Received Second-line Treatment Research Articles

Real-world treatment patterns, resource utilization and costs in biliary tract cancers in the USA.

Aim: To evaluate real-world treatment patterns, survival and healthcare-resource utilization in US patients with advanced biliary tract cancers (BTC) receiving systemic therapy.Patients & methods: This study used claims data from the Healthcare Integrated Research Database (HIRD®) linked to clinical data from the Cancer Care Quality Program (January 1, 2015-September 30, 2020).Results: Of 413 patients, 84.5% received gemcitabine-based first-line (1L) treatment, 46% received second-line treatment, and 16.5% received third-line (3L) treatment. All-cause mortality was 53% and approximately 70% of patients had ≥1 inpatient visit. The total mean per-patient-per-month all-cause costs were $19,589 for 1L and $33,534 for 3L treatment.Conclusion: Results showed poor survival, significant resource use and high costs as treatment line progresses for patients with advanced BTC.

Long-term outcomes of sequential chemotherapy in epithelioid sarcoma

Our study was carried out to define the efficacy of treatment with sequential chemotherapy lines in patients with epithelioid sarcoma (ES) at referral centres for sarcoma. From 1998 to 2023, 22 patients with ES were treated with chemotherapy and included in the analysis. The median age at the start of palliative treatment was 35 (20–68). The median follow-up was 22.1 months. In the first line, 13 patients (59%) received anthracycline-based chemotherapy and 6 (27%) high-dose ifosfamide. One patient (4.5%) achieved PR, 15 (68%) SD, and 6 (32%) PD as the best response. The median progression-free survival (PFS) in the first line was 6.4 months (95% CI: 3.02–12.9), but 9.7 months (95% CI: 4.37–NR) for chemotherapy based on anthracycline, indicating a more favourable PFS (p = 0.027). Twenty (90%) patients received second-line treatment, and eleven received third-line chemotherapy. The median OS from the start of first-line palliative chemotherapy was 22.1 months (95% CI: 10.5–41.4) and 14.7 months from the beginning of the second line. Perioperatively, patients pretreated with anthracycline had a median PFS of 2.9 months in the M1 setting. Second-line long-time responses were achieved with pazopanib or vincristine with actinomycin D. Despite chemoresistance, an advantage associated with anthracycline-based chemotherapy was confirmed in the ES cohort. Poor responses underscore the need for further research on targeted therapies for ES. Second-line chemotherapy or clinical trials should be offered to all eligible patients.

Real-world efficacy of second-line therapies for Helicobacter pylori: a population-based study.

With the increasing prevalence of antibiotic resistance, real-world data on the optimal empirical second-line therapy for Helicobacter pylori are still limited. To evaluate the real-world efficacy of various second-line therapies for H. pylori. This was a retrospective population-based cohort study of all H. pylori-infected patients who had received the second-line treatment after the failure of primary clarithromycin triple therapy in Hong Kong between 2003 and 2018. The retreatment success rates of different second-line therapies were evaluated. A total of 7591 patients who received second-line treatment were included. Notably, the most commonly prescribed regimen was still clarithromycin triple therapy, but the frequency of use had decreased from 59.5% in 2003-06 to 28.7% in 2015-18. Concomitant non-bismuth quadruple therapy had emerged as the commonest regimen (from 3.3% to 43.9%). In a validation analysis, the sensitivity and specificity of retreatment-inferred second-line treatment failure were 88.3% and 97.1%, respectively. The overall success rate of second-line therapies was 73.6%. Bismuth quadruple therapy had the highest success rate of 85.6%, while clarithromycin triple therapy had the lowest success rate of 63.5%. Specifically, bismuth/metronidazole/tetracycline quadruple, metronidazole/tetracycline triple, levofloxacin/metronidazole/tetracycline quadruple, rifabutin/amoxicillin triple and amoxicillin/levofloxacin triple therapies had relatively higher success rates over 80%. Age, treatment duration, baseline conditions and first-line treatment used were associated with success rate. Bismuth quadruple therapy was the most effective second-line regimen for H. pylori in this real-world study. Despite a very low success rate, clarithromycin-containing triple therapies were still commonly used as second-line regimens.

A multicenter, retrospective study analysis: Evaluating the efficacy and safety of pembrolizumab in the first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma.

e18013 Background: PD-1-based therapy has become the first-line standard treatment for R/M HNSCC, but KN-048 lacked data on the mainland Chinese population. This study aims to conduct a pooled analysis of the efficacy and safety of first-line pembrolizumab-based therapy in patients (pts) with R/M HNSCC from different regions in China. Methods: Data comes from 17 hospitals. R/M HNSCC pts who received pembrolizumab alone or in combination with chemotherapy/targeted therapy from July 2020 to Jan 2023 were reviewed by searching the hospital HIS/medical record system. The primary endpoint of was OS, and secondary endpoints include time of pembrolizumab treatment (TOPT), safety, etc. Investigators also explored the impact of different biomarkers on survival. This study used SPSS 29 to analyze the data. Results: Total 160 pts were included. Median age was 60 yrs. 81.2% of pts was male, 95% of pts had an ECOG 0-1 . Main primary tumor site showed: oral cavity (60.6%), larynx (12.5%), oropharynx (10.6%). 88.8% of pts had undergone surgery in the past, and 65% received RT. The proportion of pts with only recurrence reached 75.6%. 79 (90.8%) had CPS of 1 or more and 44 (50.6%) had CPS of 20 or more. Other baseline information could be seen in the table. The median follow-up time was 18.5 mos. 70.6% of pts received pembrolizumab combined with chemotherapy, 17.5% received pembrolizumab alone. 48 pts subsequently received second-line treatment, more than half of which were target-based treatments. The median OS of all pts was not reach, among which the mono group vs. combination chemotherapy group (p=0.254). 18mo-OS of monotherapy was 69%, while 61% in combination. No statistical difference was seen in mTOPT (6.0 vs 4.7 mos, p=0.644). The results of the Cox Proportional Hazards Model suggest that ECOG score, smoking history, previous RT and distant metastatic of tumors were related to OS. Primary tumor location, T stage, EGFR mutation related to TOPT. Studies have not found a significant correlation between CPS and survival prognosis. 28.1% of pts experienced TRAEs, the most common of which was G1-4 myelosuppression (33.3%). The main TRAEs of G3-4 were pneumonia (11.1%), bone marrow suppression (8.9%) and abnormal liver function (4.4%). No patient died due to TRAEs. Conclusions: The data reflects that the real-world mOS with local recurrence as the main population was significantly higher than KN-048, and some clinical indicators related to prognosis were also found. In the future, the data of pembrolizumab in R/M HNSCC will be further explored to find more valuable biomarkers. [Table: see text]

