Majority Of Pts Research Articles

P104 MEDICAL TREATMENT IN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION HOSPITALIZED AT RESEARCH INSTITUTE OF CARDIOLOGY DURING 1 YEAR (FROM SEPTEMBER 2022 TO SEPTEMBER 2023)

Objective: Patients with heart failure remain most challenging group of patients with cardiovascular diseases. Hospital period of these patients is important period of their life. Therefore evaluation of the level of in- hospital care and treatment options represents valuable information. Design and method: 477 patients (pts), 13% female,87% male with HFrEF hospitalized at Research Institute of Cardiology during 1 year (September 2022 – September 2023) represented study population. Consecutive patients’ data was extracted from the archive of Institute and evaluated. Results: Majority of pts had NYHA III-IV and mean ejection fraction (EF) of 35% (26-43%).Atrial fibrillation (AF) observed in 17,8% out of 477 pts. Myocardial infarction (MI) in anamnesis was in 82%. Systolic Blood Pressure (SBP) – mean 137 mm.Hg(min 80-max 240),Diastolic Blood Pressure(DBP) – mean 84 mm.Hg(min 50 – max 140).Arterial Hypertension(AH) had 61,4%. Type 2 Diabetes (T2D) – 51%.Chronic Kidney Disease had 22,9%.Pulmonary artery hypertension – 33%.Hb<12 g/l had 22,4%.ACE inhibitors or ARB mainly in form of fix combination with thiazide diuretics received 34% out of 477pts. ARNI were used in 27,7% of pts.B-blockers-55%. MRA – 89%. SGLT2 inh – 17,4%.Loop diuretics-86,2%.Digoxin-28,8%.Amiodarone – 22,9%.Ivabradine – 6%. Lab, tests: К+ mean 4,4 (2,9-6,2). Na+, mean 140,4 (133- 155). NT-proBNP, mean 2246.39 pg/ml (10.0-30000.0). Conclusion: In significant number of patients with HFrEF hospitalized to Research Institute of Cardiology during the period from September 2022- September 2023 medical therapy was almost adequately adherent to modern international guidelines on management of heart failure. In some cases’ limitations for indication because of low blood pressure, low eGFR and high serum kalium level took place.

Development and implementation of a digital health intervention (DHI) electronic patient-reported outcome measure (ePROM) platform to monitor patients with cancer.

163 Background: Cancer is heterogeneous diseases associated with a significant burden of symptoms and treatment-related adverse events. Digital Health Interventions (DHIs) emerge as promising tools for active/continuous monitoring of patients (pts). Evidence suggests that DHIs may enhance healthcare delivery and improve clinical outcomes by facilitating symptom detection and enabling more effective real-time informed decisions. We aim to develop and implement an electronic Patient-reported Outcome Measure (ePROM) platform to monitor pts undergoing cancer treatment. Methods: We developed ThummiOnco, a DHI ePROM platform designed for monitoring of pts during cancer treatment. It allows pts to report their symptoms (reported and graded according to the CTCAE), quality-of-life (QoL) (EORTC EQ-5D questionnaire), emotional state, treatment adherence (Morisky-Green questionnaire), Emergency Room (ER) visits and hospitalizations through a mobile application. Upon registration, pts consent to share their data with their medical team and provide essential demographic information such as age, sex, cancer type, and treatment regimen. A medical algorithm analyzes the collected data to generate instant personalized recommendations and guidance, including indicating the need of seeking emergency care in the case of serious high-grade or worrisome complaints. Patients also have the option to engage in real-time conversations with the medical team through an online chat feature. Treating physicians and the medical team can continuously access pts data real-time, through an online dashboard, enabling them to visualize information and statistics, address symptom alerts, and make informed management decisions. ThummiOnco is available at no cost to pts at htt ps://thummi.global . Results: Between August 2021 and March 2024, ThummiOnco monitored 925 pts across 7 institutions in Brazil, encompassing both private and public health systems. The majority of pts (72%) were female, with 28% being male. The most frequently monitored cancer types were Breast Cancer (39%), Lung Cancer (7%) and Colon Cancer (6%). During this period, a total of 71.373 interactions were recorded, including 36.175 (51%) chat messages, 21.644 (30%) symptom reports, 10.597 (15%) emotional state reflections, 2.819 (4%) QoL assessments, and 138 (0.2%) ER registries. A total of 23 different symptoms were reported, with the most frequent being: fatigue (16%), joint pain (8%), and nausea (7%). 13.187 (61%) grade 1, 6.545 (30%) grade 2, and 1.912 (9%) grade 3 symptoms were registered. In total, the medical algorithm generated 1.921 recommendations for seeking emergency care. Conclusions: ThummiOnco's capacity to detect a wide range of symptoms and enable real-time informed decisions underscores its potential to enhance patient outcomes and healthcare service delivery.

The immunological milieu of oropharyngeal squamous cell carcinoma (OPC) according to HPV and smoking status and its influence on prognosis.

3147 Background: OPC exhibits distinct epidemiological, genetic, and clinical characteristics, significantly influenced by the presence of HPV. Despite multidisciplinary therapy, approximately 40% of OPC patients (pts) experience recurrence, and those who achieve cure often endure late and morbid sequelae of treatment. In this study, we comprehensively explored the composition and functional status of the tumor immune microenvironment (TIME) in a cohort of OPC pts treated with curative intent and investigated TIME differences based on HPV infection, smoking status, and clinical outcomes. Methods: Two tissue microarrays with baseline OPC tissues were stained with a previously validated panel containing 33 metal-tagged markers. Imaging mass cytometry was performed with the Fluidigm Helios CyTOF instrument, and analysis performed with Visiopharm software. HPV status was determined by p16 IHC and/or DNA testing. Comparison of cell types and markers densities among subgroups (HPV positive vs negative) were analyzed with Wilcoxon signed-rank test and its association with clinical outcomes (recurrence vs no-recurrence) with log-rank and Cox Proportional Hazards. Multiple comparisons were corrected by Benjamini Hochberg procedure. Results: A total of 99 samples from 61 pts from a single institution were included in this study. The majority of pts were male (N=47, 77%) and heavy smokers (N=55, 90%); 72% were HPV-negative. The median age was 61 years (range, 39 – 87 years), and 52% of cases were diagnosed with stages III-IVB (AJCC 8th edition). Most pts (57%) was treated with surgery (±RT). Thirty-three pts (54%) experienced recurrent disease. Smoking, stage III-IVB, and HPV-negative tumors were associated with higher recurrence rates (p <0.01). Regarding the OPC TIME, the most prevalent cell populations in the stroma were fibroblasts (22%), followed by T-cells (17%) and endothelial cells (10%). The stroma of HPV+ tumors exhibited higher densities of memory T cells (FDR < 0.01), B cells (FDR = 0.02), and T cells (FDR = 0.02) compared to HPV negative counterparts, which displayed an increased density of neutrophils (FDR = 0.04). The density of cancer stem cells was directly associated with smoking history (FDR<0.001), and an increased density of intra-tumoral B-cells was found in non-smokers (FDR=0.01). Higher intra-tumoral neutrophil density was linked to recurrent disease (FDR < 0.001). Conversely, higher densities of memory CD8+ T cells and non-M2 macrophages in the TIME were associated with a lower chance of recurrence (FDR < 0.1). Conclusions: The intricate analysis of the OPC TIME revealed significant differences according to HPV and smoking status and highlighted the prognostic role of neutrophils, memory CD8+ T cells, and non-M2 macrophages. These findings may guide the development of personalized therapeutic strategies for OPC.

