Subsequent Lines Of Treatment Research Articles

Telehealth-based, geriatric assessment-guided supportive care interventions (GAIN-S) for older adults with advanced cancer: A randomized clinical trial in Brazil.

215 Background: Older adults with cancer in developing countries often encounter obstacles in accessing specialized medical services. We conducted a randomized clinical trial to investigate the feasibility and preliminary efficacy of integrating telehealth-based multimodal geriatric assessment (GA)-guided supportive care interventions (GAIN) for older adults with advanced cancer in Brazil. Methods: Patients aged 65 and above with metastatic cancer receiving first- or subsequent-line treatment were recruited from Brazilian cancer practices and randomly assigned 1:1 to usual care or GAIN-S. Baseline assessments included telehealth-based measures of physical function (Instrumental Activities of Daily Living), depression symptoms (Geriatric Depression Scale), and quality of life (QOL, Functional Assessment of Cancer Therapy-General). The intervention group received multi-modal interventions entailed reviewing patients' needs based on baseline GA and providing remote consultation with supportive care services such as physical activity (supervised resistance, aerobic, and mobility exercises), nutrition, psychosocial support based on their needs. Usual care patients could be referred to the supportive care team upon request. Follow-up at 3 months included GA for both groups. Feasibility was defined as the proportion of patients who followed the intervention. T-tests were used to compare the means of two groups related to physical function, depression symptoms, and QOL. Results: Among 46 approached patients, 40 were included, with 20 allocated to each arm. Clinical characteristics were balanced between groups. Median age was 71 years (range: 65-88). Generally, patients were female (62%), married (57%), and had at least a college degree (52%). Breast (27%), gastrointestinal (22%), and genitourinary (15%) were the most common diagnoses. In the GAIN-S arm, 80% completed all aspects of the intervention, with few refusals (10%) and reports of worsened symptoms (5%). GAIN-S arm patients were most often referred for physical activity (85%), psychologists (55%), nutritionists (55%), and psychiatrists (20%). Notably, GAIN-S arm patients demonstrated significant improvements compared to control arm patients (Table). Conclusions: These findings highlight the feasibility and promising potential efficacy of integrating GAIN-S for older adults with advanced cancer. The significant improvements in physical function, depression symptoms, and QOL emphasize the importance of tailored supportive services and the potential of remote intervention in overcoming outcomes barriers and improving outcomes for older patients with cancer.[Table: see text]

Real-world treatment patterns and clinical outcomes post standard of care (SOC) among patients (pts) with metastatic non-small cell lung cancer (mNSCLC) with and without actionable genomic alterations (AGAs) in the United States (US).

534 Background: Initial treatment with immunotherapy (IO) and/or platinum-based chemotherapy (PBC) is SOC for patients (pts) with mNSCLC without AGAs (woAGA). SOC for pts with AGAs (wAGA) is targeted therapy, typically followed by PBC. There are limited treatment options and little real-world evidence on outcomes for pts who have experienced progression following SOC. This study characterized treatment patterns and clinical outcomes among pts with mNSCLC woAGA and wAGA after discontinuation of SOC therapies in the US. Methods: This retrospective observational study included pts with mNSCLC (≥18 years at diagnosis) from the ConcertAI Patient360 NSCLC EMR database (01/2015–09/2022). Pts were classified into 2 cohorts (wAGA and woAGA) based on positive or negative results from genetic testing for an AGA ( ALK, BRAF, EGFR, MET, NTRK, RET, KRAS, HER2 and/or ROS1). All pts were required to initiate a subsequent line of treatment (index LOT) after discontinuation of prior SOC therapies. Kaplan-Meier analysis was used to estimate median time to discontinuation (TTD), time to next treatment (TTNT), real-world progression free survival (PFS), and real-world overall survival (OS) for the index LOT. Results: The study included 1,386 pts woAGA and 349 pts wAGA. In the study cohort (woAGA vs wAGA), median age at index date was 67 vs 66 years, the median number of prior LOTs was 2 vs 3, 42.4% vs 63.6% were female, 74.5% vs 59.6% were treated in a community setting, 21.5% vs 34.2% had documentation of brain mets, and 92.3% vs 68% had ECOG ≤1. Among pts wAGA, 72% had an EGFR mutation. Median follow-up from index LOT initiation to end of study was 7 months for both groups. The most common index regimens among pts woAGA were non-PBC (44.8%), IO-based therapy (42.1%), and PBC (12%). Among pts wAGA, targeted therapies (35%), non-PBC (24.4%), and IO-based therapy (17.5%) were most often received in the index LOT. Docetaxel with or without ramucirumab was the most used index agent in both cohorts [pts woAGA (25.4%) and wAGA (10.6%)]. Median rwOS, rwPFS, TTD, and TTNT for index LOT are reported in Table 1. Conclusions: Following progression on SOC, pts with mNSCLC have limited treatment options and are predominantly treated with non-PBC (such as docetaxel ± ramucirumab) or rechallenged on previously used therapies. Observed treatment duration, PFS, and OS in this real-world setting were short and comparable to prior phase 3 trials, emphasizing the need for more effective treatment options among mNSCLC pts woAGA and wAGA post SOC therapies.[Table: see text]

