First-line Treatment Regimens Research Articles

Using real world practice patterns to identify clinical equipoise in cancer treatment: Advanced non-small cell lung cancer as an exemplar.

539 Background: Novel therapies have improved the survival for patients with advanced non-small cell lung cancer (NSCLC). Clinical scenarios with high treatment variation indicate a lack of consensus about the standard of care, and can identify instances there is less clinical equipoise, and comparative effectiveness research is urgently needed. We quantified the variation in the first-line therapy, stratified by patient’s biomarker and Eastern Cooperative Oncology Group (ECOG) performance score. Methods: Using Flatiron database, we categorized patients with advanced NSCLC diagnosed between 1/1/2016 and 6/30/2020 into groups by biomarker findings and performance status. Patients with unknown status of biomarkers or negative actionable gene alterations, or missing ECOG score were excluded. The degree of variation in first-line treatment regimens was measured using the Herfindahl-Hirschman Index (HHI), which calculates the sum of squared proportion of patients receiving different regimen categories. The HHI ranges from close to 0 to 10,000, with low values indicate heterogeneous treatment patterns whereas high values indicate more uniformity in treatment patterns. We used bootstrapping to calculate 95% confidence intervals (CIs) for the HHI scores. Results: Our cohort consisted of 12,708 patients. Among them, 327 were ALK-positive, 1,816 were EGFR-positive, and 10,565 were ALK/EGFR negative or unknown (including 3,616 patients who were PD-L1 <1%, 3,139 PD-L1 1-49%, and 3,810 PD-L1 ≥50%, respectively). The HHI score for first-line therapy in our overall cohort was 2171 (95% CI: 2167, 2175). The HHI differed by biomarker status: 4403 for the EGFR+ group, 3809 for the ALK+ group, 3065 for the PD-L1 <1% group, 2925 for the PD-L1 1-49% group, and 3370 for the PD- L1 ≥50% group. When we stratified patients by both biomarker and ECOG status, the HHI ranged from 2791 (95% CI: 2740, 2840) for patients with PD-L1 1-49% and ECOG 2-4 to 5364 (95% CI: 5161, 5649) for patients with EGFR+ and ECOG 2-4 (details in Table). Conclusions: Using HHI, we were able to quantify and compare variation in treatment patterns across clinically distinct subgroups of patients. Large variation in the first-line therapy for patients with PD-L1 1-49% suggests lack of strong consensus regarding the optimal treatment regimens for these patients.[Table: see text]

Treatment Patterns and Outcomes Among Patients With Advanced or Recurrent Endometrial Cancer Initiating First-Line Therapy in the United States

Background: Patients with advanced or recurrent endometrial cancer (EC) typically have limited treatment options and poor long-term survival outcomes following first-line therapy. Real-world treatment patterns and survival outcomes data are limited for patients in this setting. Objectives: The objective of this retrospective study was to describe real-world demographics, clinical characteristics, treatment patterns, and overall survival among patients in the United States with primary advanced or recurrent EC who initiated at least 1 line of therapy (LOT). Methods: Patients with a diagnosis of primary advanced or recurrent EC in a real-world database from January 1, 2013, to July 31, 2021, were included. The date for inclusion was the date of EC diagnosis documentation; patients were indexed for treatment patterns and outcomes at the start of the first LOT and at the start of each subsequent LOT they initiated. Data were stratified by subgroups of patients who had mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) tumors. Results: A total of 1961 patients who received at least 1 LOT were included. Most patients in this cohort, and the dMMR/MSI-H subgroup, received a platinum combination as first-line treatment, with carboplatin-paclitaxel being the most common regimen. Only 53% of patients who received first-line treatment subsequently received second-line therapy. Of the patients who received at least 1 LOT, use of immunotherapy in the second-line setting was more common in the dMMR/MSI-H subgroup. Median overall survival ranged from 14.1 to 31.8 months across the 5 most frequently used first-line treatment regimens in the ≥1 LOT cohort and became shorter with each subsequent LOT. Discussion: The use of platinum-based chemotherapy for first-line treatment of advanced or recurrent EC predominates in the real-world setting, despite the poor long-term survival outcomes associated with most of these regimens. Conclusions: Patients with recurrent/advanced EC have a poor prognosis, highlighting the need for therapies with more durable benefits.