Safety and efficacy of first-in-class CXCR1/2 inhibitor SX-682 in combination with pembrolizumab (pem) in patients (pts) with metastatic melanoma (mMEL) with disease progression on anti–PD-1 therapy.

9508 Background: Outcomes for pts with mMEL remain sobering despite access to available immunotherapies as the majority of pts are resistant or become refractory to checkpoint blockade with no approved treatments. CXCR1 and CXCR2 (CXCR1/2) signaling mediate myeloid immunosuppression and MEL growth, inversely correlating with anti-PD-1 response and pt survival. SX-682 is an oral allosteric inhibitor of CXCR1/2. As a single agent, SX-682 increases tumor CD8+ T cell infiltration and inhibits tumor growth in mouse MEL. Methods: This phase 1 dose-escalation with expansion trial (NCT03161431) evaluated pem and escalating doses of SX-682 (25 - 400 mg orally BID) in pts with mMEL in a 21-day cycle. Pts must have had progressive disease (PD) on prior anti-PD-1. Mucosal MEL and asymptomatic brain metastases were allowed. Escalation cohorts had a 21-day SX-682 monotherapy (MONO) run-in. Response assessment by RECIST 1.1 was every 2 cycles during combination (COMBO) treatment. Primary endpoint was safety: adverse events (AEs), dose-limiting toxicity (DLT) and maximally-tolerated dose (MTD). Secondary endpoints included objective response rate (ORR; complete [CR] + partial [PR] response), disease control rate (DCR; CR + PR + stable disease [SD]) and overall survival (OS). Results: As of October 2023, 51 pts were enrolled and treated; median age of 65 (range 24-91), 55% male, 61% elevated LDH, 39% BRAF mutated. All pts received prior anti-PD-1, 37 (73%) received combined anti-PD-1 and anti-CTLA-4, and 23 (45%) had ≥ 3 prior therapies. Steady-state blood SX-682 was dose-proportional. No MONO DLT or MTD was identified. The 200 mg dose cohort was expanded in COMBO based on safety and pharmacodynamics: mg BID dose (n) = 25 (3), 50 (3), 100 (6), 150 (8), 200 (31). Any grade and grade 3/4 treatment-related AEs (TRAEs) occurred in 75% and 43%, respectively, and discontinuation (DC) due to TRAEs in 20% (when uncomplicated neutropenia, a permitted effect from CXCR2 inhibition on bone-marrow trafficking, was excluded there were 25% grade 3/4 TRAEs and 12% DC [rash, transaminitis]). There was no infectious signal. At the 200 mg dose, the ORR was 21% in 19 evaluable pts (4 PR + 0 CR) and the DCR was 63% (8 SD + 4 PR). DCR significantly depended on SX-682 dose ( P vs. ≤100 mg): 0% (0/9) at ≤100 mg, 50% (3/6) at 150 mg ( P = 0.0440) and 63% (12/19) at 200 mg ( P = 0.0028). All 15 pts with disease control had progressed on anti-PD-1 and anti-CTLA-4. Median OS was longer in pts in the 200 mg cohort (14.7 months; 95% CI, 10.5 – NR [not reached], n = 31) than in pts treated with ≤100 mg SX-682 (7.4 months; 95% CI, 5.0 – NR; n = 10). Conclusions: SX-682 combined with pem had a tolerable safety profile and activity reflected by objective responses and clinically meaningful disease control in heavily pretreated mMEL pts with progression on anti-PD-1 and anti–CTLA-4. Clinical trial information: NCT03161431 .

A real-world assessment of the treatment-related symptoms and associated burden among patients with lung cancer receiving chemotherapy.

e23159 Background: For patients (pts) with metastatic non-small cell lung cancer (NSCLC), treatment with chemotherapy has shown improved survival, symptom control, and increased quality of life. In clinical trials, the adverse event profile associated with these treatments has been identified. Less explored is the real-world experience of treatment-related symptoms and treatment burden. The objective of this study is to evaluate treatment-related symptoms and treatment burden among chemotherapy-treated NSCLC pts through an electronic remote symptom monitoring system. Methods: Pts diagnosed with NSCLC who received chemotherapy at U.S. academic cancer centers were enrolled in the Carevive’s Patient Reported Outcomes Mobile Platform (Carevive PROmpt®) from September 2020 - June 2023. 174 pts were enrolled. Weekly PRO-CTCAE-derived surveys assessed severity, frequency, and interference for 16 symptoms: anxiety, constipation, cough, decreased appetite, diarrhea, fatigue, general pain, insomnia, mouth/throat sores, muscle pain, nausea, numbness and tingling, rash, sadness, shortness of breath, and vomiting. The GP5 assessed weekly overall side effect treatment bother. Results: The mean age of NSCLC pts was 67.3 (SD = 9.2) years, with 51% female, and 12% African American. The majority of pts, 126 (72%), were enrolled at or within 1 month of the start of treatment. Ninety-one (52%) received chemotherapy and 83 (48%) received chemotherapy in combination. At enrollment, cough, fatigue, and shortness of breath was reported by > 40% of pts receiving chemotherapy, with constipation, decreased appetite, general pain, and numbness/tingling occurring in > 20% of pts. Over 40% of pts reported being at least “somewhat” bothered by the side effects of treatment. Pts with decreased appetite, nausea, and numbness/tingling were more likely to rate symptoms as “somewhat” or “very much” bothersome. No differences were noted for those with combination regimens. Conclusions: For real-world chemotherapy pts, the most frequent symptoms at enrollment were cough, fatigue, shortness of breath, decreased appetite, general pain, and numbness/tingling. Patients with decreased appetite and numbness/tingling were more likely to note higher treatment bother. Results show the feasibility of assessing symptom burden and corresponding patient bother in a real-world NSCLC population, which will have increasing importance increasing use of new treatment modalities with and without cytotoxic chemotherapy. [Table: see text]

Safety of pressurized intraperitoneal aerosolized chemotherapy (PIPAC) in patients (pts) with biliary tract cancer with peritoneal metastases.

