Prior Therapy Research Articles

Treatment-free remission after discontinuation of tyrosine kinase inhibitors in patients with chronic myeloid leukemia in the chronic phase: a systematic review and meta-analysis

BackgroundTreatment-free remission (TFR) is a new long-term goal for treating selected patients with chronic myeloid leukemia in the chronic phase (CML-CP). Still, the appropriate group in which TFR can be attempted and the factors influencing it have not yet been identified. This meta-analysis aimed to explore TFR in CML-CP patients who achieved a deep molecular response (DMR) before Tyrosine kinase inhibitors (TKIs) discontinuation and to explore possible factors influencing TFR and the safety of discontinuation.MethodsWe performed a systematic review and single-arm meta-analysis with a systematic search of published literature up to September 2023 in PubMed, Embase, Web of Science, Cochrane Library, and CNKI databases. The assessment was performed using the MINORS scale. Random-effects models were used to calculate outcome metrics, including overall mean TFR rates at 12 and 24 months and subgroup differences. Data synthesis and analysis were done by Stata17.0 software.ResultsA total of 19 single-arm trials involving 2336 patients were included in this meta-analysis, with an overall mean TFR rate of 59% [95CI:0.56–0.63] at 12 months and 55% [95CI:0.52–0.59] at 24 months, and no CML-related deteriorations or deaths reported during the TFR period. Our subgroup analysis showed that better TFR was associated with prior interferon therapy (P = 0.003), and molecular response depth MR5.0 (P = 0.020).ConclusionOur study demonstrated that prior interferon therapy and attainment of a molecular response depth of MR5.0 or greater were associated with higher TFR rates, with patients who attained MR5.0 or greater achieving a TFR rate of up to 62% in the second year after TKI discontinuation. Considering the high heterogeneity of the included trials, the above influences still require further validation and more detailed subgroup analysis in future discontinuation trials.Systematic review registration:https://www.crd.york.ac.uk/prospero/ (Registration No. CRD42023471334).

Trastuzumab Duocarmazine in Pretreated Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Breast Cancer: An Open-Label, Randomized, Phase III Trial (TULIP).

Human epidermal growth factor receptor 2 (HER2)-targeted therapy is standard of care for HER2-positive (HER2+) breast cancer, but most patients develop progressive disease with persistent HER2 expression. No definitive treatment guidance currently exists beyond second line. Trastuzumab duocarmazine (T-Duo) is a third-generation, HER2-targeted antibody-drug conjugate that demonstrated efficacy and acceptable safety in phase I studies of heavily pretreated patients with HER2+/HER2-low breast cancer. In this open-label, randomized, phase III trial, T-Duo was compared with physician's choice (PC) in patients with unresectable locally advanced/metastatic HER2+ breast cancer with progression during/after ≥2 HER2-targeted therapies or after trastuzumab emtansine (T-DM1). The primary endpoint was progression-free survival (PFS) by blinded independent central review. In total, 437 patients were randomly assigned 2:1 to T-Duo (n = 291) or PC (n = 146). The median age was 56.0 years (range, 24-86); most patients (93.6%) had metastatic disease. The median time from diagnosis of metastatic disease to trial entry was 3.5 years; the median number of prior HER2-targeted therapies in metastatic setting was three. The median PFS was 7.0 months (95% CI, 5.4 to 7.2) with T-Duo versus 4.9 months (95% CI, 4.0 to 5.5; hazard ratio [HR], 0.64 [95% CI, 0.49 to 0.84]; P = .002) with PC. PFS benefit was maintained across most predefined subgroups. The median overall survival (first analysis) was 20.4 (T-Duo) versus 16.3 months (PC; HR, 0.83 [95% CI, 0.62 to 1.09]; P = .153). Objective response rate was 27.8% (T-Duo) versus 29.5% (PC); other efficacy end points-clinical benefit rate, duration of response, and reduction in target lesion measurement-tended to favor T-Duo. Grade ≥3 treatment-emergent adverse events occurred in 52.8% (T-Duo) versus 48.2% (PC). Treatment with T-Duo was manageable, but tolerability was affected by prevalent ocular toxicity, leading to a higher discontinuation rate in the T-Duo arm. T-Duo significantly reduced the risk of progression in patients with advanced HER2+ breast cancer who have progressed during/after ≥2 HER2-targeted therapies or after T-DM1.

Combined PD-1 and CTLA-4 Blockade in an International Cohort of Patients with Acral Lentiginous Melanoma.