Treatment Patterns and Outcomes Among Patients With Advanced or Recurrent Endometrial Cancer Initiating First-Line Therapy in the United States.

Background: Patients with advanced or recurrent endometrial cancer (EC) typically have limited treatment options and poor long-term survival outcomes following first-line therapy. Real-world treatment patterns and survival outcomes data are limited for patients in this setting. Objectives: The objective of this retrospective study was to describe real-world demographics, clinical characteristics, treatment patterns, and overall survival among patients in the United States with primary advanced or recurrent EC who initiated at least 1 line of therapy (LOT). Methods: Patients with a diagnosis of primary advanced or recurrent EC in a real-world database from January 1, 2013, to July 31, 2021, were included. The date for inclusion was the date of EC diagnosis documentation; patients were indexed for treatment patterns and outcomes at the start of the first LOT and at the start of each subsequent LOT they initiated. Data were stratified by subgroups of patients who had mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) tumors. Results: A total of 1961 patients who received at least 1 LOT were included. Most patients in this cohort, and the dMMR/MSI-H subgroup, received a platinum combination as first-line treatment, with carboplatin-paclitaxel being the most common regimen. Only 53% of patients who received first-line treatment subsequently received second-line therapy. Of the patients who received at least 1 LOT, use of immunotherapy in the second-line setting was more common in the dMMR/MSI-H subgroup. Median overall survival ranged from 14.1 to 31.8 months across the 5 most frequently used first-line treatment regimens in the ≥1 LOT cohort and became shorter with each subsequent LOT. Discussion: The use of platinum-based chemotherapy for first-line treatment of advanced or recurrent EC predominates in the real-world setting, despite the poor long-term survival outcomes associated with most of these regimens. Conclusions: Patients with recurrent/advanced EC have a poor prognosis, highlighting the need for therapies with more durable benefits.

The influence of immunodeficiency, disease features, and patient characteristics on survival in plasmablastic lymphoma

AbstractPlasmablastic lymphoma (PBL) is a rare and aggressive non-Hodgkin lymphoma associated with immunodeficiency, characterized by uncertain treatment approaches and an unfavorable prognosis. We conducted a multicenter, international, retrospective cohort study, aiming to characterize the clinical features, risk factors, and outcomes of patients with PBL. Data were collected from 22 institutions across 4 countries regarding patients diagnosed with PBL between 1 January 1999 and 31 December 2020. Survival risk factors were analyzed using both univariate and multivariate regression models. Overall survival (OS) was calculated using Kaplan-Meier statistics. First-line treatment regimens were stratified into standard- and higher-intensity regimens, and based on whether they incorporated a proteasome inhibitor (PI). A total of 281 patients (median age, 55 years) were included. Immunodeficiency of any kind was identified in 144 patients (51%), and 99 patients (35%) had HIV-positive results. The 5-year OS for the entire cohort was 36% (95% confidence interval, 30%-42%). In multivariate analysis, inferior OS was associated with Epstein-Barr virus–negative lymphoma, poor performance status, advanced stage, and bone marrow involvement. In an independent univariate analysis, the international prognostic index was associated with OS outcomes. Neither immunosuppression nor HIV infection, specifically, influenced OS. Among patients treated with curative intent (n = 234), the overall response rate was 72%. Neither the intensity of the treatment regimen nor the inclusion of PIs in first-line therapy was associated with OS. In this large retrospective study of patients with PBL, we identified novel risk factors for survival. PBL remains a challenging disease with poor long-term outcomes.