Treatment strategies and outcome in relapsed peripheral T-cell lymphoma: results from the Netherlands Cancer Registry

AbstractOptimal treatment in patients with refractory or relapsed peripheral T-cell lymphomas (R/R T-NHLs) is unknown. In this population-based study, outcomes in R/R peripheral T-cell lymphoma not otherwise specified (PTCL NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic lymphoma kinase-positive (ALK+) and ALK-negative (ALK–) anaplastic large cell lymphoma (ALCL) were evaluated. Patients with PTCL NOS, AITL, ALK+ ALCL, and ALK– ALCL (≥18 years) diagnosed in 2014 to 2019 were identified using the Netherlands Cancer Registry. End points were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The 2-year PFS of 821 patients was 57%. Among 311 patients with a relapse, 243 received second-line treatment: 44% received salvage chemotherapy, 20% received brentuximab vedotin (BV), and 36% received other treatment. In third-line treatment, BV was most commonly used (38%). ORR after second-line treatment was 47%. Two-year PFS and OS after relapse were 25% and 34%, respectively. The risk of second relapse was negatively affected by early relapse (<12 months after diagnosis), whereas BV reduced this risk compared with salvage chemotherapy. Reduced risk of relapse was independent of histological subtype. The best outcomes were observed for patients treated with salvage chemotherapy receiving consolidative autologous and allogeneic stem cell transplantation (SCT) (2-year OS 68%), patients treated with BV achieving a second complete remission (2-year OS 74%) and patients with allogeneic SCT (2-year OS 60%). The risk of second relapse was significantly lower for patients with R/R T-NHL treated with BV compared with patients treated with salvage chemotherapy, and this was irrespective of subtype. Therefore, the use of salvage chemotherapy for patients with R/R T-NHL is challenged.

Clinical features and treatment outcomes of liver involvement in paediatric Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder in children, and liver involvement in LCH is rare. This retrospective study reported the clinical features and prognosis of patients with hepatic LCH. Liver involvement was defined by histopathological findings, liver dysfunction or abnormalities, or ultrasound imaging. A total of 130 patients (14.5%) with hepatic LCH out of 899 in the LCH population were enrolled. Patients with liver involvement had greater frequencies of skin, lung, hearing system, and haematologic system involvement, and hemophagocytic lymphohistiocytosis (P<0.001, 0.001, 0.002, 0.009, and <0.001, respectively). Overall survival and progression-free survival were lower in LCH patients with liver involvement than in those without liver involvement (P<0.001 and <0.001). In patients with liver involvement, the overall survival (OS) and progression-free survival (PFS) rates were lower in patients with cholangitis than in those without cholangitis (P<0.020 and 0.030). For the treatment response, the response rate of hepatic LCH patients to initial first-line therapy (n=89) was 22.5%. However, there was no significant difference in the response rate or recurrence rate between patients who shifted from first-line treatment to second-line treatment (n=29) or to targeted therapy (n=13) (P=0.453 and 1.000). The response rate of hepatic LCH patients who received initial second-line therapy (n=13) was 38.5%. Two of these patients subsequently experienced bone recurrence. The response rate of hepatic LCH patients who received initial targeted therapy (n=16) was 75.0%. Three patients subsequently experienced recurrence, including 2 in the bone and 1 in the liver and skin. A total of 39.3% of patients who received second-line treatment had severe myelosuppression (grade III-IV), and 50.8% had varying degrees of gastrointestinal events, whereas there was no severe toxicity in patients who received first-line treatment and targeted therapy. Four patients underwent liver transplantation because of liver cirrhosis. The patients’ liver disease improved within a follow-up period of 18-79 months. This study demonstrated that LCH with liver involvement, especially cholangitis, indicates a poor prognosis. Targeted therapy provides a good treatment response and less toxicity. However, it may relapse after withdrawal. Liver transplantation is still a reliable salvage option for patients with end-stage liver disease.

Treatment Patterns and Attrition With Lines of Therapy for Advanced Urothelial Carcinoma in the US