Combination immune checkpoint blockade targeting PD-1 and CTLA-4 leads to high response rates and improved survival in advanced cutaneous melanoma (CM). Less is known about the efficacy of this combination in acral lentiginous melanoma (ALM). To determine the efficacy of combination immune checkpoint blockade targeting PD-1 and CTLA-4 in a real-world, diverse population of ALM. This multi-institutional retrospective study analyzed patients with histologically confirmed ALM treated with the combination of PD-1 and CTLA-4 inhibitors between 2010-2022. The primary objective of the study was objective response rate (ORR) per RECIST criteria. The secondary objectives were progression-free survival (PFS) and overall survival (OS). In total, 109 patients with advanced ALM treated with combined PD-1 and CTLA-4 blockade in any line of treatment were included. The majority of patients had stage IV disease (n=81, 74.2%). The ORR for the entire cohort was 18.3% (95% CI 11.6-26.9%), with 9 (8.3%) complete responses (CR) and 11 (10.1%) partial responses (PR). An additional 22 patients (20.2%) had stable disease (SD), and the disease control rate (DCR) was 38.5%. The median PFS was 4.2 months [95% CI 3.25-5.62], while the median OS was 17 months [95% CI 12.4%-23.1%]. A total of 95 patients (87.2%) had a treatment-related adverse event, with 40.4% (n=44/109) experiencing at least one grade 3 or 4 toxicity. Elevated LDH (p=.04), 2+ lines of prior therapy (p=.03), and Asian race/ethnicity (p=.04) were associated with worse OS, while Hispanic/Latino race/ethnicity was associated with better OS (p=.02). Combination of PD-1 and CTLA-4 blockade is less effective for ALM, as compared to CM, despite similar toxicity. Asian patients, in particular, appear to derive lower benefit from this regimen. Novel treatment approaches are needed for this rare melanoma subtype.

Evaluating the Effectiveness of Nivolumab in Metastatic Lung Cancer Among Patients Aged 65 and Older.

Background: Lung cancer remains the leading cause of cancer-related mortality globally, predominantly affecting older individuals. Despite the increasing use of immune checkpoint inhibitors (ICIs) like nivolumab in non-small cell lung cancer (NSCLC), the efficacy and safety in elderly patients, particularly those aged 65 and above, remain underexplored due to their underrepresentation in clinical trials. Methods: This retrospective study analyzed data from 60 elderly patients (≥65 years) with metastatic NSCLC who received nivolumab as second-line or later therapy between January 2020 and May 2023. Results: The median age was 67 years, with a predominance of males (78%). Nivolumab was administered for a median of 8 cycles, with 33.3% of patients receiving 15 or more cycles. The median OS was 23 months, and the 1-, 3-, and 5-year survival rates were 93.3, 54.1, and 18.6%, respectively. Multivariate analysis identified adenocarcinoma histology, fewer than 15 cycles of nivolumab, and non-response to prior therapies as independent predictors of poor OS. Nivolumab treatment was generally well-tolerated, with 45% of patients experiencing at least grade 1 toxicity. Conclusions: Nivolumab is effective and well-tolerated in elderly patients with metastatic NSCLC, providing survival benefits comparable to those observed in younger populations. The number of treatment cycles and initial response to therapy are key determinants of survival, underscoring the importance of continued treatment in this age group.

Strengths and Weaknesses of Different Therapeutic Strategies for the Treatment of Patients with Multiple Myeloma Who Progress After the Frontline Use of Lenalidomide: A Narrative Review

Background/Objectives: Patients with multiple myeloma (MM) who relapse after exposure to lenalidomide in the context of their first-line therapy are becoming a growing and clinically relevant population. We performed a systematic review of available clinical trials evaluating the efficacy and safety of different therapeutic strategies for the treatment of patients with MM at first relapse after the frontline use of lenalidomide. Methods: Publications of interest were searched on the PubMed database. The following search terms were employed: relapsed multiple myeloma, refractory multiple myeloma, first relapse, second-line therapy, lenalidomide-refractory (Len-R) and lenalidomide-exposed (Len-Exp). Results: Overall, triplet regimens that included anti-CD38 antibodies, carfilzomib and dexamethasone achieved a more favorable PFS regardless of the number of prior therapies. Other trials also demonstrated a non-negligible benefit with combinations containing pomalidomide, particularly in early lines of therapy. However, the variable number of patients with Len-Exp/Len-R disease enrolled in these studies and the limited number of those analyzed after progression following frontline lenalidomide make it difficult to select an “optimal” choice for the treatment of patients with MM at first relapse. Promising results have been more recently obtained by using combo therapies, including belantamab mafodotin and, above all, immunotherapies with CAR-T cells, and ongoing clinical trials are exploring the role of bispecific antibodies and CELMoDs in this population of patients. Conclusions: In the absence of clear-cut data regarding the specific effects of available regimens on patients with MM who are refractory or have relapsed after first-line therapies including lenalidomide, novel approaches based on different types of immune strategies are expected to further improve the clinical outcome of these patients.