834P Phase II clinical study of VR-CAP regimen for first-line treatment of marginal zone lymphoma

834P Phase II clinical study of VR-CAP regimen for first-line treatment of marginal zone lymphoma

Investigation on cognition, diagnosis and treatment status of chest tightness variant asthma among Chinese pediatricians

Objective: To evaluate the awareness, diagnosis and treatment of chest tightness variant asthma (CTVA) among pediatricians in China. Methods: The survey was conducted by convenient sampling method. Pediatricians with professional title of attending physician and above from different grades hospitals in 30 provinces were invited to conduct online questionnaire surveys through WeChat, pediatricians scan QR codes to complete electronic questionnaires in the mini program from January 16th to February 4th, 2021. The contents of questionnaire included the awareness, diagnosis and treatment of CTVA, and comparing the differences between pediatricians in secondary hospitals and tertiary hospitals. Results: A total of 1 529 pediatricians participated in the survey, and 1 484 (97.06%) pediatricians completed the questionnaire and included in the analysis, including 420 males (28.30%). The awareness rate of CTVA among pediatricians was 77.83 % (1 155/1 484). Pediatricians in tertiary hospitals had higher rates of awareness of CTVA than pediatricians in secondary hospitals [81.86% (898/1 097) vs 66.41% (257/387), P<0.001] and had better execution of the guidelines [89.15% (978/1 097) vs 79.59% (308/387), P<0.001]. A total of 93.06 % (1 381/1 484) of pediatricians' first-line treatment included inhaled corticosteroids (ICS) for CTVA. Among them, a higher proportion of pediatricians in tertiary hospitals used ICS included regimens for first-line treatment of CTVA compared with pediatricians in secondary hospitals [94.90% (1 041/1 097) vs 87.86% (340/387), P<0.001]. The reported well control rate of CTVA was 32.08% (476/1 484), which was significantly lower in secondary hospitals than that in tertiary hospitals [17.31% (67/387) vs 37.28% (409/1 097), P<0.001]. Conclusion: Most pediatricians are well aware of CTVA, among which there is a certain gap in clinical practice between pediatricians in secondary hospitals and tertiary hospitals in terms of understanding, diagnosis, and treatment of CTVA.

Ramucirumab plus FOLFIRI as second-line treatment for patients with RAS wild-type metastatic colorectal cancer previously treated with anti-EGFR antibody: JACCRO CC-16

Chemotherapy in combination with anti-epidermal growth factor receptor (EGFR) antibody is considered a first-line treatment regimen for RAS wild-type and left-sided metastatic colorectal cancer (mCRC), whereas second-line treatment regimens have not yet been established. Few studies have prospectively evaluated second-line treatment with anti-vascular endothelial growth factor antibody after first-line anti-EGFR antibody therapy for RAS wild-type mCRC. This non-randomized phase II trial investigated the clinical outcomes of second-line ramucirumab (RAM) plus fluorouracil, levofolinate, and irinotecan (FOLFIRI) after first-line anti-EGFR antibody in combination with doublet or triplet regimen in patients with RAS wild-type mCRC. The primary endpoint was the 6-month progression-free survival (PFS) rate. The secondary endpoints were PFS, overall survival (OS), objective response rate (ORR), rate of early tumor shrinkage (ETS), and safety. We hypothesized a threshold 6-month PFS rate of 30% and an expected 6-month PFS rate of 45%. Treatment was considered effective if the lower limit of the 90% confidence interval (CI) of the 6-month PFS rate was >0.30. Ninety-two patients were enrolled in the study. The primary tumor was located on the left side in 86 (95.6%) patients. Twenty (22.0%) patients had received triplet plus cetuximab as previous therapy. Six-month PFS rate was 58.2% (90% CI 49.3% to 66.2%) with a median PFS of 7.0 months (95% CI 5.7-7.6 months). Median OS was 23.6 months (95% CI 16.5-26.3 months). The ORR and ETS rate were 10.7% and 16.9%, respectively, in 83 patients with measurable lesions. The 6-month PFS rate was comparable between patients previously treated with doublet and triplet regimens; however, median PFS was longer for the doublet regimen (7.4 versus 6.4 months, P= 0.036). Our study demonstrated prospectively that RAM plus FOLFIRI is an effective second-line treatment after anti-EGFR antibody-containing first-line therapy in RAS wild-type and left-sided mCRC. Furthermore, the results were similar for patients who were previously treated with triplet regimen.

NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial

Pancreatic ductal adenocarcinoma remains one of the most lethal malignancies, with few treatment options. NAPOLI 3 aimed to compare the efficacy and safety of NALIRIFOX versus nab-paclitaxel and gemcitabine as first-line therapy for metastatic pancreatic ductal adenocarcinoma (mPDAC). NAPOLI 3 was a randomised, open-label, phase 3 study conducted at 187 community and academic sites in 18 countries worldwide across Europe, North America, South America, Asia, and Australia. Patients with mPDAC and Eastern Cooperative Oncology Group performance status score 0 or 1 were randomly assigned (1:1) to receive NALIRIFOX (liposomal irinotecan 50 mg/m2, oxaliplatin 60 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2, administered sequentially as a continuous intravenous infusion over 46 h) on days 1 and 15 of a 28-day cycle or nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2, administered intravenously, on days 1, 8, and 15 of a 28-day cycle. Balanced block randomisation was stratified by geographical region, performance status, and liver metastases, managed through an interactive web response system. The primary endpoint was overall survival in the intention-to-treat population, evaluated when at least 543 events were observed across the two treatment groups. Safety was evaluated in all patients who received at least one dose of study treatment. This completed trial is registered with ClinicalTrials.gov, NCT04083235. Between Feb 19, 2020 and Aug 17, 2021, 770 patients were randomly assigned (NALIRIFOX, 383; nab-paclitaxel-gemcitabine, 387; median follow-up 16·1 months [IQR 13·4-19·1]). Median overall survival was 11·1 months (95% CI 10·0-12·1) with NALIRIFOX versus 9·2 months (8·3-10·6) with nab-paclitaxel-gemcitabine (hazard ratio 0·83; 95% CI 0·70-0·99; p=0·036). Grade 3 or higher treatment-emergent adverse events occurred in 322 (87%) of 370 patients receiving NALIRIFOX and 326 (86%) of 379 patients receiving nab-paclitaxel-gemcitabine; treatment-related deaths occurred in six (2%) patients in the NALIRIFOX group and eight (2%) patients in the nab-paclitaxel-gemcitabine group. Our findings support use of the NALIRIFOX regimen as a possible reference regimen for first-line treatment of mPDAC. Ipsen. For the plain language summary see Supplementary Materials section.

Efficacy and safety of front-line treatment regimens for Waldenstrom macroglobulinaemia: a systematic review and meta-analysis

Rituximab-based chemo-immunotherapy is currently the standard first-line treatment for Waldenstrom macroglobulinaemia (WM), while ibrutinib has emerged as an alternative. In the absence of randomised trials (RCTs) comparing these regimens, the optimal first-line treatment for WM remains uncertain. In this systematic review and meta-analysis, we sought to assess the efficacy and safety of first-line treatment regimens for WM. We searched key databases from January 2007 to March 2023, including phase II and III trials, including treatment-naïve WM patients treated with rituximab-based regimens or ibrutinib. Response rates, progression-free survival (PFS), overall survival (OS), and toxicities were evaluated. Four phase III and seven phase II trials were included among 736 unique records. Pooled response rates from all comparative and non-comparative trials were 46%, 33% and 26% for bendamustine rituximab (BR), bortezomib-dexamethasone, cyclophosphamide, rituximab (BDRC) and ibrutinib rituximab (IR), respectively. Two-year pooled PFS was 89%, 81% and 82% with BR, BDRC and IR, respectively. Neuropathy was more frequent with bortezomib, while haematologic and cardiac toxicities were more common with chemo-immunotherapy and ibrutinib-based regimens respectively. Our findings suggest that BR yields higher response rates than bortezomib or ibrutinib-based combinations. RCTs comparing BR against emerging therapies, including novel Bruton Tyrosine Kinase Inhibitors, are warranted.

EFFICACY AND SAFETY OF GEMIFLOXACIN CONTAINING TREATMENT REGIMEN IN FIRST-LINE TREATMENT OF HELICOBACTER PYLORI.