Oligroprogression sous nivolumab du cancer bronchique non à petites cellules métastatiques traitées par radiothérapie

The prognosis of metastatic non-small cell lung cancer (NSCLC) has been improved by the use of immune checkpoint inhibitors (ICI). Unfortunately, in some cases, cancer cells will develop resistance mechanisms. In case of progression in a limited number of lesions (oligoprogression), focal treatment with radiotherapy is proposed while continuing the ICI therapy. A cohort of 37 patients with metastatic NSCLC treated with nivolumab (anti-PD-1) in second or subsequent line and who received focal radiotherapy for oligoprogression with continuation of nivolumab was compared with a control cohort of 87 patients no oligoprogressor treated par immunotherapy. After a median follow-up of 37months [18; 62], the median progression free survival (PFS) in the radiotherapy-treated cohort was 15.04 versus 5.04months in the control cohort, with a statistically significant difference (P=0.048). The median PFS following focal radiotherapy in the oligoprogressor group was 7.5months. In univariate analysis, the presence of lung metastasis was associated with increased PFS, in contrast to the presence of brain metastases, which were associated with decreased PFS in the radiotherapy group. The median overall survival was not reached in both groups, with no significant difference between the two cohorts. The combination of focal radiotherapy in case of oligoprogression and continued treatment with nivolumab in the treatment of metastatic NSCLC in the second or subsequent line of treatment seems to be with an increase in PFS.

Management and clinical outcomes of follicular lymphoma across continuous lines of treatments: a retrospective analysis in China

BackgroundFollicular lymphoma (FL) is characterized by an incurable course that frequently necessitates multiple lines of treatment. While a range of new approaches have broadened therapeutic options for patients in later lines, data regarding treatment patterns and outcomes of Chinese patients with relapsed/refractory(R/R) FL was scarcely reported.MethodsThis retrospective single-center study included patients diagnosed with FL grades 1–3a at our institution between January 2002 and December 2019. Endpoints of interest were analyzed according to lines and types of interventions. The endpoints mainly included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).ResultsThe study enrolled 566 biopsy-proven patients. Among them, 544 patients initiated the first line of treatment, followed by 240 initiating the second line, 146 initiating the third line, 88 initiating the fourth line, 47 initiating the fifth line, and 28 initiating the sixth line. In terms of treatment patterns, anti-CD20 chemotherapy was a major modality in the first and second lines. However, for patients in the third line and subsequent lines, treatment approaches were diverse, and participation in clinical trials for new medications was common, which correlated with a survival benefit. The study also revealed that clinical indicators (such as ORR, PFS, and OS) gradually decreased with each subsequent line of treatment. The ORR at the first line was 86.6%, but decreased to 48.6% at the third line and 40.4% at the sixth line, respectively. Similarly, median OS and PFS decreased to 88.8 and 7.1 months at the third line and further reduced to 21.7 and 2.8 months at the sixth line, respectively. A total of 133 patients developed progression within 24 months from the initiation of first line anti-CD20 chemotherapy (POD24), and these patients exhibited poorer response rates and outcomes in subsequent lines of therapycompared to the non-POD24 group.ConclusionThis study revealed the clinical routine practices and prognosis of R/R FL patients within the Chinese population. It underscored the unmet need for optimal strategies to improve survival and also served as a benchmark for future trials.

Outcomes for patients with EBV-positive PTLD post-allogeneic HCT after failure of rituximab-containing therapy

Epstein–Barr virus-positive (EBV+) post-transplant lymphoproliferative disease (PTLD) is an ultra-rare and aggressive condition that may occur following allogeneic hematopoietic cell transplant (HCT) due to immunosuppression. Approximately half of EBV+ PTLD cases are relapsed or refractory (R/R) to initial rituximab-containing therapy. There are limited treatment options and no standard of care for patients with R/R EBV+ PTLD, and little is known about their treatment history and outcomes. We performed a multinational, multicenter, retrospective chart review of patients with R/R EBV+ PTLD following HCT to describe patients’ demographic and disease characteristics, treatment history, and overall survival (OS) from rituximab failure. Among 81 patients who received initial treatment with rituximab as monotherapy (84.0%) or in combination with chemotherapy (16.0%), median time from HCT to PTLD diagnosis was 3.0 months and median OS was 0.7 months. Thirty-six patients received a subsequent line of treatment. The most frequent causes of death were PTLD (56.8%), graft-versus-host disease (13.5%) and treatment-related mortality (10.8%). In multivariate analysis, early PTLD onset and lack of response to initial treatment were associated with mortality. This real-world study demonstrates that the prognosis of patients with R/R EBV+ PTLD following HCT remains poor, highlighting the urgent unmet medical need in this population.