Impact of Allogeneic Stem Cell Transplant on Safety and Outcomes of Chimeric Antigen Receptor T Cell (CAR-T) Therapy in Patients with Multiple Myeloma (MM).

Background: Allogeneic stem cell transplantation (allo-SCT) has seen limited use in treating multiple myeloma (MM), despite its potential to offer long-term survival or even cure through the graft-versus-myeloma effect. Its limited application is largely due to concerns over serious complications like infections and graft-versus-host disease (GVHD). The possibility of GVHD exacerbation when CAR-T cells are administered to patients previously treated with allo-SCT remains a topic of concern. Ciltacabtagene autoleucel (Cilta-cel) and idecabtagene vicleucel (Ide-cel) are CAR-T therapies that have been FDA-approved for relapsed/refractory (R/R) MM. A recent study using data from the CARTITUDE-1 trial has shown promising safety and efficacy of Cilta-Cel in patients with a prior history of allo-SCT. This report outlines our real-world experience with CAR-T treatment in such patients. The objective of this study is to assess the safety and effectiveness of CAR-T therapy in R/R MM patients who have previously undergone allo-SCT. Methods: We conducted a retrospective analysis of adult patients (18-70 years old) with R/R MM treated with CAR-T therapy as part of an institutional IRB-approved protocol. Data were collected on safety and efficacy outcomes from the institution's records. Adverse events (AEs) were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Efficacy metrics included overall response rate (ORR) and progression-free survival (PFS), analyzed through the Kaplan-Meier method, with PFS defined as the time from CAR-T initiation to disease progression or death. Results: Of the 56 patients treated with CAR-T therapy, 8 (14.3%) had previously undergone allo-SCT. These patients had a median of seven prior therapy lines (LOTs), compared to five LOTs in the non-allo-SCT group (p = 0.04). CAR-T infusion occurred a median of 98.8 months after allo-SCT, with a range from 57.9 months to 178.5 months. CRS occurred in 87.5% of the allo-SCT group versus 77.1% in the non-allo-SCT group (p = 0.48). One patient in the allo-SCT group developed hemophagocytic lymphohistiocytosis (HLH), requiring anakinra. At a median follow-up of 4.8 months, the ORR was 87.5% in the allo-SCT group versus 75% in the non-allo-SCT group (p = 0.4). Median PFS had not been reached for the allo-SCT group at the time of analysis compared to 11.9 months in the non-allo-SCT group (p = 0.5). No treatment-related mortality or acute GVHD was noted in the allo-SCT cohort. Conclusions: The study suggests that prior allo-SCT does not adversely affect the safety or efficacy of CAR-T therapy in patients with R/R MM. These findings highlight the need for further investigations with larger patient samples and longer follow-up to better understand the interaction between allo-SCT and CAR-T therapy.

SWOG/NCI Phase II Dual Anti-CTLA-4/PD-1 Blockade in Rare Tumors (DART): Non-Epithelial Ovarian Cancer.

The role of dual checkpoint inhibition in advanced rare/ultra-rare non-epithelial ovarian cancers (NEOCs) is yet to be explored. DART is a prospective, multicenter (1,016 US sites), multi-cohort, single-arm phase II trial conducted through the Early Therapeutics and Rare Cancer SWOG/NCI Committee, assessing ipilimumab (anti-CTLA-4) (1mg/kg every 6 weeks) and nivolumab (anti-PD-1) (240mg every 2 weeks) in adults with advanced NEOCs who lack beneficial standard therapy. Primary outcome was overall response rate [ORR; complete response (CR)/partial response (PR)]; secondary outcomes were progression-free survival (PFS), overall survival (OS), clinical benefit rate [CBR; stable disease (SD) ≥6 months plus ORR], and toxicity. Seventeen patients (median age: 64; number of prior therapies ranged from 0-8 with no immunotherapy exposure; 8 granulosa, 6 carcinosarcomas, 1 Sertoli-Leydig, 1 yolk sac, 1 Wolffian) were evaluated. In granulosa cell tumors, ORR was 25% (n=2/8; 1 CR, 1 PR) and CBR, 50% (n=4/8); PFS of 58.3 (CR), 50.7+ (PR), 30.4 (SD), and 8.7 (SD) months. Median PFS was 3.5 months (95% confidence intervals (CI) 1.7-11.2 months); median OS, 42.5 months (95% CI 10.1 months-not reached). One Sertoli-Leydig cell tumor showed a 22% regression (PFS 11.2 months). Carcinosarcomas had no response. Three participants (18%) discontinued treatment due to grade 3-4 adverse events. Ipilimumab-nivolumab shows activity in treatment-refractory granulosa cell tumors, with 25% (n=2/8) of patients experiencing either CR or PR lasting over 4 years.​.