•In eradication treatment of H. pylori gemifloxacin containing triple treatment regimen was as effective as bismuth containing quadruple treatment. •Drug adverse effects were fewer and milder in the gemifloxacin group. •Since treatment period was shorter and pills to be taken were fewer compared to quadruple treatment, patient compliance was significantly higher in the gemifloxacin group. Background - After eradication of Helicobacter pylori (H. pylori) chronic gastritis will resolve, complications due to H. pylori infection and recurrence of infection will be prevented. Objective - To determine efficacy and safety of gemifloxacin containing treatment regimen in first line treatment of H. pylori with comparison to bismuth containing quadruple therapy. Methods - This retrospective study was conducted in a tertiary care university hospital between January 2018 and January 2021 with 410 participants who were diagnosed to have H. pylori infection with biopsies obtained during upper gastrointestinal system endoscopy. Patients were distributed into two groups according to their first-line treatment regimens. First group patients were treated with amoxicillin, gemifloxacin and pantoprazole and second group patients were treated with amoxicillin, metronidazole, bismuth subcitrate and pantoprazole for seven days. Results - Intention to treat and per protocol ratios for gemifloxacin containing regimen were 90.0% and 91.2%, while quadruple treatment has these ratios as 91.7% and 93.8% respectively. Treatment success rate in both regimens were similar. But adverse effects were lower and patient compliance were better in patients who had gemifloxacin containing treatment (P<0.001). Conclusion - Gemifloxacin containing treatment regimen is as effective as bismuth containing quadruple treatment regimen for H. pylori infection and patient compliance is better in this group. Gemifloxacin containing treatment regimens may be novel and effective alternatives for eradication of H. pylori infection.

Ilaprazole-amoxicillin dual therapy at high dose as a first-line treatment for helicobacter pylori infection in Hainan: a single-center, open-label, noninferiority, randomized controlled trial

ObjectivesThis study aimed to evaluate the efficacy, adverse events, patient compliance, and cost of dual therapy with Ilaprazole-amoxicillin (IA) at high dose versus Ilaprazole-amoxicillin-furazolidone-bismuth (IAFB) quadruple therapy for the Helicobacter pylori (H.pylori) infection among Chinese patients.Methods200 patients who had tested positive for H. pylori and undergoing upper gastrointestinal endoscopy after being diagnosed with chronic gastritis participated in this open-label randomized controlled clinical trial. Patients were randomized to Group A and Group B: the 14-day IA dual treatment group (101) and IAFB quadruple treatment group (99). The 13 C urea breath test was conducted to determine whether H. pylori had been eliminated 4–6 weeks after the treatment. Eradication rates, drug-related adverse events, patient compliance, and drug costs were compared between the two treatment groups.ResultsEradication rates in group A were 92.1% and 94.9%, depending on the intention-to-treat (ITT), per-protocol (PP), respectively, which was similar to group B (91.9% and 93.6%). There was no significant difference observed in adverse events between the two groups (P = 0.518). Interestingly, compliance was significantly higher in group A compared to the group B (P = 0.031). In addition, drug costs were significantly lower for group A in comparison to the group B.ConclusionsIA dual therapy was found to be equally effective, safer and less costly than IAFB quadruple therapy. Therefore, these therapies can be potentially considered as first-line regimens for empirical treatment.

Low-Molecular-Weight Heparin Versus Warfarin in Adult Cancer Patients as a Precision Medicine for Thrombosis: A Systematic Review and Meta-Analysis.

Venous thromboembolism (VTE) is a conditionoften seen in patients diagnosed with cancer and is recognized as a predictor of poor outcomes in these patients. The probability ofVTE recurringis generally higher in people with cancer than in those without; hence, addressing this issue is essential when making healthcare decisions. Therefore, our systematic review was primarily designed to compare low-weight- molecular heparin (LMWH) to warfarin in reducing recurrent VTE among cancer patients. However, other outcomes were also evaluated, such as mortality and bleeding events observed more in cancer patients. The selection of relevant articles was carried out using a database search and a manual search, which involved reviewing reference lists of articles eligible for inclusion in the current review. The methodological quality of each included study was then assessed using Cochrane's risk of bias tool in the Review Manager software (RevMan 5.4.1). Additionally, pooled results were examined using the Review Manager software and presented as forest plots. Our search of electronic databases elicited a total of 2163 articles, of which only six were deemed eligible for inclusion and analysis. Data pooled from the six studies demonstrated the effectiveness of LMWH in minimizing the reoccurrence of VTE over warfarin [risk ratio (RR): 0.67; 95% CI: 0.47 - 0.95; p = 0.03]. However, LMWH had a similar effect statisticallyas warfarin on the major bleeding events (RR: 1.05; 95% CI: 0.62 - 1.77; p = 0.85), minor bleeding events (RR: 0.80; 95% CI: 0.54 - 1.20; p = 0.28), and all-cause mortality (RR: 1.00; 95% CI: 0.88 - 1.13; p = 0.99). While LMWH demonstrated its effectiveness in minimizing the incidence of VTE recurrence over warfarin in cancer patients, it had no statistical difference in terms of mortality or bleeding events when compared to warfarin. Based on our findings, we recommend that LMWH continues to be usedas a first-line treatment regimen to mitigate recurrent VTE in cancer patients.