Longitudinal assessment of plasma androgen receptor copy number predicts overall survival in subsequent treatment lines in castration-resistant prostate cancer: analysis from a prospective trial

Baseline plasma androgen-receptor copy number (AR-CN) is a promising biomarker for metastatic castration-resistant prostate cancer (mCRPC) outcome and treatment response; however, the role of its longitudinal testing is unproven. We aimed to evaluate the prognostic role of AR-CN assessed before subsequent treatment lines in mCRPC patients. A subgroup analysis of a prospective multicenter biomarker trial (IRSTB030) was carried out. Plasma AR-CN status (classified as normal or gain, cut-off value= 2) was assessed with digital PCR before each treatment line. Forty mCRPC patients receiving sequentially docetaxel, cabazitaxel and an AR signaling inhibitor (abiraterone or enzalutamide) were analyzed. At multivariate analysis, at each assessment overall survival (OS) was independently correlated with AR-CN status [first line: hazard ratio (HR) 4.1 [95% confidence interval (CI) 1.6-10.5]; second line: HR 2.4 (95% CI 1.1-5.3); third line: HR 2.1 (95% CI 1.0-4.3)] and median prostate-specific antigen [first line: HR 4.4 (95% CI 1.8-10.9); second line: HR 3.4 (95% CI 1.6-7.2); third line: HR 2.5 (95% CI 1.2-5.6)]. In the three subsequent assessments, AR-CN status changed from normal to gain in 15 (38%) patients. These patients had longer OS (47 months) compared with patients presenting AR-CN gain from first assessment (36 months), but shorter than those maintaining normal AR-CN (69 months) (P= 0.003). Plasma AR-CN correlates with survival not only at baseline (before first treatment), but also in the assessments before the following lines. Interestingly, AR-CN status may change from normal to gain across subsequent treatments in a significant number of cases, identifying a group of patients with intermediate outcomes. Longitudinal assessment of AR-CN status could represent a promising method to capture mCRPC intrinsic heterogeneity and to improve clinical management.

Quad-class exposed/refractory myeloma is associated with short survival.

Very scarce data exist about outcomes of relapsed multiple myeloma patients who have failed proteasome inhibitor, immunomodulatory drug, anti-CD38 monoclonal antibody and therapies targeting B-cell maturation antigen (BCMA) (Quad-class exposed [QCE]). In this retrospective single-centre study, we determined progression-free survival (PFS) and overall survival (OS) from anti-BCMA failure in 45 QCE patients. Seven (16%) patients received antibody-drug conjugate, 20 (44%) bispecific antibodies and 18 (40%) CAR-T cell. Thirty patients (67%) received ≥1 subsequent line of treatment. PFS was 4.4 months (95% CI = 2.4-12.5) and OS 6.3 months (95% CI = 3.9-14.4). Having an adverse prognosis, QCE myeloma patients remain an unmet medical need.

Real-World Data on the Diagnosis, Treatment, and Management of Hepatocellular Carcinoma in the Asia-Pacific: The INSIGHT Study

Introduction: Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and the third leading cause of cancer death worldwide. While there has been rapid evolution in the treatment paradigm of HCC across the past decade, the extent to which these newly approved therapies are utilized in clinical practice in the real world is, however, unknown. The INSIGHT study was an investigator-initiated, multi-site longitudinal cohort study conducted to reflect real-world epidemiology and clinical practice in Asia-Pacific in the immediate 7-year period after the conclusion of the BRIDGE study. Methods: Data were collected both retrospectively (planned 30% of the total cohort size) and prospectively (planned 70%) from January 2013 to December 2019 from eligible patients newly diagnosed with HCC from 33 participating sites across 9 Asia-Pacific countries. Results: A total of 2,533 newly diagnosed HCC patients (1,052 in retrospective cohort and 1,481 in prospective cohort) were enrolled. The most common risk factor was hepatitis B in all countries except Japan, Australia, and New Zealand, where the prevalence of hepatitis C and diabetes were more common. The top three comorbidities reported in the INSIGHT study include cirrhosis, hypertension, and diabetes. We observe high heterogeneity in the first-line treatment recorded across countries and across disease stages, which significantly affects survival outcomes. Stratification by factors such as etiologies, tumor characteristics, the presence of extrahepatic metastases or macrovascular invasion, and the use of subsequent lines of treatment were performed. Conclusion: The INSIGHT study describes a wide spectrum of clinical management practices in HCC, where patient demographics, differential costs, and patient access to therapies may lead to wide geographical variations through the patient’s treatment cycle, from diagnosis to clinical outcome. The high heterogeneity in patient outcomes demonstrates the need for more robust and clinical management strategies to be designed and adopted to bring about better patient outcomes.

Metabolic Syndrome: The Constellation of Co-morbidities, a Global Threat.