P27.24.A SYSTEMIC AND LOCAL THERAPIES BEFORE AND AFTER DIAGNOSIS OF LEPTOMENINGEAL DISEASE IN PATIENTS WITH BRAIN METASTASES: AN EXPLORATIVE, SINGLE-CENTER RETROSPECTIVE COHORT STUDY

Abstract BACKGROUND Leptomeningeal metastasis (LMD), the dissemination of cancer cells into leptomeninges and/or cerebrospinal fluid, is believed to increase in incidence due to improved survival of oncological patients. Real-world data on therapies before and after diagnosis of LMD in brain metastasis patients are still limited. We aimed to characterize local and systemic therapies before and after diagnosis of LMD in these patients. MATERIAL AND METHODS We included 120 patients (treated from 2012 to 2023) with underlying solid malignancy, presence of brain metastasis together with leptomeningeal spread, either confirmed by MRI, cerebrospinal fluid sampling, or both modalities. Data on demographics, radiological, and therapy-related characteristics were collected. Kaplan-Meier estimates and Cox model regression analysis were performed to identify factors associated with survival. RESULTS Breast cancer (35.8%), NSCLC (20.8%), melanomas (16.7%), and gastric cancer (5.7%) were among the most common entities. In 56% of cases, the diagnosis was made by MRI, in 5% by cerebrospinal fluid puncture (LP) alone, and in 39% by both MRI and LP. The median overall survival (OS) of the cohort was 2.77 months [95% CI: 2.27 - 4.20]. Patients who received systemic after diagnosis of LMD, either chemotherapy (n=26), targeted therapies (n=21) or checkpoint inhibitors (n=9) showed increase survival as compared to respective control patients. The only independent prognostic factors at diagnosis of LMD were presence of lung cancer (HR: 2.36 [95% CI: 1.28 - 4.4], p=0.006) and melanoma (HR: 2.30 [95% CI: 1.27 - 4.2], p=0.006). Local or systemic treatment modalities before LMD diagnosis were not associated with survival. CONCLUSION This study provides insights into the complex treatment modalities for LMD patients, both in terms of prior therapies and therapies after diagnosis of LMD. These results underscore the need for large prospective multi-center registries and interventional studies to further improve interdisciplinary and personalized therapy for these patients.

Alopecia Areata Treatment Patterns and Satisfaction: Results of a Real-World Cross-Sectional Survey in Europe.

Alopecia areata (AA) is an autoimmune disease that causes scalp, face, and/or body hair loss. Recently, oral treatments with kinases inhibition became the first approved therapies for severe AA. An understanding of the use and effectiveness of traditional therapies in real-world treatment settings is needed to guide integration of novel therapies into the treatment paradigm. This study aimed to describe traditional treatment patterns, dermatologists' reasons for therapy choice, and dermatologists' satisfaction with disease control among patients with AA. Data were drawn from the 2021-2022 Adelphi Real World AA Disease Specific Programme™, a cross-sectional survey of dermatologists and adult patients with AA, conducted in France, Germany, Italy, Spain, and the UK. For each patient, using data from patient consultation and medical records, dermatologists reported % scalp hair loss (SHL), characteristics of current and prior AA therapies, and satisfaction with disease control. Overall, 239 dermatologists provided data for 1720 patients with AA. Mean (SD) patient age was 35.8 (11.6) years, and 51% were male. Based on dermatologist perception, among patients with ≤ 10% SHL, 74% were experiencing mild AA, while ≥ 95% of patients with ≥ 50% SHL were experiencing severe/very severe AA. In patients with ≥ 50% SHL, the most common therapies received included systemic immunosuppressants (31%), topical corticosteroids (24%), and oral corticosteroids (24%). Among all patients who had switched therapies, 49%, 26%, and 24% switched because of worsening AA, lack of initial efficacy with prior treatment, and loss of response over time, respectively. Among those with SHL ≥ 50%, dermatologists reported satisfaction with current therapy in < 30% of patients. Dermatologists reported low satisfaction with traditional AA therapies used in patients with extensive SHL, with some patients discontinuing treatment because of worsening disease. This suggests more effective treatments are needed for patients with severe AA.