Comparison of International Prognostic Indices and Validation Study for Patients with Diffuse Large B-Cell Lymphoma in the Rituximab Era

ABSTRACT In diffuse large B-cell lymphoma (DLBCL), patients needing new alternative regimens in first-line treatment should be selected with better risk classification. After International Prognostic Index (IPI), Revised-IPI (R-IPI), National Comprehensive Cancer Network (NCCN)-IPI, and Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO)-IPI, have been developed to improve risk predictions. This study compared performances of four prognostic indices concerning differentiation of overall survival (OS), the most critical endpoint. The study was conducted on 116 patients diagnosed with DLBCL. Patients with primary nervous system and testicular DLBCL, and post-transplant lymphoproliferative disorders, were excluded. The fitting of prognostic indices for database and the prediction of patient discrimination were compared using Akaike’s information criterion and concordance index. Of the study cohort, 63.8% were male, the median age was 56 (18-88), and median follow-up term was 45.6 (0.3-75.2) months. All factors, constituting IPI and R-IPI scores, demonstrated a significant difference in OS. Involvements of the extranodal regions specified in NCCN-IPI and elevated serum beta-2 microglobulin levels in GELTAMO-IPI had prognostic significance (p= 0.005 and p= 0.040, respectively). Each of the four prognostic indices, resulted in risk groups with significantly different OS. R-IPI provided the best fit for database, while NCCN-IPI provided the best discrimination between patients with high and low OS. Although NCCN-IPI provides the best discrimination between patients with short and long OS, using original IPI still seems acceptable in the rituximab era. Integration of tumor molecular characteristics into NCCN-IPI may better characterize high-risk group in new treatment approaches. Keywords: International Prognostic Index, National Comprehensive Cancer Network, Validation, Diffuse Large B-Cell Lymphoma, Rituximab

Treatment-Free Survival After Nivolumab vs Pembrolizumab vs Nivolumab-Ipilimumab for Advanced Melanoma

Treatment-free survival (TFS) represents an alternative time-to-event end point, accurately characterizing time spent free of systemic therapy, providing a more patient-centric view of immune checkpoint inhibitor (ICI) therapy regimens. There remains a lack of studies evaluating TFS outcomes among patients with advanced melanoma who are receiving immunotherapy, especially outside of the clinical trial setting. To evaluate TFS outcomes for patients with advanced melanoma receiving first-line ICI therapy outside of a clinical trial setting. This multicenter cohort study of patients with advanced melanoma receiving first-line ICI therapy between August 1, 2013, and May 31, 2020, was conducted in Alberta, Canada. Data analysis was performed in August 2022. Patients received standard-of-care, first-line ICI therapy treatment regimens including single-agent nivolumab, single-agent pembrolizumab, or ipilimumab-nivolumab. Treatment-free survival was defined as the difference in the 36-month restricted mean survival time between 2 conventional survival end points: (1) time from treatment initiation to ICI cessation, death, or censoring at last follow-up and (2) time from treatment initiation to subsequent systemic anticancer therapy, death, or censoring at last follow-up. A total of 316 patients with advanced melanoma receiving first-line nivolumab (n = 51; median age, 66 years [IQR, 56-78 years]; 31 men [60.8%]), pembrolizumab (n = 158; median age, 69 years [IQR, 60-78 years]; 112 men [70.9%]), or combination nivolumab-ipilimumab (n = 107; median age, 53 years [IQR, 42-60 years]; 72 men [67.3%]) were included. Treatment groups were similar with regard to sex, primary tumor location, and presence of metastasis, although patients receiving combination nivolumab-ipilimumab had a lower Eastern Cooperative Oncology Group status, were younger, and were more likely to be BRAF V600E positive than those receiving anti-programmed cell death protein 1 (anti-PD-1) monotherapy. The restricted mean TFS was longer for nivolumab-ipilimumab (12.4 months [95% CI, 8.8-16.0 months]) compared with nivolumab (8.9 months [95% CI, 4.4-13.5 months]) and pembrolizumab (11.1 months [95% CI, 8.5-13.8 months]). During the 36-month follow-up interval, patients treated with nivolumab-ipilimumab spent 34.4% of their time (12.4 of 36 months) not receiving systemic anticancer treatments compared with 30.8% (11.1 of 36 months) and 24.7% (8.9 of 36 months) of the time for the pembrolizumab and nivolumab treatment groups, respectively. This cohort study of patients with advanced melanoma receiving first-line ICI therapy suggests that TFS represents a patient-centric, informative end point. Patients treated with combination nivolumab-ipilimumab spent more time alive and free from systemic anticancer therapy than those treated with anti-PD-1 monotherapy alone.