TPS4186 Background: Biliary tract cancers are rare with the majority of pts diagnosed with metastatic disease at initial presentation. Up to 20% of pts will have peritoneal metastases, resulting in symptoms of ascites, abdominal pain, and potential bowel obstruction. Despite advances in standard of care systemic treatments such as combination gemcitabine, cisplatin, and durvalumab (gem/cis/durva), penetration to peritoneal metastases may be poor. While addition of nab-paclitaxel to gem/cis increased objective response in a phase 2 study (1), SWOG 1815 did not demonstrate a significant improvement in survival with the triplet combination compared to gem/cis (2), possibly due to added toxicity. PIPAC directly delivers treatment to the peritoneal space, which could potentially reduce toxicity and improve efficacy. We aim to investigate the safety of PIPAC nab-paclitaxel plus systemic gem/cis/durva in biliary tract cancer pts with peritoneal metastases. Methods: This is an investigator-initiated, non-randomized phase 1 trial enrolling up to 12 evaluable pts using a modified phase 1 queue 3+3 design. Eligible pts must have treatment-naïve histologically or cytologically confirmed intra/extra-hepatic cholangiocarcinoma or gallbladder cancer with documented metastatic disease and visible peritoneal disease on imaging or laparoscopy. Gem/cis (800/25 mg/m2) will be administered on Days 1 and 8 of 3-week cycles; durva (1500 mg) will be administered on Day 1. Pts will receive PIPAC nab-paclitaxel (90 mg/m2) on Day 3 of Cycles 1, 3, and 5. If dose-limiting toxicities (DLTs) occur, nab-paclitaxel may be reduced to 70 mg/m2; the DLT window for each pt is 42 days after the first PIPAC. After eight 3-week cycles, durva (1500 mg) will be continued on Day 1 of 4-week cycles until disease progression or unacceptable toxicity. The primary endpoint is treatment-related adverse events (AEs) graded by NCI Common Terminology Criteria for Adverse Events version (v) 5.0. AEs will be monitored during treatment and for 4 weeks after the last dose of treatment with any agent. Secondary endpoints include objective response per Response Evaluation Criteria in Solid Tumors v1.1, peritoneal regression grading score at each PIPAC, peritoneal carcinomatosis index at time of laparoscopy, post-operative surgical complications, progression-free/overall survival, PIPAC technical failure rate, EQ-5D-5L and MD Anderson Symptom Inventory responses before/during treatment, and number of daily steps taken before/during treatment. Exploratory endpoints include characterization of sub-clonal tumor evolution/tumor microenvironment changes and PIPAC nab-paclitaxel pharmacokinetics/pharmacodynamics. Enrollment began 6/2023 and is ongoing. 1. Shroff et al, JAMA Oncol 2019. 2. Shroff et al, JCO 2023 LBA490. Clinical trial information: NCT05285358 .

A phase I/II study of KD6001, a novel fully human anti-CTLA4 IgG1 monoclonal antibody, in combination with toripalimab in patients with advanced melanoma.

9527 Background: Anti-CTLA4 and anti-PD-1 immunotherapies have changed the treatment landscape of patients (pts) with advanced or metastatic melanoma. However, there is still a need to develop an anti-CTLA-4 antibody with further improved safety and efficacy profile. KD6001, a novel fully human anti-CTLA4 IgG1 monoclonal antibody that exhibits immunomodulatory effects, enhances T-cell-mediated anti-tumor immune response, and shows preliminary anti-tumor activity as monotherapy in a FIH phase I trial in pts with advanced solid tumors. Here we report a new study result of KD6001 in combination with toripalimab, an anti-PD-1 monoclonal antibody, in pts with advanced melanoma (KD6001CT02). Methods: KD6001CT02 is a phase I/II study conducted in advanced melanoma. This study consists of dose escalation and dose expansion phases. The primary objective is to evaluate the safety and tolerability of KD6001 in combination with toripalimab and determine the MTD/RP2D. The secondary objectives are to measure antitumor activity, immunogenicity, and pharmacokinetics (PK). Results: As of 15 Dec 2023, 29 pts with melanoma were enrolled (dose escalation n=6 and dose expansion n=23), including 9 (31.0%) acral, 9 (31.0%) nonacral cutaneous, 8 (27.6%) mucosal, and 3 (10.3%) unknown primary subtypes. 18 of them had no brain metastases. The median age was 56 yrs (range 41-78 yrs). The majority of pts previously received anti-PD-1/L1 therapy (16/29, 55.2%) and 27.6% of them received ≥3 lines of therapy. No dose-limiting toxicity or ≥Gr 3 adverse events (AEs) were reported in the dose escalation phase. The study did not reach MTD. 26 (89.7%) pts had treatment-related adverse events (TRAEs), with ≥Gr 3 TRAEs occurring in 3 (10.3%) pts and were well manageable. All other TRAEs were Gr 1 or 2. There were no death events due to TRAEs. No novel safety signals were seen other than the previously reported safety profile of treatment with a combined inhibition of CTLA-4 and PD-1. At data cutoff, among 13 efficacy-evaluable pts without brain metastases, the unconfirmed and confirmed objective response rates (ORR) were 38.5% and 23.1%, respectively. The disease control rate (DCR) was 76.9%. Among 3 pts with confirmed partial response (PR) , 2 pts were mucosal melanoma and 1 patient was nonacral cutaneous melanoma. Among 7 pts who received KD6001 as the ≥2 line treatment and all failed anti-PD-1/L1 therapy, the unconfirmed and confirmed ORR were 57.1% and 42.9%, respectively. DCR was 85.7%. The median PFS and OS were not reached. Conclusions: KD6001 in combination with toripalimab for treatment of advanced melanoma was safe, well-tolerated and showed anti-tumor activity in pts with advanced melanoma. Preliminary analysis indicates that KD6001 combined with toripalimab is efficacious in pts who have progressed after previous anti-PD-1/L1 therapy and in pts with mucosal melanoma. Clinical trial information: NCT05723432 .

Nivolumab combined with high dose multisite radiotherapy in previously untreated advanced melanoma (NIRVANA): A non-randomised, open-label, multicenter, phase 2 trial.

e21505 Background: Outcome of advanced melanoma remains poor for the majority of patients (pts) and new treatment strategies are needed. Preclinical and clinical data suggest a potential increase of the immunotherapy efficacy when combined with hypofractionated multisite radiotherapy (HMR). Objective: To assess the impact of HMR combined with nivolumab in advanced melanoma. Methods: This is a non-randomised, open-label, multicentre phase 2 trial(NCT02799901). Pts must have locally advanced or metastatic melanoma (AJCC7), previously untreated. Pts with mucosal or uveal melanoma, those with brain metastasis and LDH ≥ 1.5 the upper limit were not included. Pts received (until progression or unacceptable toxicity) nivolumab (fixed dose 240 mg/15 days) plus radiotherapy (day 15) delivered 3 x 6 Gy every second day, at every metastatic organ, if feasible.At progression, second irradiation was authorized while pursuing nivolumab (rechallenging strategy).The primary endpoint was 1-year overall survival (OS) (hypothetic improvement of 1-year OS from 71%1). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Subgroups and multivariate analyses were performed. Results: A total of 64 pts were included, from 03/2017 to 07/2019. Median follow-up was 23.5 months [IQR 2.3-43.8]. Median age was 64 years [35-95], majority of pts were male (67%), had an ECOG-PS 0 (75%), a stage IV-M1C disease (47%) and were BRAF-wild-type (67%).] The 1-year OS and PFS rates were 79% and 56% respectively (p = 0.12 and p = 0.0.3 in comparison with the 1-year OS and PFS of 71% and 43% of Robert et al’study1). 39 pts were irradiated at 1 target, 25 at ≥2 targets (total of 92 tumor targets). The 2-years OS rates were 83% and 52% for pts who were irradiated on several sites and one site respectively (p = 0.03). The ORR in the whole cohort was 53% [95% CI, 40.23; 65.72], 33% [95% CI, 14.59; 56 .97] and 62% [95% CI, 45.64; 76.43] in BRAF mutated and BRAF-wild type respectively. Among BRAF status, gender, PS, stage, age, LDH level and number of irradiated sites (1 vs ≥ 1), the independent prognostic factors for OS in multivariate analysis were number of irradiated sites (HR = 0.26, p = 0.03) and ECOG-PS (HR = 6.2, p = 0.001). Rechallenging was performed in 11 pts, among them; 3 were progression-free at last follow-up, 10 were reirradiated once and 1 was reirradiated 3 times. ICI was stopped due to toxicities for 6 pts. Drug-related adverse events of grade 3-4 occurred in 8.3% of the patients (no grade 5). Conclusions: Combined nivolumab and HMR did not improve significantly OS compare to nivolumab alone but improve significantly PFS1. However, this strategy has an acceptable safety and could be a treatment option for some patients. Multisite irradation and rechallenging strategies deserve to be considered. 1 Robert et al, J Clin Oncol 2020. Clinical trial information: NCT02799901 .

