progression-free survival (PFS) and overall survival (OS) rates with a 95% confidence interval were estimated using the Kaplan Meier method. Results: Out of 1,686 patients treated for MBC at our institution between 2012 and 2020, 11.0% (186/1,686) met inclusion criteria. Among these 186 HR+ OMBC patients, 62.2% had SBR grade I/II HR+, and 19.3% had HER2+ OMBC. 93.5% patients had only one organ invaded, and 88.2% patients had one to three metastases at diagnosis. 66.7% had bone metastases, 60.2% had bone-only metastases, 18.3% had visceral (lung or liver) metastases, 14.5% had lymph node metastases and 6.5% had brain metastases. 35.5% of patients were treated with a curative intent including systemic treatment plus LAT. After a median follow-up of 73.4 months (95%CI= [69.3-76.8]), median PFS and OS were respectively 31.6 months (95%CI= [23.7-37.4]) and 90.9 months (95%CI= [70.0-109.9]). Five years PFS and OS were respectively 32.6 % (95%CI= [25.5-39.9]) and 66.3% (95%CI= [58.4-73.1]). During this period, 64.0% (119/186) of HR+ OMBC patients presented disease progression. Among the latter, 74.1% showed spread with no more than five metastases (oligoprogression), and 82.6% in only one organ. 27.7% (33/119) of patients were able to benefit from LAT. Conclusions: HR+ OMBC incidence is 11%. Among patients with progressive HR+ OMBC following first-line systemic treatment at the oligometastatic stage, a large majority presented oligoprogression and a substantial proportion were able to be treated by local ablative therapy with a curative intent at the time of this progression. The limited capacity of HR+ OMBC to metastasize thus persisted after a first-line systemic treatment. This could be an argument in favor of physiopathological mechanisms specific to oligometastatic disease.

A retrospective study of tislelizumab combined with bevacizumab, pemetrexed, and carboplatin in driver-gene mutated advanced non-squamous non-small cell lung cancer after tyrosine kinase inhibitors failure.

e20620 Background: Overcoming resistance to tumor targeted therapies is a major challenge in the management of driver-gene mutated non-small cell lung cancer (NSCLC). Recent clinical trials suggested that the combination approach of immunotherapy, bevacizumab and platinum-based chemotherapy was effective for driver-gene mutated NSCLC after tyrosine kinase inhibitors (TKIs) failure. Our retrospective study was aimed to examine the efficacy and safety of tislelizumab (TIS) combined with bevacizumab plus chemotherapy for advanced driver-gene mutated non-squamous NSCLC (nsq NSCLC) who had failed to TKIs therapies. Methods: We retrospectively collected medical records of driver-gene mutations advanced nsq NSCLC who had failed to TKIs therapies in the Affiliated Hospital of Zunyi Medical University and Second Affiliated Hospital of Zunyi Medical University from January 2021 to December 2023. The participants were sorted into two groups. Pts in TBCP group received TIS combined with bevacizumab, carboplatin and pemetrexed (BCP) for six cycles, followed by TIS with pemetrexed as maintenance therapy. Pts in BCP group received BCP regimen for six cycles, followed by pemetrexed as maintenance therapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: A total of 12 pts were enrolled (6 pts in TBCP group and 6 pts in BCP group). In TBCP group, there was one patient with EGFR exon 19del, KRAS, BRAF V600 mutation and RET fusion, respectively. 2 pts harbored EGFR exon 21 L858R mutations. In BCP group, 4 pts harbored EGFR exon 19del, 1 patient with exon 21 L858R, and 1 patinet with BRAF V600 mutation. All pts were failed to previous TKI therapy. 3 pts (50%) had progression after two systemic treatment lines in ABCP group. 4 pts(66.7%) had progressive disease after at least two systemic regimen. As of 6 February 2024 (median follow-up, 18.6 months), significantly longer PFS was observed in TBCP group compared with BCP group (HR = 0.269 [95% CI: 0.068-1.065], p = 0.0080). Median PFS was 14.20 months (95% CI: 0.5010-5.379) and 8.65 months (95% CI: 0.1859-1.996) in TBCP group and BCP group, respectively. A higher ORR assessed was observed with TBCP group (66.7%) compared with BCP group (33.3%). The DCR were both 100% in two groups. Median OS was not reached. Grade 3-4 TRAEs occurred in 1 and 2 pts in TBCP group and BCP group, respectively. Conclusions: TIS combined with bevacizumab, carboplatin and pemetrexed has shown a promising anti-tumor efficacy with manageable safety profile for TKI failure driver-gene mutations advanced nsq NSCLC. However, these findings still need to be further confirmed by prospective clinical trials with larger sample sizes.