Racial Disparities in Liver Transplant for Hepatitis C-Associated Hepatocellular Carcinoma.

In the United States, hepatitis C virus-associated hepatocellular carcinoma incidence and mortality are highest among minorities. Socioeconomic constraints play a major role in inequitable treatment. We evaluated the association between race/ethnicity and outcomes in a population that overcame treatment barriers. We report a retrospective cohort study of 666 patients across 20 institutions in the United States Hepatocellular Carcinoma Liver Transplantation Consortium from 2015 to 2019 with hepatitis C virus-associated hepatocellular carcinoma who completed direct-acting antiviral therapy and underwent liver transplantation. Patients were excluded if they had a prior liver transplantation, hepatocellular carcinoma recurrence, no prior liver-directed therapy, or if race/ethnicity data were unavailable. Patients were stratified by race/ethnicity. Primary outcomes were recurrence-free survival and overall survival, and secondary outcome was major postoperative complication. Race/ethnicity was not associated with differences in 5-year recurrence-free survival (White 90%, Black 88%, Hispanic 92%, Other 87%; p = 0.85), overall survival (White 85%, Black 84%, Hispanic 84%, Other 93%; p = 0.70), or major postoperative complication. Race/ethnicity was not associated with worse oncologic or postoperative outcomes among those who completed direct-acting antiviral therapy and underwent liver transplantation, suggesting that overcoming socioeconomic constraints equalizes outcomes across racial/ethnic groups. Eliminating barriers that prohibit care access among minorities must be a priority.

Therapeutic burden in hidradenitis suppurativa: a cross-sectional study of 557 patients.

Therapeutic burden (TB) has been identified as a potential predictor of response to biologic therapy in hidradenitis suppurativa (HS). We aim to analyze the determinants of TB in real-world clinical settings among HS patients to explain this concept and its utility as an additional tool for guiding therapeutic decision-making. We conducted a cross-sectional study including all consecutive HS patients attending a specialized HS clinic between 2017 and 2024. The primary variable was TB, defined as the cumulative sum of prior systemic treatment cycles and surgical interventions for HS. We analyzed whether sociodemographic or clinical factors were associated with a higher TB. We included 557 HS patients. Of these, 50.81% were women, and the mean age was 41.87 (14.19) years. Most patients (62.30%) were referred from general dermatology consultations. The mean disease duration was 17.52 (11.51) years. Regarding disease severity, 46.50% presented with Hurley II, and 42.19% had an IHS-4 score between 4 and 10. Before their baseline visit, 9.70% of patients had received biological therapy, mostly adalimumab (88.89%). The mean TB was 2.42 (2.25) systemic medical and/or surgical interventions. Referral from general dermatology or other hospital departments, older age, longer disease duration, greater HS severity, presence of pilonidal sinus, and prior biological therapy were significantly associated with higher TB. Our findings suggest that TB comprehensively captures HS severity and progression factors. This metric could prove valuable in aiding decision-making for HS patients by indicating when a change in therapy might be necessary.

WHOLE BRAIN RADIOTHERAPY FOR INTRACRANIAL METASTATIC DISEASE IN NON-SMALL CELL LUNG CANCER: THE WESSEX EXPERIENCE

Abstract AIMS The QUARTZ trial (2016) reported that corticosteroid therapy was non-inferior to whole brain radiotherapy(WBRT) for non-small cell lung cancer (NSCLC) with regards overall survival(OS). This is a single centre experience of WBRT for NSCLC in the post-QUARTZ era and in the context of the changes in clinical practice over the past 8 years. METHOD Single centre retrospective observational study. Patients included with NSCLC treated with WBRT for radiologically confirmed intracranial (IC) metastatic disease January 2018 to December 2022. OS, baseline tumour/patient characteristics and lines of treatment were recorded from medical records. Data compiled using Excel and statistical analysis using the R language for statistical programming. RESULTS 62 patients were included, median age 64 (37 -82). 29(46.8%) were Performance status 0-1. 50(80.6%) received 20Gy in 5 fractions, 12(19.4%) received 30Gy in 10 fractions. PDL1 &amp;gt;50% in 14(22.6%), EGFR mutation positive in 10(16.1%), 0(0%) ALK/ROS mutations. 9(14.5%) had received prior radiotherapy(RT) for IC disease (SRS:8, partial brain VMAT:1). 20(32.3%) had IC disease at presentation. Median OS 68 days (95%CI:58-111;range12-777) in keeping with QUARTZ results (median OS 65 days, 95%CI:50- 78). Univariate analyses demonstrated: subsequent systemic therapy (p=0.0022), receiving immunotherapy (p=0.002) and baseline performance status (p=0.0017) associated with improved OS. PDL1 &amp;gt;50%, EGFR mutation positive, RT dose, prior systemic therapy, histological subtype, presence of a targetable mutation, first or subsequent IC treatment did not predict survival. The chi-squared test was used to compare differences in the groups with OS&amp;gt;100days(n=22) and OS&amp;lt;100days(n=40). Systemic therapy after WBRT(p=0.0011) and immunotherapy treatment(p=0.0092) were significant differences between the cohorts and associated with improved survival. CONCLUSION This data supports conclusions of QUARTZ study and it remains difficult to define a role for WBRT in the management of IC disease in NSCLC. There is a cohort who have better OS, though we believe this may be related to systemic therapy (particularly immunotherapy) exposure.