The impact of self-reported social determinants of health (SDOH) on patient engagement and symptom burden across a remote patient monitoring (RPM) pathway in 42 European hospitals.

1506 Background: SDOH are a significant driver of cancer care disparities impacting access to care, adherence to treatment plans, treatment-related toxicities and quality of life (QoL) across the cancer care continuum. RPM based on electronic patient-reported outcomes (ePROs) is a powerful tool to facilitate communication between pts and providers, thereby improving symptom management, QoL and disease outcomes. Equitable participation in RPM pathways must be ensured to avoid increase existing disparities. In this study we report the prevalence of unfavorable SDOH and their impact on engagement with RPM and symptom burden in an RPM pathway deployed in routine care across 42 hospitals in FR and BE. Methods: Patient-level SDOH data provided by consented pts enrolled in the RPM pathway between 08-2023 and 12-2023 was used. Single-item questions were dichotomized from validated ePROs covering educational level, health literacy (3 subdomains health status, treatment and disease understanding), digital literacy, employment status, financial and food security, caregiver support, and access to care. SDOH profiles were defined as unfavorable (impairment at moderate/elevated level) vs. favorable (absence or impairment at a low level). RPM engagement and symptom burden were defined respectively as weekly ePRO reporting and number of alerts due to severe or worsening symptoms. Multivariable backward stepwise regression models (including age, gender, stage, health behaviors) assessed associations between SDOH profile and RPM engagement and symptom burden. Results: 896 (40%) pts provided SDOH data, of which 622 (69%) females with median age of 60 (P25-75 50-70). Most common primary tumor were breast (436, 49%) and gastrointestinal (171, 19%), 488 (55%) were non-metastatic. 653 (73%) pts reported at least 1 unfavorable SDOH, specifically: 199 (22.2%) on educational level, 134 (15.0%) on health status understanding, 27 (3.0%) on treatment understanding, 84 (9.4%) on disease understanding, 218 (24.3%) on digital literacy, 63 (7.0%) on employment status, 104 (11.6%) on financial security, 89 (9.9%) on food security, 348 (38.8%) on caregiver support and 56 (6.3%) on access to care. Lower RPM engagement was associated with unfavorable digital literacy (β -0.05, p<0.001) and treatment understanding (β -0.1, p=0.004). Higher symptom burden was associated with unfavorable financial security (β 0.066, p=0.020) and disease understanding (β -0.1077, p=0.001), but favorable employment status (β 0.0497, p=0.025). Conclusions: RPM with ePROs offers an opportunity to screen for SDOH in routine care. The vast majority of pts enrolled had at least 1 unfavorable SDOH. Specific actionable unfavorable SDOH were associated with lower engagement and higher symptom burden. Personalizing RPM pathways according to SDOH may foster equitable care.

Clinicopathologic and genomic characteristics of patients with advanced ovarian, breast, and prostate cancer treated with poly (ADP-ribose) polymerase inhibitors (PARPi) in a real-world setting.

3159 Background: PARPis induce synthetic lethality in tumors that have homologous repair deficiencies (HRD). Due to relative rarity of HRD-related genomic and germline alterations across solid malignancies, it remains unclear which patients (pts) may derive most benefit from PARPis across different tumor types. Methods: We analyzed clinicopathologic and genomic characteristics of pts with advanced ovarian (OC, n=33), prostate (PC, n=28) and breast cancer (BC, n=13) treated with PARPi monotherapy at our institution. Only pts with HRD-related pathogenic alterations detected via next-generation sequencing of tumor tissue, with or without genetic susceptibility testing, were included. Results: Forty-one (55%) pts had a confirmed germline HRD-related gene alteration, of which 33 had BRCA1/2 and 8 had non-BRCA1/2 gene alterations. Average age of pts with BC was 54 years, OC 62 years, and PC 68 years. Median number of prior lines of therapy in the advanced setting was 1 (1-4) for OC and BC (0-7) and 3 (1-6) for PC. Median time to progression (TTP) in pts with OC was 8.3 months, BC 4.9 months and PC 3.6 months, likely due to i) majority of pts with OC received maintenance PARPi following favorable response to first-line chemotherapy, ii) pts with PC were older, and iii) more pts with PC had somatic rather than germline HRD-related mutations. Pts with germline vs somatic HRD mutation had longer median TTP in PC (5.0 vs 3.3 months) and BC (6.1 vs 4.0 months), but the opposite was true for OC (7.9 vs 10.8 months). Pathogenic TP53 mutations were identified in all but one pt with OC (32/33), 10/13 pts with BC, and 6/28 PCs. [table] Average TP53gene variant allele fraction (VAF) was similar in OC and BC (49.8% and 51.1%, respectively) but significantly lower in PC (26.4%), suggesting that TP53 mutations in PC were subclonal. No specific TP53 VAF or HRD-to- TP53 VAF ratio cut-off was associated with TTP or overall survival in any of the 3 cancer types. In addition, 7/28 (25%) of pts with PC had PTEN loss associated with modified response to PARPis, whereas none of the pts with BC had PTEN loss and only 3/13 had alterations of the PTEN/PI3K/AKTpathway. Conclusions: Double-strand DNA breaks caused by synergistic effects of aberrant TP53 and HRD-related genes can possibly explain the more favorable response of pts with OC and BC to PARPi, compared to those with PC. Co-alterations in other signaling pathways, epigenetic factors and/or tumor microenvironment likely play a role in the degree of response to PARPis, rather than TP53 clonality alone. In the era of expansion of genomic testing and new indications for PARPi larger genomic studies are needed to identify biomarkers of response to PARPi beyond HRD. [Table: see text]

Real-world treatment patterns and outcomes in US patients (pts) with advanced non-small cell lung cancer (NSCLC) after platinum-based chemotherapy (PBC) and anti–PD-(L)1 treatment.