The treatment paradigm for advanced urothelial carcinoma (aUC) has undergone substantial transformation due to the introduction of effective, novel therapeutic agents. However, outcomes remain poor, and little is known about current treatment approaches and attrition rates for patients with aUC. To delineate evolving treatment patterns and attrition rates in patients with aUC using a US-based patient-level sample. This retrospective cohort study used patient-level data from the nationwide deidentified electronic health record database Flatiron Health, originating from approximately 280 oncology clinics across the US. Patients included in the analysis received treatment for metastatic or local aUC at a participating site from January 1, 2011, to January 31, 2023. Patients receiving treatment for 2 or more different types of cancer or participating in clinical trials were excluded from the analysis. Frequencies and percentages were used to summarize the (1) treatment received in each line (cisplatin-based regimens, carboplatin-based regimens, programmed cell death 1 and/or programmed cell death ligand 1 [PD-1/PD-L1] inhibitors, single-agent nonplatinum chemotherapy, enfortumab vedotin, erdafitinib, sacituzumab govitecan, or others) and (2) attrition of patients with each line of therapy, defined as the percentage of patients not progressing to the next line. Of the 12 157 patients within the dataset, 7260 met the eligibility criteria and were included in the analysis (5364 [73.9%] men; median age at the start of first-line treatment, 73 [IQR, 66-80] years). All patients commenced first-line treatment; of these, only 2714 (37.4%) progressed to receive second-line treatment, and 857 (11.8%) advanced to third-line treatment. The primary regimens used as first-line treatment contained carboplatin (2241 [30.9%]), followed by PD-1/PD-L1 inhibitors (2174 [29.9%]). The PD-1/PD-L1 inhibitors emerged as the predominant choice in the second- and third-line (1412 of 2714 [52.0%] and 258 of 857 [30.1%], respectively) treatments. From 2019 onward, novel therapeutic agents were increasingly used in second- and third-line treatments, including enfortumab vedotin (219 of 2714 [8.1%] and 159 of 857 [18.6%], respectively), erdafitinib (39 of 2714 [1.4%] and 28 of 857 [3.3%], respectively), and sacituzumab govitecan (14 of 2714 [0.5%] and 34 of 857 [4.0%], respectively). The findings of this cohort study suggest that approximately two-thirds of patients with aUC did not receive second-line treatment. Most first-line treatments do not include cisplatin-based regimens and instead incorporate carboplatin- or PD-1/PD-L1 inhibitor-based therapies. These data warrant the provision of more effective and tolerable first-line treatments for patients with aUC.

Abstract PO1-04-05: Effectiveness and safety of inetetamab + pyrotinib + vinorelbine in ≥second-line treatment of HER2-positive metastatic breast cancer

Abstract Background: In real-world settings, Patients with HER2-positive metastatic breast cancer (MBC) who cannot receive antibody-drug conjugates (ADCs) as standard second-line therapy due to cost–benefit ratios and who have no preferred options as ≥third-line regimen by NCCN guidelines, require new regimens to meet their clinical needs. This study aims to explore the effectiveness and safety of inetetamab + pyrotinib + vinorelbine for ≥second-line treatment of HER2-positive MBC. Methods: Patients with HER2-positive MBC who received ≥second-line treatment at our hospital from June 2020 to December 2022 were enrolled. Progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR) and adverse reactions were assessed. Patients received inetetamab + pyrotinib + vinorelbine until disease progression or unacceptable toxicity were evaluated every two cycles according to the RECIST 1.1 criteria. Results: 89 patients were included based on the inclusion and exclusion criteria. Among them, 45 patients received second-line treatment who couldn't use T-DM1 or T-DXd, and 44 patients received ≥third-line treatment. The median PFS of the second-line treatment subgroup was 17months, the ORR and CBR were 60.0% and 86.7%, respectively, which were significantly higher than those in the ≥third-line treatment subgroup and numerically superior to T-DM1 as a second-line treatment option. Additionally, the ORR and CBR of patients with baseline brain metastasis who did not receive radiotherapy were 27.3% and 72.7%, respectively. The most common adverse events observed were leukopenia (37.1%), neutropenia (42.7%), anemia (34.8%) and diarrhea (67.4%). The incidence of grade 3-4 leukopenia, neutropenia, anemia and diarrhea were 11.2%, 15.7%, 55.6% and 27.0%, respectively. A total of 8 patients (8.9%) discontinued medication due to adverse reactions. Conclusions: Inetetamab + pyrotinib + vinorelbine demonstrates good efficacy and controllable toxicity as a second-line treatment for HER2-positive MBC. This therapeutic regimen provides a viable alternative option for patients who are unable to receive ADCs as the second-line treatment. Citation Format: Fan Wu, Mulan Chen, Weiwei Huang, Lili Wang, Nani Li, Xiufeng Wu, Xinhua Chen, Yi Hong, Lin Lin, Kan Chen, Jian liu. Effectiveness and safety of inetetamab + pyrotinib + vinorelbine in ≥second-line treatment of HER2-positive metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-04-05.

Active tuberculosis incidence among treatment failure experienced patients in North Wollow Zone: A multicenter historical cohort.

In Ethiopia, tuberculosis (TB) is a significant cause of death among individuals living with HIV, especially in resource-limited areas and those who have experienced treatment failure. However, there is the paucity of data regarding TB among treatment failures experienced people living with HIV. This study aimed to estimate the rate and identify predictors of tuberculosis among patients who received second-line treatment in North Wollo, Northeast Ethiopia. A retrospective follow-up study was conducted on 474 HIV-infected patients who experienced treatment failure. The study period ranged from January 2015 to September 30, 2021. The incidence of TB was assessed using a Cox proportional hazard regression model, after ensuring that all assumptions were met. Factors associated with active TB were determined by analyzing adjusted hazard ratios and 95% confidence intervals. In a study of 474 HIV-positive patients on second-line antiretroviral treatment, we found an incidence rate of 3.6% with 17 new cases of TB observed over 4412.4 persons per year (PPY). The overall incidence density rate was estimated to be 0.39 cases per 100 PPY (95% CI: 0.239-0.618). Regarding the occurrence of active TB in second-line patients, WHO clinical treatment stage (T3 and T4), missed isoniazid preventive therapy had a significantly higher risk (AHR: 13.225, 95% CI: 2.894-60.434, p = 0.001), while being married was associated with a lower risk (AHR: 0.203, 95% CI: 0.045-0.907, p = 0.001). A high incidence of active TB was observed shortly after initiating second-line antiretroviral treatment. Factors such as being in the WHO clinical treatment stage (T3 and T4) and marital status were determinants for active TB. To improve overall survival rates, it is vital to enhance early TB screening and implement effective isoniazid preventive therapy.