BTK INHIBITORS IN CNSL AND HIGH‐RISK/REFRACTORY DLBCL PATIENTS: A REAL‐WORLD STUDY

Objective: The effectiveness and prognosis of a BTki-containing regimen in first-line treatment and relapsed/refractory patients were assessed in this study. Methods: There were 26 patients with DLBCL. BTKi was administered to patients with newly diagnosed, relapsed, refractory primary PCNSL and high-risk/refractory systemic DLBCL, and the effectiveness and PFS were evaluated. Results: The BTKi therapy study included 26 participants (16 PCNSL, 10 DLBCL). Among PCNSL,3 patients who had achieved PR following MTX-based first-line chemotherapy were given BTKi as a monotherapy for disease recurrence. BTKi patients lived for an average of 5 (1–8) months before dying from disease progression, which is 5 months longer than the typical patient survival period following chemotherapy recurrence. After three rounds of MTX-based chemotherapy, none of the six patients with refractory PCNSL achieved PR. After BTKi was utilized as second-line therapy, the average survival time was increased by 12 (2–21) months. Three patients received early treatment, while the remaining three received BTKi after the third round of medicine. Early patients had a longer average survival period than late ones (11 months vs. 10 months). The remaining seven high-risk patients received first-line chemotherapy and BTKi treatment. The median follow-up duration was 5 months, the ORR was 100%, and neither the median PFS nor the median OS were achieved. The mean maintenance time was 8 months. Among 10 patients with DLBCL, 8 of them are high risk group, and 2 had refractory disease. When the disease of two SCNSL patients advanced, BTKi was used in conjunction with chemotherapy as a salvage treatment, and BTKi was kept up for an average of 5 months. The efficacy was evaluated as PD. The ORR was 80% (4/5, 1 case was not assessed) and CR rate was 100% in high risk group. Four of these CNS-IPI high-risk DLBCL patients had adrenal involvement and a high IPI score, with BTKi maintained for an average of 6 months, two of them achieved CR, one of PD, and 1 case was not evaluated. The efficacy evaluation was CR in the other two high-risk CD5+ patients, whose BTKi was sustained for 12 months and 6 months, respectively. After receiving standard chemotherapy, the remaining 2 refractory patients kept getting worse. One patient with hepatitis B cirrhosis had elevated AST and ALT levels after one course of medication, so BTKi was stopped. The other patient was kept on BTKi alone for 4 months, but the efficacy was still PD. Patients with PCNSL have a dismal prognosis, in particular, the average survival time for R/R patients is less than two months. The research was funded by: National Natural Science Foundation of China (8226010026), Natural Science Foundation of Gansu Province (22JR11RA053) Keywords: aggressive B-cell non-Hodgkin lymphoma, molecular targeted therapies, combination therapies No conflicts of interests pertinent to the abstract.