8627 Background: Effective treatment options for advanced or metastatic NSCLC are limited, especially for pts who progress after treatment with PBC and an anti–programmed cell death 1 protein (PD-1) or ligand 1 (PD-L1) regimen. Examining real-world treatment patterns and long-term outcomes, we report on progression-free survival (PFS) and overall survival (OS) in pts with NSCLC who previously received PBC and anti–PD-(L)1 regimens. Methods: This study used the nationwide Flatiron Health electronic health record–derived deidentified database. Pts included in the analysis were ≥18 years old with an initial diagnosis of advanced or metastatic NSCLC and an ECOG PS of 0 or 1 who had received prior PBC and anti–PD-(L)1 therapy in 1 (in combination) or 2 (in sequence) lines and had initiated ≥1 subsequent line of treatment between 2018 and 2023; the start date of subsequent treatment (defined as the index regimen) was the index date. Pts were followed up until death or last available data through Mar 31, 2023. Pt characteristics, treatment patterns, and outcomes were analyzed for the overall pt group and according to initial treatment cohort (cohort 1: first-line [1L] PBC plus anti–PD-(L)1; cohort 2a: 1L PBC and second-line [2L] anti–PD-(L)1; or cohort 2b: 1L anti-PD-(L)1 and 2L PBC). PFS and OS were estimated using Kaplan-Meier methods. Results: Of 1793 pts, most were in cohort 1 (73.5%), with fewer pts in cohorts 2a (22.5%) and 2b (4.1%). The majority of pts in cohort 2b had PD-L1 ≥50% (n = 57, 78.1%), while the percentage was lower in cohorts 1 (n = 262, 19.9%) and 2a (n = 72, 17.9%). Most pts (n = 1626, 90.7%) had stage IV disease. Median time from advanced diagnosis to index date was 10.5 months (range, 1.1-103.8); median follow-up from index date was 7.8 months (range, 0.0-65.0). A broad range of treatments were used after PBC and anti–PD-(L)1 regimens; among all pts, the most common were docetaxel + ramucirumab and docetaxel monotherapy. Among all pts, median PFS and OS from the time of starting these index regimens were 5.29 and 11.20 months, respectively; PFS and OS were similar across cohorts. Conclusions: A broad range of subsequent treatments were used following PBC and anti–PD-(L)1 regimens, most commonly docetaxel with or without ramucirumab. Short median PFS and OS underscore a significant unmet need among pts previously treated with PBC and anti–PD-(L)1. [Table: see text]

A single center retrospective cohort study of patients with metastatic breast cancer and leptomeningeal disease: Updated survival data and subgroup analyses by breast cancer subtype.

1108 Background: Patients (pts) with metastatic breast cancer (MBC) and leptomeningeal disease (LMD) have a poor prognosis with limited therapies. We previously reported data from our retrospective LMD registry; here we provide an update with additional pts and subgroup analyses highlighting differences in treatment and survival by breast cancer subtype. Methods: In this single center retrospective cohort study, we identified pts with MBC and LMD who received care from 2000-2024 and abstracted key clinical, treatment, and overall survival (OS) data. Results: We identified 111 pts with MBC and LMD, including pts with the following subtypes: HR+/HER2- (n=53, 47.7%), HER2+ (n=30, 27.0%), and triple negative breast cancer (TNBC; n=28, 25.2%). The majority of pts had concurrent brain metastasis (n=82, 73.9%). Median time from diagnosis of MBC to LMD was 16.4 months (mo) (range 0-101.3 mo). Pts received a median of 3 lines of therapy prior to the diagnosis of LMD (range 0-10) and 1 line after the diagnosis of LMD (range 0-4). Most pts received central nervous system-directed (CNS)-directed therapy (n=94, 84.7%), including intrathecal (IT) therapy (n=42, 37.8%) and/or CNS radiation (n=70, 63.1%). Median OS from the diagnosis of LMD to death was 4.1 mo (range 0.1-78.1 mo) and varied by subtype, with pts with HR+/HER2- or HER2+ MBC and LMD living longer than those with TNBC and LMD (4.2 and 6.8 mo respectively vs. 2.0 mo, p<0.01, HR 2.15, 95% CI 1.36-3.39). There was no difference in OS by histology ductal vs. lobular or by presence or absence of concurrent parenchymal brain metastases. Pts who received IT therapy survived longer than those who did not (7.1 vs. 2.7 mo, p=0.01, HR 0.60, 95% CI 0.40-0.90). There was difference in OS by receipt of CNS-directed radiation therapy. Pts diagnosed with LMD from 2015-2024 lived longer than those diagnosed from 2000-2014 (6.4 vs. 2.9 mo, p=0.04, HR 0.67, 95% CI 0.46-0.99). On multivariable analysis, having TNBC was associated with shorter OS from time of LMD to death (p=0.004, HR 2.03, 95% CI 1.25-3.30). Conclusions: This study represents one of the largest case series of pts with MBC and LMD, including the most pts diagnosed after 2015 to our knowledge. Pts with lobular histology, HER2+ BC, TNBC, and those with de novo MBC were over-represented compared to the general MBC population. Pts with HR+/HER2- or HER2+ disease, LMD diagnosed after 2015, and those who received IT therapy survived longer than their respective cohorts. Novel diagnostic and therapeutic strategies for pts with MBC and LMD remains an area of unmet clinical need.

A portrait of germline pathogenic variants from a large real-world cohort of Brazilian patients with breast cancer.

10593 Background: The estimated prevalence of germline pathogenic/likely pathogenic variants (P/LP) in high and moderate penetrance (HMP) genes is around 7-10% among women with breast cancer (BC). Up to 50% of all hereditary BC cases are due to germline variants in BRCA1/2, but other HMP genes are increasing in relevance. The prevalence and spectrum of BC P/LP variants are affected by age at diagnosis, race/ethnicity, geographical region, BC molecular subtype. Methods: Retrospective cohort study to evaluate the germline profile of P/LP variants in HMP genes ( BRCA1, BRCA2, PALB2, TP53, CDH1, NF1, PTEN, STK11, CHEK2, ATM, BARD1, RAD51C and RAD51D) in women diagnosed with BC in Brazil. All patients were tested in a single reference laboratory (Oncoclinicas [OC] Precision Medicine) using multi-gene NGS panels covering from 35 to 105 genes. Primary endpoint was the prevalence of P/LP variants and VUS in BRCA1/2as well as in other HMP BC genes, in overall population and according to age and BC subtype. Clinical and pathological data were retrieved from curated Real-World Database of OC Group and used as reference for demographics comparisons. Results: This cohort involved 2,207 women with BC from 2019 to 2023. The majority of pts (79.7%) were from Southeastern Brazil, followed by Midwestern (5.6%), Southern (5.0%) and Northeastern (4.8%) Brazil. The median age at genetic testing was 47 years and most patients (59.4%) were ≤ 50 years. As reference, median age is 57 years in the overall BC population treated at OC (> 20,000 during the study period). BC subtype was available in 641 cases, 264 pts (41.2%) were HR+/HER2-, 116 (18.1%) were HER2+ and 261 (40.7%) were triple negative (TNBC). In the OC Database, TNBC represents only 15% of all new BC cases. Overall, 217 (9.8%) had a P/LP in HMP genes, including 131 (5.9%) pts who had a BRCA1/2 P/LP variant and 86 (3.9%) who had a P/LP variant in other HMP BC genes. The most frequent LP/PV variants were found in BRCA2 (31%) / BRCA1 (29%) / TP53 (13%) / PALB2 (9%) / CHEK2 (9%). A TP53founder pathogenic variant (R337H) accounted for 75% of all TP53 LP/PV. The deleterious variants were more common in pts ≤50 years (12%) than in pts > 50 (7%) as well as in patients with TNBC (14%) followed by HER2+ (9%) and HR+/HER2- (7%). The BRCA1/2 P/LP variants were higher in TNBC pts (8%) than in HR+/HER2- (4%) and HER2+ (3%). The overall VUS rate in the HMP genes was 20%. The most frequent VUS were found in ATM, BRCA2, NF1 and CHEK2genes. Conclusions: Studies involving germline profile of P/LP variants in cancer genes have provided a broader understanding of BC risk and have opened doors to new therapeutic or surveillance strategies across all subtypes. In Brazil, the prevalence of deleterious variants in HMP is comparable to published US and EU cohorts. However, in the real-world community practice, testing is still limited to populations with higher baseline risk for hereditary BC, such as young patients with TNBC.