Survival impact of sequential chemotherapy following pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma.

Pembrolizumab alone or combined with chemotherapy is the standard of care for first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) with positive programmed death-ligand 1 combined positive scores. However, data on second-line chemotherapy following pembrolizumab are scarce. A single-center, retrospective study was conducted to determine the efficacies of pembrolizumab and pembrolizumab plus chemotherapy as first-line treatments and the efficacy of second-line chemotherapy for patients with R/M HNSCC who were refractory or intolerant to first-line treatment. Fifty-four patients were treated with pembrolizumab, and 29 received second-line therapy, with 27 opting for cetuximab-containing regimens. The median progression-free survival (PFS), overall survival (OS), and PFS on next-line therapy for first-line treatment were 4.7 (95% confidence interval [CI], 2.1-8.7), 22.1 (95% CI, 12.6-not reached), and 15.6months (95% CI, 9.7-not reached) in the pembrolizumab group and 5.4 (95% CI, 3.3-6.8), 15.8 (95% CI, 8.6-not reached), and 13.7months (95% CI, 8.1-not reached) in the pembrolizumab plus chemotherapy group, respectively. The overall response rate and median PFS for second-line treatment were 48.3% (95% CI, 30.4-67.0) and 6.1months (95% CI, 2.30-8.84). The median OS for patients who received second-line treatment was 18.4months, which was superior to the median OS of 6.0months for patients who received the best supportive care (log-rank p = 0.10). This study indicates that cetuximab-containing second-line chemotherapy can improve outcomes in R/M HNSCC, even after first-line therapy failure or intolerance.

Osimertinib in Patients With Treatment-Naive EGFR-Mutant Non-small Cell Lung Cancer: Overall Survival, Post-progression Management and Budget Impact Analysis in Real-World.

The observational multicenter prospective FLOWER study (NCT04965701) confirmed effectiveness and safety of osimertinib in the real-world (RW) management of untreated EGFR-mutant advanced non-small cell lung cancer (aNSCLC) patients. Herein, we report updated survival data, post-progression management, cost/effectiveness and budget impact (BI) of osimertinib compared with a RW population receiving gefitinib or erlotinib. Overall, 189 Caucasian patients receiving first-line osimertinib were included. After a follow-up of 20.7 months, 74(39.2%) patients discontinued osimertinib, median time-to-treatment discontinuation (mTTD) was 27.9 months, overall survival 36.8 months. At progression, tissue biopsy was performed in 29 (56.9%), liquid biopsy in 15 (29.4%) and both in 7 (13.7%) cases. The most frequent resistant mechanism was MET amplification (N = 14, 29.8%). At data cutoff, 13 (6.9%) patients were continuing osimertinib beyond progression; 52 (67.5%) received second-line treatment; no further treatments were administered in 25 (32.5%) cases. Thirty-three (63.4%) patients received chemotherapy, 12(23.1%) TKIs combination. Cost-effectiveness analysis showed a total cost per patient based on RW mTTD of 98,957.34€, 21,726.28€ and 19,637.83€ for osimertinib, erlotinib and gefitinib, respectively. The incremental cost-effectiveness ratio (ICER)/month for osimertinib was 359,806.0€/life-year-gained (LYG) and 197,789.77€/LYG compared to erlotinib and gefitinib. For osimertinib, the BI-gap between RW-TTD and theoretical-TTD was 16,501.0€ per patient. This updated analysis confirms the effectiveness of osimertinib in RW. Although the ICER of osimertinib seems not cost-effective, additional costs for the management of disease progression to old generation TKIs were not considered in this study. The BI-gap suggests RW mTTD as a more reliable measure for expense estimation.

Real-world epidemiology and treatment patterns of patients with locally advanced or metastatic urothelial carcinoma: Retrospective analysis of Diagnosis Procedure Combination claims data in Japan.

Evaluate real-world epidemiologic trends and treatment patterns in newly diagnosed patients with locally advanced or metastatic urothelial carcinoma (la/mUC) in Japan. This retrospective analysis included adults with newly diagnosed la/mUC in Japan (January 2015-December 2019) from a nationwide-linked electronic medical record Diagnostic Procedure Combination claims dataset. Outcomes included epidemiologic trends (incidence and prevalence), baseline demographics, clinical characteristics, and treatment patterns in newly diagnosed patients with la/mUC before (2015-2017) and after (2018-2019) approval of pembrolizumab in Japan. Of 975 patients included, 76.4% were men; 71.6% were aged 70 years or older. Most cases (70.5%) were of the bladder. Between 2015 and 2019, the annual age-adjusted incidence increased from 6.8 to 12.4 per 100 000; the annual age-adjusted period prevalence increased from 13.0 to 25.2 per 100 000; and 307 (31.5%) and 668 (68.5%) patients were diagnosed from 2015 to 2017 and 2018 to 2019, respectively. Overall, 731 (75%) patients received systemic anticancer therapy; all received 1 line and 50.2% received 2 lines of therapy; 78.3% of patients received gemcitabine plus platinum-based therapy and 2.2% received pembrolizumab as first-line treatment. First-line treatment rates increased from 69.4% to 77.5% after pembrolizumab approval. Of 367 patients who received second-line treatment, 22.3% received gemcitabine plus platinum-based therapy; 14.7% received pembrolizumab. In the Japanese regions considered, incidence and prevalence of newly diagnosed la/mUC increased over time and first-line treatment with pembrolizumab increased after approval.