Metabolic syndrome, also referred to as Syndrome X or obesity syndrome is a cluster of diseases prevalent worldwide in both developed and developing countries. According to WHO, it is referred to as a pathological condition wherein multiple disorders are manifested in the same individual. These include hypertension, hyperglycemia, dyslipidemia and abdominal obesity. Metabolic syndrome is one of the most serious non-communicable health hazards that have gained pivotal importance in the present scenario. The increasing prevalence affecting around 25 % of the world populace, mainly attributes to the acceptance of western culture, i.e. the intake of high-calorie food along with a substantial decrease in manual labor and adoption of sedentary lifestyles. Therefore, its timely prevention and management are the dire need in the present scenario. For successful accomplishment of the present review, an exhaustive analysis was performed utilizing a pool of previous related literature. The terms used during the search included 'metabolic syndrome, prevalence, etiology, current pharmacotherapy for metabolic syndrome, etc. PUBMED, Medline and SCOPUS were explored for the study of abstracts, research and review papers in the quest for related data. The articles were downloaded and utilized for a meta-analysis study approach. In this review, an attempt was made to apprehend and summarize the epidemiology and treatment strategies for metabolic syndrome with a better understanding of its pathogenesis. It was postulated that an early diagnostic approach and subsequent line of treatment is required to prevent the deterioration of an individual's health and life.

Selected-Lesion Stereotactic Radiosurgery in Treatment of Patients with Multiple Brain Metastases: A Single Institution Retrospective Study

Stereotactic Radiosurgery (SRS) has been increasingly used as first and subsequent-line treatments for brain metastases. While the appropriate cut-off number of lesions for SRS is still being debated nationally in patients with multiple brain metastases, some institutions use an alternate approach particularly for patients with >10-15 lesions. Selected-lesion SRS (SL-SRS) is where only a subset of lesions are chosen for initial SRS treatment leaving small and clinically inconsequential lesions for treatment using alternate or delayed treatments. This study aims to investigate the patient selection criteria, patient and tumor characteristics and analyze the outcomes in patients receiving SL-SRS for brain metastases at our institution. Clinical data from patients treated using the SL-SRS approach from 2012-2022 at our institution were retrospectively reviewed. Patients were divided into cohorts based on overall survival from time of SL-SRS treatment and indications for using SL-SRS. We compared the patient characteristics (age, histology, KPS, dsGPA), tumor characteristics (cumulative tumor volumes, tumor dose, number of brain metastases found, number of metastases treated), treatment characteristics (chemotherapy, immunotherapy, previous SRS/ radiation, previous WBRT) and the reason for decision to recommend SL-SRS across these cohort. A total of 102 patients were treated using the SL-SRS approach. Indications for using SL-SRS were immunotherapy trial (n = 40), CNS penetrating drug options available (n = 18), patient refusing WBRT (n = 6), palliative after prior WBRT/SRS (n = 28), WBRT planned to follow SRS (n = 9). 31 patients were alive at 12 months and 21 patients at 24 months. In patients surviving <12 months - the most common indications for SL-SRS were CNS palliation in the setting of progressive disease after prior WBRT or SRS. Patients in this group had median KPS< = 60 and had predominantly non-small cell carcinoma primary diagnosis. In those patients surviving >12 months - the most common indication for SL-SRS was participation in CNS-penetrant agent clinical trials without WBRT. Patients in this group were more likely to be female, had a median KPS of 90, had predominantly diagnoses of melanoma. Following the SL-SRS treatment, 14 patients required further SRS and 4 patients went on to WBRT in the >12-month survival group. No patients died of CNS progression alone. 10 patients survived 24 months without requiring further CNS radiation. In our institution, SL-SRS has predominantly been used either as palliative treatment at time of disease progression or to facilitate entry onto clinical trial with immunotherapy or potentially CNS-penetrant agents. The latter indication resulted in 47.6% patients surviving >24 month without the need for additional radiation to the CNS and therefore SL-SRS should be considered a feasible, safe and effective alternative to either WBRT or SRS treatment of all radiographically visible brain metastases.

Immune Checkpoint Inhibitors in Metastatic Bladder and Other Solid Malignancies: How Long is Enough?

The introduction of T-cell targeted immunomodulators blocking the PD-1 and PD-L1 axis is unquestionably one of the most notable advancements in the treatment of advanced or metastatic solid malignancies, including bladder cancer. Immune checkpoint antibodies are now widely utilized as monotherapies or in combination with other systemic therapies in the first or subsequent lines of treatment in approximately 50 cancer types. Deep and durable responses and long tails of survival curves are hallmarks of patients treated with immune checkpoint inhibitors. However, treatment can have negative impacts, including serious treatment-related side effects as well as a high financial burden to individual patients and the healthcare system. There is increasing data that the benefit of immune checkpoint treatment may persist after treatment is discontinued for reasons other than progressive disease, particularly in patients who have achieved a durable complete response. However, the optimal treatment duration and activity after treatment reinitiation remains undefined and will likely be influenced by disease biology (histology and genomics), treatment (monotherapy or combination therapy), and disease context (depth and duration of response). Well-designed prospective clinical trials and the development and validation of biomarkers that predict outcomes after treatment cessation are needed to move the field forward.