Understanding breast cancer (BC) from the patient (pt) perspective: A qualitative study of symptoms, impacts and health-related quality of life (HRQoL) in hormone receptor-positive, HER2-negative (HR+, HER2–) BC.

e23184 Background: HR+, HER2– is the predominant BC subtype. Treatment (tx) options across stages are broad; however, there are limited published qualitative data providing insights on pt disease and tx experiences to inform healthcare decision-making. This study aimed to identify the most important disease- and tx-related symptoms and impacts on HRQoL, including exploring how bothersome and worrisome symptoms were, and attribution to tx and disease, in HR+, HER2– early (e) and metastatic (m)BC. Methods: This was an international qualitative study with pt steering committee input. Individual pt concept elicitation interviews were conducted (until saturation). Interviews were audio-recorded, translated into English, transcribed, and anonymized. Transcripts were coded and analyzed thematically. Two pt-centered conceptual models were developed to summarize data for eBC and mBC. Results: Twenty-four female pts (12 eBC; 12 mBC), aged 33–70 yrs old, were interviewed; 17 were postmenopausal. The most common tx was hormone therapy (n = 10) in eBC and cyclin-dependent kinase 4/6 inhibitors (n = 7) in mBC. The most frequently reported symptoms were fatigue (eBC n = 11; mBC n = 10) and pain (eBC n = 9; mBC n = 11). In eBC, fatigue was ranked most bothersome (n = 3) and pain most worrisome (n = 3). In mBC, pain was ranked most bothersome and worrisome (n = 7). In eBC, sleep problems, hot flashes, and difficulty concentrating/brain fog were also frequently reported (≥50% of pts) and ranked most bothersome. In mBC, sleep problems and hot flashes were also frequently reported (≥50% of pts), with hot flashes ranked most bothersome; nausea was less frequently reported but ranked most bothersome by two pts. The majority of pts with eBC attributed their most frequently reported symptoms to tx, whereas pts with mBC attributed them to tx alone or tx and their disease. The most frequently reported impacts in eBC were limited exercise/strenuous activity (n = 10), and fatigue, difficulty concentrating, and anxiety (n = 9 each). The most frequently reported impacts in mBC were limited participation in social activities (n = 10), and difficulties with activities of daily living, trouble with mobility, anxiety, and frustration (n = 9 each). Conclusions: These qualitative data highlight similarities in pt symptoms across eBC and mBC (pain and fatigue), with differences in symptom attribution. Compared with eBC, pts with mBC had greater physical functioning impairment and may have experienced more disease-related symptoms. Overall, these data improve understanding of pts’ experience in HR+, HER2– BC, identify the distinct and clinically relevant concepts most important to them, and can help to optimize the selection and development of pt-reported outcomes in research and clinical practice to further inform treatment decision-making.

Age and other criteria influencing nontreatment of patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC): Results of a physician survey in five European countries (Eu5).

4570 Background: Real-world studies have shown that a majority of pts with la/mUC do not receive first-line (1L) systemic therapy (tx), despite guideline recommendations. This cross-sectional study assessed the criteria that Eu5 physicians consider when making decisions about 1L tx for pts with la/mUC. Methods: A quantitative online survey of Eu5 physicians was performed in Aug-Sep 2022. Respondents answered questions related to demographics, practice patterns, and criteria considered in 1L decision-making. Descriptive statistics were used to analyze demographics and responses. Logistic regression was used to analyze physician characteristics associated with reporting no age threshold vs any age threshold when defining platinum ineligibility. Results: 503 physicians (69% oncologists and 31% urologists) completed the quota-based survey. Most respondents had been in practice for >10 years (69%) and treated 5-19 pts with la/mUC per month (58%) in public teaching hospitals (40%), public nonteaching hospitals (24%), and private hospitals (20%). Physicians estimated that they do not prescribe 1L tx for ≈25% of their pts. The majority of physicians selected advanced age (62.0%) and poor performance status (PS; 54.7%) as their top reasons for not prescribing 1L tx, followed by pt refusal (45.9%) and poor renal function (43.1%). Most physicians (78.1%) reported having an age threshold above which they recommend against 1L systemic tx (mean, 74.7 years old [Table]). After adjusting for baseline characteristics, physicians were more likely to have an age threshold if they were from Italy vs Germany (odds ratio [OR] 0.22 [95% CI 0.06-0.73]), practiced in a public nonteaching hospital (OR 0.28 [95% CI 0.10-0.73]) or public/private office settings (OR 0.14 [95% CI 0.03-0.57]) vs private hospital, and if they treated <20 pts/month (2-10 pts: OR 0.36 [95% CI, 0.17-0.74]; 11-19 pts: OR 0.25 [95% CI 0.09-0.62]). Conclusions: 1L systemic tx rates self-reported by Eu5 physicians were higher than those previously published. Many physicians reported having an age threshold for not offering systemic tx, which was relatively low compared with the senior age profile of the la/mUC population. Physicians who reported an explicit age threshold may be inappropriately excluding pts from tx; this could be a driver for systemic tx underutilization in la/mUC. [Table: see text]

A prospective study to evaluate the prevelance of chemobrain (CB) in patients (pts) receiving adjuvant treatment.