Abemaciclib plus non-steroidal aromatase inhibitor or fulvestrant in women with HR+/HER2- advanced breast cancer: Final results of the randomized phase III MONARCH plus trial.

In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150mg twice daily [BID]) or placebo plus: anastrozole (1.0mg/day) or letrozole (2.5mg/day) (cohort A) or fulvestrant (500mg) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). In cohort A (abemaciclib: n =207; placebo: n =99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27months vs . 14.73months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n =104; placebo: n =53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41months vs . 5.59months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. ClinicalTrials.gov (NCT02763566).

Cross-Sectional Analysis of Patients Referred to a Tertiary Lymphatic Surgery Center.

Secondary lymphedema has become an increasingly common reason for referral to plastic surgery. Understanding referral patterns for lymphedema patients is crucial to optimizing care. Patients referred to plastic surgery for lymphedema at a lymphatic surgery center between January 2016 and 2023 were identified. Primary outcomes of interest included clinical lymphedema staging and characteristics, patient demographics, and referral sources. Secondary outcomes were prior lymphedema treatment, agreement between referring provider and plastic surgeon's diagnosis, and patient disposition after surgical evaluation. Descriptive statistics and multivariate logistic regression analysis were performed. A total of 285 patients with extremity edema were referred to plastic surgery; 60.0% of patients had prior malignancy, 45.6% of patients had undergone a prior lymph node procedure, and 40% had received radiation, while 56.8% of patients had previously seen occupational therapy. Body mass index (BMI, OR 1.09, p = 0.013), age (OR 1.25, p = 0.005), and prior physical oroccupational therapy (OR 1.23, p = 0.011) were associated with later stages of lymphedema upon presentation, while prior radiation (OR 0.79, p = 0.006) and malignancy (OR 0.85, p = 0.034) were associated with earlier stages of lymphedema. Self-referral (27.4%), primary care (17.9%), and medical oncology (14.7%) were the most common referral sources. Lymphedema was confirmed in 68.1% of referrals, and 28.5% of these patients proceeded to surgery. Patients were more likely to be operative candidates if referred by primary care (RR 2.1, p = 0.006) or occupational therapy (RR 4.6, p = 0.010). Referred patients ultimately undergo lymphedema surgery at relatively low rates, indicating that most referred patients are not ideal surgical candidates. Optimizing referral patterns through multidisciplinary education may enhance the referral process and improve access to lymphedema surgery.

Safety of Prior Propranolol Therapy for Infantile Hemangioma.

Propranolol has been the primary treatment for infantile hemangioma (IH) since 2008. Prior studies have investigated the effects in late childhood of propranolol therapy given in infancy for IH, including neurocognitive dysfunction, sleep disorders, and hypoglycemia. However, few studies have determined the risk of these adverse effects later in life. Using the TrinetX database, we studied the risk of growth impairment, sleep disorders, learning disabilities, and diabetes mellitus in children aged 10-17 years who had received propranolol for IH in infancy. The maximum age of 17 years was chosen for the study, as propranolol was established as a treatment for IH in 2008. The results showed no statistically significant risk of growth impairment, sleep disorders, learning disabilities, or diabetes mellitus in IH patients treated with propranolol. These findings support existing evidence that propranolol therapy given in infancy for IH is not associated with long-term adverse effects up to age 17 years in the studied patient population.

Updated overall survival and ctDNA analysis in patients with EGFR T790M-positive advanced non-small cell lung cancer treated with lazertinib in the phase 1/2 LASER201 study.