A nationwide analysis of the treatment patterns, survival, and medical costs in Korean patients with relapsed or refractory diffuse large B-cell lymphoma.

Approximately one-third of patients with diffuse large B-cell lymphoma (DLBCL) are refractory to treatment or experience relapse after initial therapy. Unfortunately, treatment options for older patients and those who experience relapse or become refractory to hematopoietic stem cell transplantation (HSCT) are limited. This nationwide population-based study aimed to identify treatment patterns, survival times, and treatment costs in patients with relapsed/refractory DLBCL (R/R DLBCL). Between 2011 and 2020, data on patients with R/R DLBCL were retrieved from the Korean Health Insurance Review & Assessment Service, encompassing the entire population. We identified the treatment patterns for each treatment line using a Sankey diagram and calculated the median time to the subsequent treatment in line. Median overall and progression-free survival times were estimated using the Kaplan-Meier survival curves. Finally, the medical costs incurred during DLBCL treatment were calculated for each treatment line and the costs related to HSCT were summarized at the episode level. A total of 864 patients with R/R DLBCL who received second-line treatment were identified, and a regimen of ifosfamide, carboplatin, and etoposide (ICE) was administered the most. Among them, 353 were refractory or relapsed cases that were treated with third-line treatments. The median times for second-line to third-line, third-line to fourth-line, fourth-line to fifth-line, and fifth-line to sixth-line treatment failures gradually decreased (3.93, 2.86, 1.81, and 1.38 months, respectively). The median overall survival time was 8.90 and 4.73 months following the second-line and third-line treatments, respectively. In the third-line treatment setting, the patients did not show a significant difference in survival time after HSCT. The median medical cost was $39,491 across all treatment lines including the cost of HSCT which was $22,054. The treatment patterns in patients with R/R DLBCL, especially at third-line treatments and thereafter, were complicated, and their prognosis was poor despite the high medical costs. Novel and effective treatment options are expected to improve the prognosis and alleviate the economic burden of patients with R/R DLBCL.

Treatment options and outcome of patients with metastatic renal cell carcinoma with brain or bone metastases: Real world evidence from a German retrospective multi-center analysis.

387 Background: Brain (BM) and bone metastases (BOM) in renal cell carcinoma (RCC) are associated with poor outcome. We evaluated real-world treatment paradigms of RCC patients with BM and BOM. Methods: We retrospectively analyzed RCC patients with BM and/or BOM treated at 18 German tertiary cancer centres from 2003 to 2023. Adverse events (AE) were reported according to CTCAE 5.0, objective response rate (ORR) according to local standard. Overall survival (OS) was calculated from start of treatment to progression or death, respectively and determined by KM plots. Results: We included 453 patients with a median age of 64 years (IQR 56-71). 93% of all patients had BOM, 15% BM and 8% both. Most patients (79%) had clear cell RCC, 7% of all patients had sarcomatoid differentiation. 82% of patients had an ECOG PS of 0/1. IMDC risk was favorable/intermediate/poor in 20/56/24%. 64% received prior nephrectomy. Patients with BOM received first-line IO-combinations in 61% (IO-IO: 38%, TKI-IO: 62%), TKI-monotherapy in 39%, while patients with BM received IO-combinations in 68% (IO-IO: 37%, TKI-IO: 63%) and TKI in 32%. IO-based first-line therapy increased from 2003 to 2023. AE of all grades occurred in 87% and 69% during IO-based therapy or TKI monotherapy, and CTCAE grade ≥ 3 in 42% or 25%. Best ORR and survival outcomes with median follow-up of 23 months (IQR 9-42) are described in table 1. 56% and 58% of all patients with BOM and BM received second-line treatment, with Cabozantinib (34%; 34%) and Nivolumab (17%, 23%) being the most common treatment options. In the subgroup of RCC with sarcomatoid features (n=36), 34 patients had BOM and 7 had BM, of which were treated with IO-combinations in 88% (BOM; IO-IO: 41%, TKI-IO: 59%) or 66% (BM; IO-IO: 50%, TKI-IO: 50%) and TKI-monotherapy in 12% (BOM) or 34% (BM) of all patients. Response rates (ORR/SD/PD) were 48%/28%/24% for IO-based therapy and 0%/50%/50% for TKI-monotherapy in RCC with sarcomatoid features, mOS was 41 months (95% CI 16.7-65.3). Conclusions: RCC patients with BOM and BM are increasingly treated with IO-combinations but lead to higher rates of AE grade ≥ 3. In patients with BOM, IO-TKI revealed higher ORR compared to IO-IO combination, but not in patients with BM. However, the small sample size and retrospective design are major limitations of our analysis. Prospective studies evaluating treatment options for BOM and BM in patients with RCC is critical. [Table: see text]

A retrospective analysis of prognostic factors and treatment choices in small cell lung cancer with liver metastasis.

Small cell lung cancer (SCLC) is characterized by high aggressiveness and early dissemination, with the liver being the most common site of metastasis. Although it has been established that the prognosis for SCLC with liver metastasis is exceedingly poor, comprehensive data on clinical features, prognostic factors, treatment options, and outcomes of this patient population remain limited. This retrospective study aims to examine the clinicopathological features and current treatment landscape and to identify prognostic factors associated with SCLC with liver metastasis in real-world settings. We conducted a retrospective analysis of data on SCLC patients with liver metastasis at initial diagnosis between January 1, 2013, and January 1, 2022. Kaplan-Meier analysis and log-rank tests were employed to estimate the overall survival (OS) and progression-free survival (PFS). Cox regression models were utilized to identify independent prognostic factors. A total of 349 patients were included in the study, with 97.7% of patients exhibiting pure SCLC and 42.4% of patients presenting with concomitant bone metastasis. Approximately one-fourth of the patients had metastases in ≥3 organs, and 18.9% of patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2. The median OS was 10.97 months (95% CI: 9.88-12.06) for those who received first-line therapy (n=286). Of these, 263 patients were treated with chemotherapy, showing a median OS of 11.37 months. Furthermore, 43.8% of patients received second-line treatment, and 81 patients proceeded to third-line treatment. ECOG PS ≥2 and mixed-SCLC were identified as independent adverse prognostic factors in SCLC with liver metastasis, whereas treatments including systemic treatment alone or in combination with local radiotherapy were associated with better prognoses. This retrospective study substantiated that ECOG PS ≥2 and mixed SCLC are independent predictors of poor prognosis for SCLC with liver metastasis. Additionally, different treatment strategies can improve the survival of this patient population, with chemotherapy currently being the main treatment option.