e23174 Background: Although adjuvant chemotherapy (CT) significantly improves the clinical outcome of pts with early-stage (ES) cancer, it is also known to cause side-effects. CT-induced cognitive impairment or CB refers to a clinical condition characterized by lack of mental sharpness, memory and concentration impairment and difficulty in processing information and executing simple tasks. Prospective data regarding the emergence of CB are limited. We aimed to explore the prevalence and predictors for CB among pts receiving adjuvant CT and to evaluate its impact on their quality of life (QoL). Methods: This was a prospective cohort study conducted at the University Hospital of Larissa. Pts who were recently diagnosed with ES breast (BC) or colorectal (CRC) cancer and were about to receive adjuvant CT containing doxorubicin (D) or oxaliplatin (O), respectively, were eligible for this study (C1). The first control group (C2) consisted of ES cancer pts that were not eligible for adjuvant CT and the second group (C3) was recruited from a pool of healthy controls (HCs). All participants (pcs) met the following inclusion criteria: age > 50 years old, ability to speak and write in Greek. Pts with pre-existing dementia/anxiety disorder and severe anemia were excluded from the study. Pts in C1 were assessed before receiving CT and 3 months after CT initiation. All subjects in C2 and C3 were assessed in 3 months intervals as well. After completion of the informed consent process, all pts and age-matched noncancer controls completed the Greek Version of Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) to specifically assess CB. QoL was measured using the EORTC QLQ-C30. Results: Overall, 82 pts (53 with BC and 29 with CRC) were included in C1, 36 pts (24 with BC and 12 with CRC) in C2 and 15 pcs in C3. At baseline, pts in C1 and C2 had significantly lower FACT-Cog scores than healthy controls in C3 (p: 0.028 and p:0.038, respectively), indicating a higher prevalence of self-reported cognitive impairment among pts with cancer after a curative surgery compared to age-matched HCs. However, after 3 months of CT the majority of pts in C1 (59/82, 72%) demonstrated a decline in their cognitive performance (35/53, 66% in BC pts receiving D and 24/29, 82% in CRC pts receiving O). Pts with CRC receiving O experienced more severe cognitive deficits. On the contrary, 55% of the pts in C2 (20/36, 16 with BC and 4 with CRC) demonstrated an improvement. The presence of CB (decline in cognitive functioning in the absence of severe anemia) was associated with decreased QoL (p = 0.004). Pts were mostly frustrated by the difficulty in executing simple tasks. Conclusions: As demonstrated in one of the largest cohorts of pts with ES cancer, CB is a common problem among pts receiving adjuvant CT and is associated with detrimental impact on daily life. Creating awareness is crucial to offer cancer survivors the best care directed at improving QoL.

Correlation between metastatic site and immunotherapy efficacy in patients with advanced dMMR/MSI colorectal cancer: Real-World Italian multicentric retrospective study (Colon-MSI).

e15544 Background: Immune checkpoint inhibitors (ICIs) are the gold standard therapy in metastatic colorectal cancer (mCRC) patients (pts) with microsatellite instability (MSI). The Colon-MSI study aimed to describe a cohort of MSI mCRC pts treated with ICIs before Italian pembrolizumab approval and to evaluate the efficacy, safety, and possible predictive factors of response in a real-world setting. Methods: We retrospectively collected data of pts with MSI mCRC treated with ICIs before June 30, 2023, in 16 Italian Cancer Centers. The OS was calculated from the diagnosis of metastatic disease, and the PFS from the beginning of ICIs. We explored the correlation between clinicopathological factors, survival outcomes, and treatment response. Results: Between January 2021 and June 2023, we reported 83 consecutive pts with data available. Among all, the median age was 61 years (23-86), 42 (51%) were female, and 45 (54%) had a ECOG PS 0; 35 (42%) pts were at stage IV at diagnosis, and 61 (74%) had right colon tumor site. The most common metastatic sites were liver (35%), lymph nodes (43%), peritoneum (31%), and lung (15%); 48 (58%) pts had a single metastatic site. 33 (39%) pts had a mucinous adenocarcinoma, 32 (39%) BRAF mutated, 32 (39%) RAS mutated, and 26% presented a Lynch syndrome. The majority of pts (69%) were pre-treated, and 26 pts (31%) received ICIs in first line. Nivolumab alone or plus Ipilimumab, and Pembrolizumab, were administered in 23 (28%), 3 (4%), and 57 (68%) pts, respectively. The median follow-up was 23 (1-65) months (m) and the median duration of treatment was 23 m (0-65) with 27 pts still ongoing. Treatment-related severe toxicities (G3 or G4) were observed only in 5.6% of pts. The median OS and PFS were not reached; the mean OS was 45.6 m (IC 95% 39.6-51.6) and the mean PFS was 38.8 m (IC 95% 32.5-45.1). Complete response (CR) was observed in 20 pts (24%), partial response (PR) in 28 (34%), stable disease (SD) in 19 (23%) and progression disease (PD) in 16 (19%). Overall response (ORR) was observed in 48 pts (57.8%; 95 %IC 0.31- 0.53), and disease control rate in 67 pts (80.7%; 95% IC 0.11– 0.29). Lung metastatic site was associated with poorer outcome in terms of OS (p = 0.001, HR 3.88 IC 95% 1.7-8.9), PFS (p = 0.045 HR = 2.31 IC95% 1-5.2), and ORR (p = 0.015 OR = 6.19 IC95% 1.4-26.9). Significantly worse PFS was also observed in pts with liver metastasis (p = 0.009 HR = 2.5 IC 95% 1.3-4.9). Conclusions: Our data confirm that ICIs are effective and well-tolerated treatment in MSI mCRC pts, with long-term clinical outcomes reported. These results suggest an unfavorable correlation between lung and liver metastasis and the ICI response. Further biomolecular analysis will be provided in the future.

Amivantamab plus lazertinib in atypical EGFR-mutated advanced non-small cell lung cancer (NSCLC): Results from CHRYSALIS-2.

8516 Background: Afatinib is the only EGFR tyrosine kinase inhibitor (TKI) approved to treat patients (pts) with EGFR-mutated advanced NSCLC harboring atypical mutations (eg, S768I, L861Q, G719X), excluding exon 20 insertion mutations (Ex20ins). In a retrospective analysis of 38 TKI-naïve pts, 27 had a response to afatinib, with a median duration of response (mDoR) of 11.1 months (mo) and median progression-free survival (mPFS) of 10.7 mo (Yang Lancet Oncol 2015;16(7):830-8). Amivantamab (ami) is an EGFR- MET bispecific antibody with immune-cell directing activity. Lazertinib (laz) is a CNS-penetrant, 3rd-generation EGFR TKI. This combination was evaluated among pts with atypical EGFR-mutated advanced NSCLC. Methods: Cohort C of the CHRYSALIS-2 study (NCT04077463) enrolled pts with atypical EGFR mutations, excluding Ex20ins, who were treatment-naïve or had ≤2 prior lines, which may have included a 1st/2nd-generation EGFR TKI. Pts with Ex19del or L858R co-mutations were excluded. Ami was intravenously administered at 1050 mg (1400 mg, ≥80 kg) weekly for the first 4 weeks and then biweekly. Laz was given orally at 240 mg daily. Response was assessed by the investigator per RECIST v1.1. Results: As of 4 Dec 2023, 105 pts received ami+laz, with a median follow-up of 13.8 mo (range, 0.1–30.2). The median age was 64 years, 50% were female, 68% Asian, 30% White, and 35% had CNS lesions at baseline. The most common mutations were G719X (54%), L861Q (24%), and S768I (22%). The ORR was 51% (95% CI, 41–61). In the treatment-naïve subset (n = 49), ORR was 55% (95% CI, 40–69), with mDoR not estimable (NE; 95% CI, 9.9 mo–NE) and mPFS of 19.5 mo (95% CI, 11.0–NE). Among responders, 78% (21/27) had DoR ≥6 mo. The ORR for pts harboring solitary mutations at G719 (n = 13), L861 (n = 8), and S768 (n = 2) was 54%, 63%, and 100%, respectively. The ORR for pts with compound atypical mutations (n = 17) was 41%, with DoR ≥6 mo for all 7 responders. Among pts treated with prior afatinib (n = 40), ORR was 45% (95% CI, 29–62), with mDoR of 8.9 mo (95% CI, 2.8–NE) and mPFS of 5.7 mo (95% CI, 4.2–10.7). Among the 18 responders, 56% had DoR ≥6 mo. The most common AEs were primarily EGFR- and MET-related toxicities, primarily grade 1-2. Discontinuations of both ami and laz due to treatment-related AEs occurred in 9% of pts. The incidence of VTE was 30% (31/105), with the majority of events, 71% (22/31), occurring in the first 4 mo of treatment. The vast majority of pts, 97% (30/31), were not on anticoagulation at time of first VTE. The rate of pneumonitis/interstitial lung disease was 6%. Biomarker analyses are ongoing; updated results will be presented at time of meeting. Conclusions: In the largest, single-cohort, prospective study of atypical EGFR-mutated advanced NSCLC, ami+laz demonstrated clinically meaningful and durable antitumor activity in pts who were treatment-naïve or had disease progression on afatinib. Clinical trial information: NCT04077463 .