Clinical and economic implications of epilepsy management across treatment lines in Spain: a real-life database analysis

BackgroundEpilepsy is a chronic brain disease characterized by recurrent seizures. We investigated real-world management of epilepsy across treatment lines in Spain, including healthcare resource use (HRU) and associated costs.MethodsThis was a retrospective study of real-life data from epilepsy patients prescribed antiseizure medication (ASM) between January 2016 and December 2021. Patients were grouped according to their line of treatment (1st, 2nd, 3rd and 4th +) during the recruitment period. Demographic and clinical characteristics, comorbidities and concomitant medications were analyzed during the baseline period (6 months before starting treatment line); antiepileptic treatments, concomitant medications, HRU and associated costs were analyzed during follow-up.ResultsThe study included 5006 patients. Treatment duration decreased as treatment lines progressed (mean ± SD progression time: 523.2 ± 279.1 days from 1st to 2nd line, 351.6 ± 194.4 days from 2nd to 3rd line; 272.7 ± 139.3 days from 3rd to 4th + line). Significant HRU differences were found with subsequent treatment lines, including an increase in hospital admissions and patients on sick leave. Mean (95% CI) adjusted total costs per patient were €2974/year (2773–3175) in the 1st line and €5735/year (5043–6428) in the 4th + line. There was an increase in adjusted direct and total costs with subsequent treatment lines; the mean difference in total costs between cohorts was €2761 (p < 0.001). The highest direct costs were associated with epilepsy medication, days at the hospital and specialist visits.ConclusionOur data revealed a progressive increase in the use of resources and associated costs across subsequent epilepsy treatment lines.

Safety and toxicity of cabozantinib monotherapy in patients with advanced renal cell carcinoma: a Russian multicenter observational study

Aim. To assess the safety and to analyze an influence of cabozantinib monotherapy toxicity on treatment efficacy in unselected Russian patients with metastatic renal cell carcinoma (mRCC).&#x0D; Materials and methods. Medical data of 92 patients with verified mRCC were included in the study. The median age of the patients was 56 (1979) years, most of them - 60 (65.2%) were of male gender. Twenty five (27.2%) persons had Eastern Cooperative Oncology Group performance status (ECOG PS). At the time of cabozantinib monotherapy start 5 (5.4%) patients had favorable, 54 (58.7%) intermediate, and 33 (35.9%) unfavorable prognosis by International Metastatic Renal Cancer Database Consortium (IMDC) model. Eighty-three (90.2%) patients were pretreated, including 76 (82.6%) patients who previously received anti-angiogenic agents. All patients were administered with cabozantinib monotherapy (60 mg/day); dose adjustment was performed according to the instruction.&#x0D; Results. Adverse events (AEs) were reported in 81 (88.0%) of 92 patients; 30 (32.6%) AEs were grade 34. Toxicity-related dose reduction of cabozantinib was required in 28 (30.4%), treatment interruption in 15 (16.3%), and discontinuation in 2 (2.2%) patients. The most common AEs were hypertension (69 patients, 75.0%), asthenia (47 patients, 51.1%), diarrhea (43 patients, 46.7%), and palmar-plantar erythrodysesthesia (43 patients, 46.7%). The most common severe AEs were: arterial hypertension (17 patients, 18.5%), diarrhea (6 patients, 6.5%), and palmar-plantar erythrodysesthesia (2 patients, 2.2%). The most frequent laboratory abnormalities during therapy were elevated serum transaminases (33 patients, 35.9%), anemia (13 patients, 14.1%), and thrombocytopenia (10 patients, 10.9%). No previously unreported AEs or laboratory abnormalities were observed. There was a significant increase in progression-free survival (hazard ratio 2.5; 95% confidence interval 1.05.9; p=0.046) and overall survival (hazard ratio 3.0; 95% confidence interval 1.28.3; p0.025) in patients with treatment-related arterial hypertension.&#x0D; Conclusion. The observational study confirmed the acceptable safety profile of cabozantinib in the first and subsequent lines of treatment in mRCC patients. No new safety signals were identified. Treatment-related arterial hypertension may be a favorable predictor of survival.