Efficacy and safety of regorafenib in combination with immune checkpoint inhibitor therapy as second-line and third-line regimen for patients with advanced hepatocellular carcinoma: a retrospective study.

Despite the emergence of immune checkpoint inhibitors (ICIs) as first-line treatment for advanced hepatocellular carcinoma (HCC), there is an unmet need regarding subsequent treatments in patients that fail ICI. Regorafenib is a vascular endothelial growth factor receptor (VEGFR) inhibitor, which could increase programmed death-ligand 1 (PD-L1) expression in tumors and increase intra-tumoral CD8+ T-cell infiltration by normalizing the cancer vasculature and improving the efficacy of the programmed cell death protein 1 (PD-1) antibody. Thus, we evaluated the combination of regorafenib and a PD-1 inhibitor for advanced HCC patients that had failed combined tyrosine kinase inhibitors (TKIs) plus ICI. Data of patients with advanced HCC who had failed combined TKIs plus ICI treatment and were afterwards treated with combined regorafenib plus a PD-1 inhibitor were reviewed. All patients had received PD-1 inhibitors as part of the first-line treatment and regorafenib every 4 weeks until disease progression, intolerable toxicities, or physician/patient withdrawal. The clinical data, previous treatment strategies, follow-up imaging results, and adverse events (AEs) during follow-ups were recorded. Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0 was used to evaluate AEs and Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 was used to evaluate response. The primary endpoint was safety, and the secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and duration of response (DOR). From November 15, 2020, to January 31, 2022, data of 17 patients with advanced HCC that met the criteria were reviewed. The cohort included 16 men and 1 woman with a median age of 54 years (interquartile range, 46 to 63 years). Sixteen patients had Child-Pugh class A (n=16, 94.12%) and one with class B (n=1, 15.9%) liver disease. Thirteen patients received second-line treatment, and the remaining patients received third-line treatment. All patients received at least 1 dose of PD-1 inhibitors. The median follow-up duration was 7.62 months. Twelve recipients experienced treatment-related AEs. The most frequent AE (≥5%) included fatigue (17.64%), diarrhea (17.65%), proteinuria (5.88%), bleeding gums (11.76%), and hypertension (11.76%). No grade-4 AE or new safety signals were identified. The ORR and DCR were 41.2% and 64.7%, respectively, and the median PFS was 5.09 months. Regorafenib combined with PD-1 inhibitor is a promising regimen in treating patients with advanced HCC owing to its safety and effectiveness as well as low incidence of serious AEs with its use.

Treatment Patterns and Real-World Outcomes for Locally Advanced or Metastatic Urothelial Cancer in the Era of Immunotherapy

Background and objectiveThere are limited data on real-world outcomes for patients with advanced or metastatic urothelial cancer (mUC) since immune checkpoint inhibitors (ICIs) became available. Our objective was to analyze outcomes for patients with mUC since ICIs became available. MethodsWe performed a retrospective analysis of 131 patients with mUC attending the outpatient clinic of a single tertiary care center who received systemic therapy between June 2017 and July 2021 with follow-up up to December 2022. Summary and descriptive statistics were calculated for categorical and continuous variables. The Kaplan-Meier method was applied to calculate survival, and a Cox proportional-hazards model was used to explore associations between clinical variables and outcomes. Key findings and limitationsThe median patient age was 68 yr (range 35–90). The first systemic therapy administered was platinum-based in 79% of cases and ICI-based in 21%. Some 61% of the cohort received a second systemic treatment, with 75% of these an ICI. Median overall survival for the entire cohort was 24 mo (interquartile range 9–35). Patients on ICI therapy for ≥6 mo had median overall survival of 59 mo (95% confidence interval 39 mo–not reached). Metastatic sites on initiation of ICI therapy and C-reactive protein kinetics were prognostic in patients receiving ICIs. Limitations include the retrospective design and inherent selection bias. Conclusions and clinical implicationsMore than 60% of patients with mUC received second-line treatment, and 75% of these received an ICI. Patients staying on immunotherapy for more than 6 mo have substantially better outcomes in comparison to patients with less time on immunotherapy and historical cohorts. Patient summaryWe looked at the lines of therapy and outcomes for patients with advanced or metastatic cancer of the urinary tract, starting from when immunotherapy drugs called immune checkpoint inhibitors (ICIs) became available. We found that 60% of patients have received second-line therapy, which is a double the rate in comparison to historical groups of patients. Patients with long-term ICI therapy (>6 months) had significantly better outcomes, with a median survival of more than 3 years.