Sugemalimab in locally advanced and advanced Chinese NSCLC: A real-world retrospective study.

e20575 Background: Lung cancer is a major cause of cancer deaths in China. Immunotherapy has emerged as a promising treatment approach for advanced NSCLC without sensitive mutations. Sugemalimab, a fully human immunoglobulin G4 monoclonal antibody, retains its Fc function, inducing antibody-dependent cellular phagocytosis. This study aims to evaluate the real-world effectiveness and safety of Sugemalimab in various treatment patterns, particularly with radiotherapy, in Chinese NSCLC patients with locally advanced or metastatic disease. Methods: We retrospectively evaluated locally advanced (LA-) and metastatic (m-) NSCLC patients (pts) treated with Sugemalimab in Cancer Hospital, Chinese Academy of Medical Sciences from Feb. 2022 to Sep. 2023. Demographic characteristics, clinical features, genetic landscape and therapy patterns were collected. We employed descriptive statistics to determine the Objective Response Rate (ORR) and Disease Control Rate (DCR), and used the Kaplan-Meier method for estimating Progression-Free Survival (PFS) and Overall Survival (OS). Safety profiles, including adverse events and immune-related pneumonitis, were similarly analyzed. Results: 76 pts with LA-NSCLC and mNSCLC were enrolled. Majority were male (92.1%) and smokers (84.2%) and ECOG PS 0-1 (78.9%). Median age was 66. Squamous-cell carcinoma was found in 44 pts (57.9%). The main metastatic sites were bone, brain, liver, lung and lymph node for mNSCLC pts. Genetic profiling in 39 pts revealed TP53 mutations in 19 (48.7%) and KRAS mutations in 10 (25.6%). A total of 38 pts (51.3%) received 1L Sugemalimab therapy, while 21 pts (27.6%) receiving 2L. Main treatment pattern was Sugemalimab plus platinum-based chemo. Radiotherapy (RT) was main local therapy approach, concurrent with Sugemalimab in 18 pts. Majority of pts received either volumetric modulated arc therapy or intensity-modulated radiation therapy to thoracic lesions. Tomotherapy was administered to brain metastases in 2 pts. The median follow-up time was 9.18m at this cut-off date. 16 pts receiving Sugemalimab plus chemo achieved objective response (ORR 44.4%) and DCR was 91.5% in 1L therapy. Median PFS (mPFS) has not been reached. PFS rate at 6m, 12m was 75.6%, 62.1% respectively. 1L OS was immature. For pts receiving additional thoracic RT concurrent with 1L systematic therapy, mPFS was still not mature. PFS rate was 82.4% at 6m and 74.9% at 12 m. Common RT-related side effects were radiation pneumonitis, radiation esophagitis and skin injury. None immune-related pneumonitis was found in this population. Only one case of immune-related pneumonitis was observed in a pts without RT. Conclusions: Our study demonstrated Sugemalimab-based therapy provide clinical benefits to LA-NSCLC and mNSCLC with good safety in real-world setting. The combination treatment of Sugemalimab with radiotherapy illustrates low pulmonary toxicity and superior tolerability.

Mutation profiles and outcomes of patients with acute myeloid leukemia with autoimmune disease.

6536 Background: Therapy-related acute myeloid leukemia (t-AML) defines a group of patients who develop AML after being treated with chemotherapy or radiation therapy. Most of these patients have a history of malignancy, but some have exposure to cytotoxic therapy for non-cancerous conditions such as autoimmune diseases (AD). This study looked at the characteristics, genetics, and outcomes of patients with AD and AML. Methods: This study included patients diagnosed with AML from 1999 - 2019. AML was divided into 4 groups: de novo AML, AD- AML (AML after AD diagnosis), t-AML (excluding AD-AML), secondary AML (s-AML) (AML arising out of myelodysplastic syndrome or myeloproliferative neoplasm). All molecular data were obtained via next generation sequencing (NGS) of genes frequently observed to be mutated in AML and analyzed using Chi-square test. BUM method was used to control false-discovery rate (FDR) at 8%. Overall survival (OS) and progression free survival (PFS) were estimated by Kaplan-Meier method and compared using log rank test. Results: A total of 1587 pts were included: 10.1% (n=160) with AD-AML, 71.3% (n=1131) de novo AML, 13.1% sAML (n=208) and 5.6% t-AML (n=88). The median age at diagnosis was 54.5 years; 54% were male; 67.3% received intensive induction therapy (Intensive defined as a 7+3 regimen). Cytogenetic (CG) data were available for 97.3% pts. According to MRC 2010 classification, CG were favorable in 14%, intermediate in 57%, and poor in 28% of the pts. The most prevalent AD were Crohn's/ulcerative colitis (n=30, 17%) and rheumatoid arthritis (n=23, 13%); 10.6% of pts had 2 disorders. In AD-AML group, the median age at diagnosis of first AD was 53 years; the median interval from AD diagnosis to AML was 82.5 months (mo); the majority of pts (56.25%) did not receive treatment (not including steroids) for their AD; 23.8% of pts were treated with immunomodulating agents, 23.1% with cytotoxic agents and 15% with anti-inflammatory agents; 20.1% received ≥ 2 drug classes. Poor risk CG were more common in AD-AML than in de novo AML (30% vs. 12.2%, p<.0001). Mutations in NF1 were more common in AD-AML (9.7%) than in de novo (2.7%), sAML (1.0%), and t-AML (2.7%, p=0.024). FLT3 mutations were less common in AD-AML (9.5%) than in de novo (36.1%) and t-AML (33.3%, p=0.004). Mutations in SRSF2 were more common in AD-AML (20.3%) than in de novo (12.3%) and sAML (8.8%, p=0.119). Median PFS varied among de novo (8 mo), AD-AML (6 mo) and t-AML (5 mo) groups. For the AD-AML grp, the median OS was 9 months; less than the de novo AML (11 mo), and greater than t-AML (6 mo) and sAML (6 mo, p<0.0001). Conclusions: Patients with AML and a prior history of AD have CG profile and outcomes similar to those with t-AML but with distinct molecular features (i.e. NF1 and SRSF2). These findings need to be validated in large series; however, they suggest that the MAPK signaling pathway as well as spliceosome inhibitors might be a future focus of investigation in pts with AD-AML.