Помалидомид в терапии рецидивирующей/рефрактерной множественной миеломы

Pomalidomide is a third-generation immunomodulatory drug (IMiD) that has taken an important place in the management of relapsed/refractory multiple myeloma (RRMM) including in patients with resistance to lenalidomide (R). Synergism of antitumor activity was obtained by combining pomalidomide with dexamethasone (Pd), proteasome inhibitors (PIs), and monoclonal antibodies directed against CD38 and SLAMF7 receptors. The dose-limiting toxicity of pomalidomide is neutropenia (4860% grade 3 for a dose of 4 mg/day). Overcoming resistance to lenalidomide is seen as a key benefit of pomalidomide in the development of triplets that can be used in 2nd and subsequent lines of RRMM treatment. In OPTIMISMM study (phase III), 70% of patients were lenalidomide resistant. Randomization was performed on VPd (bortezomib-Pd) and Vd (bortezomib, dexamethasone) therapy. Vd as control was implemented in two related phases III trials ENDEAVOR (carfilzomib, dexamethasone) and CASTOR (daratumumab-Vd). For patients with resistance to lenalidomide, the median progression-free survival (PFS) was 9.5 mon for VPd in OPTIMISMM; 9.3 mon in CASTOR (resistant to R 21%) for DVd, and 9.3 mon in ENDEAVOR (21%) for Kd - 8.6 mon. The ICARIA-MM study (phase 3; resistance to R 94%) demonstrated the benefit of incorporating isutaximab into the triplet (median PFS 11.1 and 5.9 mon for Isa-Pd and Pd respectively; p0.0001). Similar data were obtained in the ELOQUENT-3 study (phase II; resistance to R - 90%) for elotuzumab (10.3 and 4.7 mon for EPd and Pd respectively; p=0.008). In the APOLLO study (phase III; resistance - 80%), the efficacy of the triplet with daratumumab was confirmed (12.4 and 6.9 mon for DPd and Pd respectively; p = 0.0018). In the present review, the focus is on the consideration of treatment regimens that are of relevance to Russian clinical practice.

Cost-effectiveness analysis of trastuzumab deruxtecan in patients with HER2-low advanced breast cancer based on DESTINY-Breast04.

Breast cancer is a rapidly raising healthcare problem worldwide. DESTINY-Breast04 demonstrated that trastuzumab deruxtecan (T-Dxd) had a survival advantage comparing to the physician's choice of chemotherapy for patients with HER2-low metastatic breast cancer. But at the same time, this expensive novel treatment also brought an economic burden. This study assessed the cost-effectiveness of T-Dxd based on results of DESTINY-Breast04 from the perspective of Chinese healthcare system. A three-state partitioned-survival model [progression-free survival (PFS), progressive disease (PD) and death] based on data from DESTINY-Breast04 and Chinese healthcare system was used to estimate the incremental cost-effectiveness ratio (ICER) of T-Dxd vs. the physician's choice of chemotherapy for HER2-low metastatic breast cancer. Costs, quality-adjusted life-years (QALYs) and the ICER in terms of 2022 US$ per QALY gained were calculated for both hormone receptor-positive cohort and all patients. One-way and probabilistic sensitivity analyses were performed to assess the model robustness. Compared with the physician's choice of chemotherapy, T-Dxd increased costs by $104,168.30, while gaining 0.31 QALYs, resulting in an ICER of $336,026.77 per QALY in all patients. The costs of T-Dxd and the utility of PFS were the crucial factors in determining the ICER. In the hormone receptor-positive cohort, the ICER was lower than that in all patients, with the ICER of $274,905.72 per QALY. The ICER was much higher than the commonly accepted willingness-to-pay threshold ($357,96.83 per QALY). T-Dxd as second- or subsequent-line treatment is not a cost-effective treatment option for HER2-low metastatic breast cancer from the perspective of the Chinese healthcare system.

Panitumumab plus trifluridine/tipiracil as anti-EGFR rechallenge therapy in patients with refractory RAS wild-type metastatic colorectal cancer: Overall survival and subgroup analysis of the randomized phase II VELO trial.

The randomized phase II VELO trial showed that the addition of panitumumab to trifluridine/tipiracil significantly improves progression-free survival (PFS) as compared to trifluridine/tipiracil in third-line therapy in patients with refractory RAS wild-type (WT) metastatic colorectal cancer (mCRC). With longer follow-up, final overall survival results and posttreatment subgroup analysis are presented. Sixty-two patients with refractory RAS WT mCRC were randomly assigned to receive, as third-line therapy, trifluridine/tipiracil alone (arm A) or in combination with panitumumab (arm B). Primary endpoint was PFS; secondary endpoints included overall survival (OS) and overall response rate (ORR). Median OS was 13.1 months (95% CI 9.5-16.7) in arm A compared to 11.6 months (95% CI 6.3-17.0) in arm B (HR: 0.96, 95% CI 0.54-1.71, P = .9). To evaluate the impact of subsequent lines of treatment, subgroup analysis was performed for the 24/30 patients in arm A, that received fourth-line therapy after disease progression. Median PFS was 4.1 months (95% CI 1.44-6.83) for 17 patients treated with anti-EGFR rechallenge as compared to 3.0 months (95% CI 1.61-4.31) for seven patients that received other therapies (HR: 0.29, 95% CI 0.10-0.85, P = .024). Median OS from the start of fourth-line treatment was 13.6 months (95% CI 7.2-20), and 5.1 months (95% CI 1.8-8.3) for patients treated with anti-EGFR rechallenge vs other therapies, respectively (HR: 0.30, 95% CI 0.11-0.81, P = .019). Final results of the VELO trial support the role of anti-EGFR rechallenge in the continuum of care of patients with RAS/BRAF WT mCRC.