Impact of Real-World Treatment Sequencing Patterns on Time to Next Treatment among Patients with Chronic Lymphocytic Leukemia in the United States

Background: The treatment landscape for chronic lymphocytic leukemia (CLL) is evolving at a rapid pace, with development of several targeted therapies. The real-world applicability of clinical trial effectiveness is markedly influenced by treatment choices, the specific characteristics of patients' diseases, their overall health, and individual preferences. However, there is limited evidence to understand the impact of multiple treatment options on real-world effectiveness in CLL in routine clinical practice. This study aimed to characterize recent real-world treatment sequencing patterns and associated time to next treatment among patients with CLL in the United States. Methods: This retrospective observational study included patients diagnosed with CLL (≥18 years at diagnosis) from January 1, 2018, through January 1, 2023, who received ≥1 treatment after initial diagnosis. Patients were sourced from the ConcertAI RWD360 dataset, a real-world de-identified dataset &amp;gt;6 million patients from across the United States derived from various electronic health record systems and integrated with a large administrative open claims dataset. Patients were followed through the end of the record or death, whichever occurred first. Patients were classified into the following treatment categories: chemotherapy (including bendamustine-based and other chemotherapy), anti-CD20-based, Bruton tyrosine kinase inhibitor (BTKi)-based (ibrutinib, acalabrutinib, or zanubrutinib), and venetoclax-based therapy. Demographic and clinical characteristics, treatment sequencing pattern, and time to next treatment were examined across lines of therapy for each treatment category. Kaplan-Meier analysis was used to estimate median time to next treatment. Results: The study included 3,431 patients with CLL (median age: 69 years; male: 63.8%). There was a significant variation in average age among the 4 treatment groups ( P&amp;lt;0.0001). Compared with the overall population, patients who received anti-CD20-based therapy were slightly older (median age: 71 years), while patients who received venetoclax-based therapy were relatively younger (median age: 67 years). Patients were primarily treated in community rather than academic settings (76.4% vs 21.3%). First-line patients were most commonly treated with BTKi (60.1%), venetoclax (16.0%), and anti-CD20 (15.4%) regimens. Among patients who initiated BTKi therapies, zanubrutinib use (2.6%) was limited; this may be due to the recent approval date (January 2023). Among CLL patients, 35.0% received second-line treatment and BTKi stayed dominant (35.7%), followed by anti-CD20 (29.6%) and venetoclax (25.8%) therapies. From first- to second-line therapy, the prevailing sequencing pattern was from either one BTKi to another BTKi (23.5%), venetoclax to anti-CD20 (13.2%), or BTKi to an anti-CD20 (9.7%). From second- to third-line therapy, patients most frequently switched from anti-CD20 to venetoclax (24.6%), anti-CD20 to BTKi (13.3%), or one BTKi to another BTKi (12.6%). From third- to fourth-line therapy, the predominant sequencing pattern was from venetoclax to anti-CD20 (21.3%), anti-CD20 back to venetoclax (20.6%), or one BTKi to another BTKi (11.6%). Median time to next treatment in first line was significantly longest for patients receiving BTKi (53.9 months) and shortest for patients treated with venetoclax (7.7 months) ( P&amp;lt;0.0001) (Figure 1). Median time to next treatment in second line was not reached among patients using BTKi, while it was significantly shorter for those on venetoclax and anti-CD20 (10.4 months and 1.5 months, respectively; P&amp;lt;0.0001) (Figure 2). Conclusions: This studydemonstrated unique treatment sequencing patterns among patients with CLL in the real-world setting.As the most commonly used regimen, BTKi therapy was shown to have significantly improved time to next treatment compared with other treatment regimens in first and second lines of therapies. Future studies with extended follow-up are needed to allow for assessment of newer treatments and enable evaluation of long-term clinical outcomes.

Trametinib Maintenance in Patients with RAS Mutated Hematologic Malignancy Undergoing Allogeneic Haematopoietic Stem-Cell Transplantation: A Retrospective Transplant Study

Aim: The abnormal activation of MAPK signaling pathway plays an important role in the occurrence and development of leukemia. Whether MEK inhibitors can effectively reduce the recurrence of hematologic malignancy, We reviewed the efficacy and safety of trametinib maintenance in post-transplant patients with RAS mutations. Methods: Our study retrospectively analyzed 61 hematologic malignities with RAS mutation who underwent allo-HSCT at Beijing Gaobo Boren Hospital between January 2018 and January 2023. Twenty-five patients received maintenance therapy with trametinib post-HSCT(trametinib group), and 36 patients did not receive any maintenance therapy (control group). Trametinib group and control group also achieved CR at 2 months post-HSCT. Results: The diagnosed including AML (23, 37.7%), B-ALL (33, 54.1%), T-ALL (3, 5.0%), and 2 others (3.3%). Male: female = 29:32, The median age was 15 (1-68) years old. Before transplantation, 5 patients (8.2%) had extramedullary lesions and 16 patients (26.2%) had chromosomal abnormalities. The disease status before transplant was CR (42,68.9%),PR(6,9.7%),NR (13,21.3%) . 53 patients (86.9%) received second-line treatment. Fifteen cases (24.6%) were secondary transplants. Donor type included haploidential (45, 73.8%), identical sibling (5, 8.2%), and unrelated (11, 18.0%). Myeloablative conditioning regimen with eitherTBI/fludarabine (33, 54.1%) based or busulfan/fludarabine (28, 45.9%) based were applied. There were no significant differences between the two groups in age, sex, extramedullary disease,central nervous leukemia, karyotype analysis, disease status, conditioning regimen, donor type,acute and chronic GVHD and acute GVHD grades. The median follow-up time was 16.5 months (95%CI: 16.8-24.8 months), and the overall survival(OS) was 81.2% (95%CI: 68.6-89.1%). The disease-free survival (PFS) was 73.0% (95%CI: 59.7-82.5%). Trametinib group, the OS was 91.5% (95%CI: 70.0-97.8%), PFS was 88.0% (95%CI: 67.3-96.0%). Control group, the OS was 73.9% (95%CI: 55.9-85.6%), PFS was 65.8% (95%CI: 47.7-78.9%). Trametinib significantly improved the OS and DFS (P=0.044; P=0.041). In the trametinib group, 4 patients died after treatment, of which 3 died of relapse and 1 died of respiratory failure. In the non-trametinib group, 13 patients died, of which 6 died of relapse and 7 died of infection, stroke, GVHD and other causes. Trametinib treatment was initiated at a median of 94 days (range 63-178) at a median dose of 1 (range 0.5-2) mg daily.Trametinib was temporarily discontinued in 9 patients and dose modification in 12 patients because of side effects. mainly due to side effects including hematotoxicity in 5 patients, nosebleed in 4 patients, diarrhea in 1 patient, fatigue in 1 patient, and disease recurrence in 1 patient. The median modified daily dose was 0.5mg (range 0-1mg). Grade 2 AES occurred during the course of trametinib treatment, and no ≥ grade 3 AES was observed. The most common adverse events were neutropenia, anemia, thrombocytopenia, epistaxis, neutropenic fever, and fatigue, all of which were tolerable and reversible. No cardiorespiratory, renal, or neurotoxicity, or treatment-related deaths were observed. The median duration of trametinib maintenance therapy was 270 days (range 30-630 days). Conclusions: In this study, We have observed that trametinib maintenance post-transplantation can significantly improve the prognosis of patients with RAS mutations.Trametinib can be used as maintenance therapy with different conditioning regiments post-HSCT, which does not increase the risk of GVHD and organ injury, and is safe and effective. Future prospective clinical trials with larger sample sizes are needed for further research.