Lazertinib is a potent, irreversible, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with significant efficacy in patients with EGFR T790M-mutated non-small cell lung cancer (NSCLC). This is the final overall survival (OS) report from the phase 1/2 LASER201 study in patients with advanced NSCLC with disease progression on or after prior EGFR TKI therapy. Eligible patients were aged ≥ 20years, with advanced EGFR-mutated NSCLC and previous therapy with EGFR TKI. Patients in this integrated analysis received oral lazertinib 240mg/day. Endpoints included efficacy and safety; exploratory analyses included associations between circulating EGFR-mutant tumor DNA (ctDNA) and efficacy parameters. This integrated analysis included 78 patients in Korea who received second- or later-line lazertinib. The median OS was 38.9months; estimated survival rates at 12, 24, and 36months were 89.5%, 73.9%, and 52.8%, respectively. The cumulative 12-month incidence of central nervous system progression was 9.4%. EGFR-mutant ctDNA was detected in 46 patients (62.2%) at baseline. The presence of ctDNA at baseline significantly predicted progression-free survival (PFS), disease control rate (DCR), and OS. PFS, response rate, and DCR were significantly associated with EGFR-mutant ctDNA clearance at cycle 3; PFS and OS were significantly associated with ctDNA clearance at cycle 5. The safety profile of lazertinib 240mg/day was consistent with previous findings. Lazertinib is a promising treatment option for patients with EGFR T790M-positive NSCLC following disease progression on prior EGFR-directed TKIs. Patients in LASER201 experienced prolonged OS, regardless of their EGFR mutation, brain metastases, or prior brain radiation status. Clearance of plasma EGFR mutations after lazertinib was associated with patient outcomes. ClinicalTrials.gov identifier NCT03046992.

ChatGPT as a psychotherapist for anxiety disorders: An empirical study with anxiety patients.

Purpose: this study aims to investigate the role of ChatGPT as a psychotherapist for anxiety disorders, examining its effectiveness, acceptability, and potential benefits among individuals with anxiety disorders. Methods: a quasi-experimental design was adopted, involving a 4-week intervention where participants used ChatGPT as a therapeutic tool. The study included outpatients aged above 18 years from public hospitals in Saudi Arabia. A total of 399 participants completed a survey questionnaire that focused on their experiences with AI-based psychotherapy (six items), perceptions of ChatGPT (four items), and its role in different therapy modalities for anxiety management (seven items). Measures were taken to ensure the validity and reliability of responses by using Cronbach's alpha reliability testing (> 0.7), including the use of a translated and verified questionnaire. Results: majority received prior therapy (89.6%), reporting severe anxiety symptoms (36.1%). ChatGPT was widely used and perceived as accurate by 91.2% of users. Concerns included privacy (67.2%) and ethics (64.9%). Statistically significant differences (p < .05) in perceptions of ChatGPT for anxiety disorders were observed. While urban residents generally rated ChatGPT more positively, females consistently reported higher levels of trustworthiness, effectiveness, and coherence in guidance compared to males. Conclusion: ChatGPT has the potential to complement traditional psychotherapeutic approaches and enhance access to quality mental health care.

7959 Combination Therapy Of Multi-Targeted Tyrosine Kinase Inhibitors And Immune Checkpoint Inhibitors In Advanced Adrenocortical Carcinoma

Abstract Disclosure: F. Yaylaci Mert: None. V. Balderrama Brondani: None. L.P. Marcal: None. M. Campbell: None. C. Jimenez: None. J. Varghese: None. A. Shah: None. M.A. Habra: None. Background: Adrenocortical carcinoma (ACC) is a rare cancer with limited response to systemic chemotherapies. Monotherapy with multi-targeted tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) in ACC patients has limited efficacy. Combining TKIs with ICIs increased response rates in other malignancies but the efficacy of this approach in ACC is still unknown. This retrospective study aims to evaluate the efficacy and safety of the combined use of TKIs and ICIs in patients with advanced ACC. Methods: A single-center, retrospective cohort study in patients with advanced ACC treated with the combination of TKIs and ICIs. Response rates, progression-free survival (PFS), overall survival (OS) calculated from the time of combination, disease control rate (DCR), and safety profile were the main study objectives. Results: Seventeen patients were treated with combination therapy of TKI (lenvatinib or cabozantinib) and ICI (pembrolizumab) between January 2017 and December 2023. Eleven patients were women, the median age was 43.4 years (range 21.9-66.6), and 8 (47.1%) patients presented cortisol-producing tumors. All patients had prior systemic therapy, median of 3 (range 1-9) lines of therapy. The median duration of TKI+ICI therapy was 7.1 months (range 0.7-69.7). The treatment was discontinued in one patient due to a grade 3 adverse event (gastrointestinal fistula) after 1.6 months of treatment. Best overall responses were as follows: partial response 2 (13%), stable disease 8 (53%), and progressive disease 5 (34%). DCR was 58.8%. Median PFS was 7.1 months (range 0.7-66.4). One death occurred during the study due to disease progression. The median OS was 21.3 months (range 3.3-70.3). At the time of this report, 7 patients (41%) were still alive. Conclusion: The combined use of TKIs and ICIs in heavily treated ACC patients is associated with occasional durable responses and has a predictable and manageable side effect profile. This combination is worthy of a prospective clinical trial to validate the findings and establish new lines of therapy for this rare disease. Presentation: 6/2/2024