Real-world outcomes of long-term efficacy of T-DM1 after discontinuation due to limiting toxicity in patients with HER2-positive metastatic breast cancer.

e13034 Background: Antibody-drug conjugates (ADC) are widely used in the treatment of breast cancer (BC). In our service, we observed that a significant number of patients (pts) with HER2-positive metastatic breast cancer (MBC) treated with T-DM1 had long-lasting response and survival rates, even after discontinuing T-DM1 due to limiting toxicity. However, data are scarce regarding its long-term benefit. We performed a retrospective study to evaluate the long-term efficacy of T-DM1 in the treatment of HER2-positive MBC. Methods: Medical records of pts with HER2-positive MBC treated with T-DM1 between September 2013 and January 2023 were reviewed. We analyzed data in the overall population and in the subgroup of pts who discontinued T-DM1 due to only limiting toxicity and did not have disease progression or death for at least 12 months, without receiving other subsequent lines of treatment. The primary endpoints were progression-free survival (PFS) and overall survival (OS) from the start of the treatment with T-DM1 to disease progression or death for the overall population, and from the time of T-DM1 discontinuation to disease progression or death for the aforementioned subgroup. Secondary endpoints were objective response rate (ORR) and toxicity. Results: A total of 73 pts were included. In the overall population, ORR was 82.6%, median PFS was 12.7 months (CI95% 8-16) and median OS was 53.9 months (CI95% 34-73). 10 (13.6%) pts had T-DM1 discontinued due to only limiting toxicity and had no disease progression or death for at least 12 months. In this specific subgroup, 2 pts received T-DM1 as first line, 6 pts as second line, and 2 as third or more lines. At the start of T-DM1, 5 pts had visceral metastasis (3 liver, 2 lung), and 2 had only leptomeningeal involvement. Median age was 57 years (IQR 49-70) and median T-DM1 duration was 30 months (IQR 12-45). At the time of T-DM1 discontinuation, 9 pts presented complete response (CR) and 1 presented partial response (PR). 5 pts maintained CR, with no evidence of disease progression or death throughout the analyzed period. The PFS of these 5 pts, from the time of T-DM1 discontinuation to the last evaluation, was 35.6, 37.9, 40.5, 42.7 and 68.5 months. In the entire subgroup, median PFS was 22.5 months, 5-year OS was 66.7% and median OS was not reached. The adverse events that led to the T-DM1 discontinuation were thrombocytopenia (10%), nausea, vomiting and fatigue (10%), pneumonitis (20%), hepatic pseudocirrhosis (20%) and peripheral neuropathy (40%). Conclusions: Our experience suggests that pts with HER2-positive MBC who had T-DM1 discontinued due to limiting toxicity may derive long-term benefit. Further prospective studies are warranted to evaluate our findings, also including other ADC.

Real world assessment of clinical benefit with consolidation durvalumab following chemoradiotherapy in stage III unresectable non-small cell lung cancer.

e18853 Background: The phase III PACIFIC trial compared the efficacy of consolidation durvalumab to placebo in newly diagnosed, unresectable stage III non-small cell lung cancer (NSCLC) who had not progressed after chemoradiotherapy (CRT). With a median follow-up of 34.2 months, the median progression free survival (PFS) was 16.9 months (13.0-23.9) compared to 5.6 months (4.6-7.7) for placebo (HR = 0.55, 95% CI,0.45-0.68). We report a real-world study that utilizes surrogate endpoints to assess duration of clinical benefit with consolidation durvalumab. Methods: OncoHealth, a digital health company, conducted a retrospective observational real-world study to assess time to treatment failure in patients with unresectable Stage III NSCLC who received consolidation durvalumab after completion of CRT between June 2018-June 2021. Data sources included electronic medical records (EMR) submitted with prior authorization (PA) requests to OncoHealth and medical claims data. With a data cut-off of 12/22/2022, real-world Time to Progression (rwTTP), and real-world Time to Next Treatment (rwTTNT) were evaluated to assess time to treatment failure. All end points were measured from durvalumab administration dates, rwTTP spanned until earliest date of clinician-assessed progression, and rwTTNT spanned until initiation of subsequent treatment. Results: Total of 281 patients with unresectable Stage III NSCLC who received durvalumab after completion of definitive CRT were identified. Median age was 71 years (range: 53 to 88), 57% male, 53% former smokers, 47% Stage IIIA, 52% non-squamous histology and 98% received concomitant platinum-based chemotherapy prior to durvalumab. Median time between completing CRT and initiating durvalumab was 41 days. With a cutoff date of 12/22/2022, and a median follow up of 28.4 months, 34% (n = 95) experienced disease progression. Sites of progression included lung, lymph nodes, adrenal, liver, bone and brain. The median rwTTP was 10.6 months (range: 2.0-38.1 months) and median rwTTNT was 12.4 months (range: 2.5-39.6 months). Conclusions: In this real-world study, the patient and disease characteristics available in EMR were comparable to those reported in the PACIFIC trial. The rwTTP and rwTTNT reported here suggest treatment failure occurred within one year of exposure to durvalumab and subsequent line of treatment was initiated shortly thereafter. Variables such as co-morbidities, performance status, treatment compliance, change of payers and barriers to treatment in real world will be further explored.