Postinfusion Monitoring Health Care Resource Utilization and Costs By Site of Care Among Inpatients and Outpatients with Relapsed or Refractory Large B-Cell Lymphoma Who Received Second-Line Treatment with Lisocabtagene Maraleucel in the TRANSFORM and PILOT Clinical Trials

Background:CAR T cell therapy administration is often in an inpatient (IP) setting due to the possibility of severe AEs after infusion. Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, 4-1BB CAR T cell product administered at equal target doses of CD8 + andCD4 + CAR + T cells. Outpatient (OP) administration of liso-cel is feasible given trial-demonstrated low rates of grade ≥ 3 AEs that require hospitalization, including cytokine release syndrome and neurological events (Bachier CR, et al. J Clin Oncol 2020). Follow-up care in the OP setting may differ from that in an IP setting and may offer an opportunity to reduce AE management-related health care resource utilization (HCRU) and costs; limited data is published on this topic. Thus, this study assessed postinfusion monitoring HCRU and costs by site of care (ie, IP/OP) among patients with R/R large B-cell lymphoma (LBCL) treated with liso-cel as second-line (2L) therapy in TRANSFORM (NCT03575351) and PILOT (NCT03483103) clinical trials. Methods: A microcosting methodology was used to assess postinfusion monitoring-related HCRU identified from pooled TRANSFORM and PILOT case report forms and to estimate associated costs (excluding liso-cel acquisition costs) by site of care using a 6-month time frame, beginning on the liso-cel infusion date. HCRU data were analyzed in the 6 months after infusion, including facility (eg, number of standard IP and ICU hospitalizations and length of stay [LOS]), procedures (eg, dialysis or intubation/mechanical ventilation), diagnostics (eg, imaging or laboratory tests), and medication use (eg, tocilizumab or corticosteroids). Unit costs were then applied to each HCRU. Unit costs were assessed from the health care system perspective, derived from publicly available databases (eg, United States [US] Centers for Medicare &amp; Medicaid Services, Healthcare Cost and Utilization Project, and IBM ® Micromedex ® RED BOOK ®) or peer-reviewed literature, and adjusted to 2021 US dollars using the medical component of the Consumer Price Index. Patients were considered OP if discharged on the day of infusion or at the end of the observation period. Results: Among 150 patients treated with liso-cel, 111 (74%) were infused as IPs and 39 (26%) as OPs. Estimated median 6-month total postinfusion monitoring costs were $55,253 in the IP setting and $17,505 in the OP setting, reflecting a reduction of $37,748 for OP site of care (Figure). Among patients cared for in the OP setting who required subsequent hospitalization (19/39 [49%]), the median total LOS was 7 days shorter than patients cared for in the IP setting who required hospitalization (105/111 [95%]) (OP: 7 days [range, 1-33] vs IP: 14 days [range, 1-164]). Facility costs, especially hospitalizations, were the largest contributor to overall median 6-month costs in both the IP setting ($40,501; 73%) and the OP setting ($5697; 33%). The majority of total costs occurred in Month 1 postinfusion for patients in both settings. For patients receiving care in the IP setting, 78% ($42,864) of median costs were incurred within the first month after infusion; for OPs, 36% ($6295) of median costs were incurred within Month 1. Patients in the IP setting had higher rates of key HCRU than in the OP setting, respectively, for the following: standard IP hospitalizations (105/111 [95%] vs 19/39 [49%]), ICU admissions (10/111 [9%] vs 0/39 [0%]), any tocilizumab use (32/111 [29%] vs 5/39 [13%]), and any corticosteroid use (54/111 [49%] vs 17/39 [44%]). Patients in the OP setting had higher rates compared with the IP setting, respectively, for office visits (37/39 [95%] vs 87/111 [78%]) and intubation (2/39 [5%] vs 0/111 [0%]). Conclusions: Among patients with R/R LBCL treated with liso-cel in the 2L TRANSFORM and PILOT trials, estimated median 6-month postinfusion costs were 68% lower for patients cared for in the OP versus IP setting. These results are consistent with a previous analysis of patients treated with liso-cel in the third-line setting (Palomba ML, et al. Leuk Lymphoma 2021); and thus, further support that OP postinfusion monitoring and care may allow health care systems to optimize HCRU and costs for patients with LBCL who receive CAR T cell therapy.