Proton beam therapy in a patient with secondary glioblastoma (32 years after postoperative irradiation of medulloblastoma): case report and literature review

ObjectiveThis report details the experience of a patient who developed a second primary glioblastoma (GB), offering insights into the treatment process and reviewing relevant literature.Case presentationA male patient, who was diagnosed with medulloblastoma at age 9, received treatment with cobalt-60 craniospinal irradiation (CSI) (36 Gy/20 fractions) and a tumor bed boost (total of 56 Gy). After 32 years, at age 41, an MRI revealed a space-occupying mass in the left cerebellar hemisphere. Surgical resection was performed, and postoperative pathology confirmed a diagnosis of radiation-induced glioblastoma (RIGB). Given the history of irradiation and the current tolerability of brainstem doses, proton beam therapy (PBT) combined with Temozolomide (75 mg/m2) was chosen. The treatment plan included 60 Gy on the gross tumor bed and 54 Gy on the clinical target volume, delivered in 30 fractions. The patient underwent regular follow-up and achieved a complete response.Clinical discussionFor childhood cancer survivors, the development of a second primary tumor significantly impacts prognosis. RIGB is a rare form of secondary tumor with distinct molecular characteristics compared to primary GB and recurrent secondary GB. Molecular markers such as IDH and MGMT status can help differentiate between primary GB, recurrent secondary GB, and radiation-induced secondary GB in patients with a history of prior radiation therapy. Surgical resection remains a primary treatment option, while PBT is preferred for postoperative treatment due to its superior protection of normal tissues and the ability to deliver high-dose irradiation.ConclusionRIGB is a rare second primary tumor that requires strategic molecular profiling and individualized management. Proton beam therapy provides effective high-dose irradiation in the postoperative phase and is the preferred treatment option for such cases.

7250 Effects of Romosozumab According To Prior Anti-Resorptive Treatments In Korean Postmenopausal Women From The Real-World Data: A Multi-Center Retrospective Study

Abstract Disclosure: Y. Kim: None. S. Ahn: None. S. Lee: None. S. Lee: None. H. Kim: None. S. Hong: None. Objectives: This study investigated the effects of romosozumab in Korean postmenopausal women based on their prior anti-resorptive treatments for osteoporosis from real-world data. Methods: A retrospective analysis of 145 postmenopausal women (66 drug-naïve [45.5%], 27 prior bisphosphonate [BP, 18.6%], 11 prior selective estrogen receptor modulator [SERM, 7.6%], and 41 prior denosumab [DMAB, 28.3%] groups) who received a 12-month romosozumab treatment between March 2020 and June 2023 at four hospitals in Korea was conducted. Changes in bone mineral densities (BMDs) at the lumbar spine (LS), total hip (TH), and femoral neck (FN), as well as bone turnover markers (C-telopeptide [CTX] and N-terminal type I procollagen propeptide [P1NP]), were evaluated. Results: Significant differences in BMD changes at all skeletal sites were observed between the groups (LS, TH, and FN: P&amp;lt;0.001, P&amp;lt;0.001, and P=0.018, respectively). Especially, the drug-naïve group showed a significantly greater increase in BMD change than the prior DMAB group at LS (17.5% vs. 6.5%, P&amp;lt;0.001), TH (4.8% vs. -0.2%, P&amp;lt;0.001), and FN (5.7% vs. 1.4%, P=0.015). The highest levels of P1NP were observed in the drug-naïve, prior BP, and prior SERM groups after one month of romosozumab treatment, while it was observed after six months in the prior DMAB group. Additionally, CTX levels decreased in the drug-naïve, prior BP, and prior SERM groups during romosozumab treatment, while an increase was observed in the prior DMAB group. Conclusion: The efficacy of romosozumab treatment is influenced by prior anti-resorptive therapies. Further investigation is necessary to develop personalized strategies for optimizing romosozumab's effectiveness based on prior osteoporosis medications, especially in prior DMAB group. Presentation: 6/3/2024