Updated analysis of real-world treatment outcomes of first-line axitinib plus pembrolizumab in patients with advanced renal cell carcinoma in the United States.

e16553 Background: The combination of axitinib plus pembrolizumab (AXI+PEM) is a standard of care in the first-line (1L) treatment of patients with advanced clear cell renal cell carcinoma (ccRCC). Previous analyses described the demographic and clinical characteristics, as well as outcomes of patients receiving 1L AXI+PEM in a real-world setting. We report updated data with longer follow-up for this cohort. Methods: Electronic medical record data from the Flatiron Health, nationwide de-identified Database (280 cancer clinics across 800 sites in the US) were used to select patients with confirmed Stage IV/metastatic RCC and who initiated 1L AXI+PEM on or after 1/1/2018 to 7/31/2022. Analyses included best overall response to 1L therapy; real-world progression-free survival (rwPFS) and overall survival (rwOS) are reported as patients without a clinical event (rwPFS; progression/death; rwOS; death) at landmark time periods (3, 6, 9, 12, 18 and 24 months); denominators include censored patients. Other data are reported as medians (min, max) unless otherwise noted. Results: Three hundred and forty patients received 1L AXI+PEM, with an extended mean follow-up of 19.2 (0.1–41.6) months. Most patients were male (69.1%) and mean age of 64.1 (21.0–83.0) years. At diagnosis, 56.5% of patients had Stage IV RCC and 78.2% of patients had clear cell histology. IMDC Risk Score was favorable, intermediate, and poor in 24 (6.8%), 123 (34.4%), and 78 (22.1%) patients, respectively (unknown = 125 (36.8%)). At the time of analysis, 192 patients (56.5%) received only 1L therapy with AXI+PEM, while 148 patients (43.5%) received ≥1 subsequent line of treatment. Vascular endothelial growth factor receptor (VEGF-R) inhibitors were the most commonly used second-line (2L) treatment (109 patients, 73.6%), with cabozantinib being the most frequently used VEGF-R inhibitor (84 patients, 77.1%). Median rwPFS was 8.6 (CI: 7.2-9.7) months with 15.0% of patients achieving rwPFS at 2 years. Median rwOS was 29.4 (CI: 24.2-37.3) months with 38.5% of patients alive at 2 years. Best overall response rate to 1L was 54.1% (complete or partial response observed in 184/340 patients). 51.5% of patients required a dose hold, of which 58.3% required it due to an adverse event. Conclusions: This updated analysis supports the use of 1L AXI+PEM in patients with advanced RCC across all IMDC risk groups, providing further understanding of the clinical outcomes and treatment patterns of patients with advanced RCC in the US. [Table: see text]

Evaluating racial disparities for patients with advanced hepatocellular carcinoma (HCC) receiving first line immunotherapy within an equal access system.

4109 Background: The incidence and mortality of HCC are increasing in the USA. HCC disparities have been reported across the entirety of the cancer timeline, from screening to local and systemic treatment and liver transplant. We aim to analyze the clinical characteristics, outcomes, and racial disparities in patients with advanced HCC receiving first-line Atezolizumab plus Bevacizumab (A+B) in the Veterans Health Administration (VHA) – the only health care system in the USA that provides equal access to all patients. Methods: Patients were followed from their A+B initiation date through the earliest of the last VHA visit, loss to follow-up, death, or end of study on Jan 31, 2023. Structured electronic health record and chart review data were retrospectively collected to determine patient baseline characteristics, including self-reported race, number of A+B doses, treatment response, subsequent line of treatment, length of follow-up, and overall survival (OS). The Chi-Squared test was used to compare rates, and Mann-Whitney test was used to compare medians. Results: Three hundred twenty-five patients were included. 64% were non-Hispanic White (NHW), and 36% were all other (AO) ethnicities or races combined (26% Black, 8% Hispanic, 2% Asian or Indigenous). The median age for each cohort was similar (66 years for AO vs. 68 for NHW), and ECOG performance was &lt;1 in nearly 90% of each cohort. Viral hepatitis accounted for 70% and 48% of AO and NHW, respectively (p=0.0001). Despite clinical differences in OS and progression free survival (PFS), they were not statistically significant. Conclusions: Our VHA real-world data shows that despite having statistically significant etiologies, there was no statistically significant difference in the PFS and OS of patients with advanced HCC receiving first-line A+B in an equal access care system. This study supports our group’s findings in other malignant cohorts within VHA where equal healthcare access can mitigate other socio-demographic and biological factors. [Table: see text]