Patient-reported outcome (PRO)-based symptom assessment in patients with advanced lung cancer receiving first-line combination immunotherapy: a protocol for a multicenter, prospective, observational study

BackgroundImmunotherapy is currently applied in the first-line treatment regimens for numerous advanced cancers, especially advanced lung cancer. Immune-related adverse events (irAEs) resulting from immunotherapy can vary in severity and cause a substantial symptom burden to patients. However, there are limited data on symptom burden in patients with advanced lung cancer following immunotherapy. To address this deficit, this study aims to provide insight into the symptom burden and severity through patient-reported outcome measurements and conduct an analysis of temporal trends and clinical consequences of symptom burden in patients with advanced lung cancer receiving combination immunotherapy.MethodsWe will prospectively recruit 168 eligible patients from 14 hospitals in China. Eligible patients will be aged ≥ 18 years, pathologically diagnosed with locally advanced or stage IV primary lung cancer without surgical indications, and agreed to receive immunotherapy in combination with other therapies. The primary outcome of this study is the symptom burden of patients during the immunotherapy course. Longitudinal symptom data will be collected using the MD Anderson Symptom Inventory–Lung Cancer module (MDASI-LC) and the symptomatic irAEs scale at baseline (once before treatment) and weekly after treatment, until 1 month after the last treatment cycle has been completed. The trajectory of symptom burden following combination immunotherapy will be depicted, and by linking it to clinical outcomes (the secondary outcome and exploratory outcome of this study), the consequence of symptom burden in patients with advanced lung cancer receiving combination immunotherapy will be examined further.DiscussionThis study intends to establish longitudinal symptom trajectories in patients with lung cancer receiving immunotherapy, and explore its association with clinical outcomes. These findings may serve as an important reference for clinicians in the symptomatic management of patients with lung cancer receiving immunotherapy.Trial registration numberChiCTR2200061540. Registered on June 28, 2022.

Intracranial activity of first-line immune checkpoint inhibitors combined with chemotherapy in advanced non-small cell lung cancer.

Immune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis. Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy ( n = 102) or chemotherapy ( n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups. Compared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% [45/102] vs . 28.4% [31/109], χ2 = 5.620, P = 0.013) and systemic (49.0% [50/102] vs . 33.9% [37/109], χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs . 7.0 months, P <0.001) and systemic (9.0 months vs . 5.0 months, P <0.001) PFS. Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.37-0.73, P <0.001) and systemic PFS (HR = 0.48, 95% CI: 0.35-0.66, P <0.001). No unexpected serious adverse effects were observed. Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis. https://www.clinicaltrials.gov/ , OMESIA, NCT05129202.

Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non-Small-Cell Lung Cancer.

Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m2 on day 1 and gemcitabine 1,250 mg/m2 on days 1 and 8 (n = 863) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day 1 (n = 862) every 3 weeks for up to six cycles. Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia (P ≤ .001); febrile neutropenia (P = .002); and alopecia (P < .001) were significantly lower, whereas grade 3 or 4 nausea (P = .004) was more common. In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.

Effectiveness and safety of capecitabine, irinotecan and panitumumab in advanced colorectal cancer.

Capecitabine, irinotecan, and panitumumab (CAPIRI-P) is a controversial regimen for metastatic colorectal cancer, with concerns regarding the efficacy and toxicity. However, its toxicity profile has been improved with dose reduction, and concerns regarding efficacy have been extrapolated from other trials. This retrospective study reports the real-world effectiveness and safety of modified CAPIRI-P (mCAPIRI-P). Advanced colorectal cancer patients receiving mCAPIPI-P in the first-line setting between July 2019 and December 2021 were analyzed. The progression-free survival on treatment (PFSOT) and overall survival (OS) were estimated using the Kaplan-Meier method, and the association with clinical and disease factors was analyzed using the Cox regression model. Serial changes in carcinoembryonic antigen (CEA) level and treatment toxicity were also evaluated. A total of 106 patients were included, of whom 97 (92%) and 31 (29%) had left-sided primary and unresectable liver-only disease, respectively. The median PFSOT and OS were 15.4 (95% CI 12.5-18.3) and 25.5 (95% CI 17.6-33.4) months, respectively. Sixteen (51.6%) and 10 (32.3%) liver-only disease patients underwent secondary liver treatment and R0 resection, respectively. In multivariable Cox regression, CEA responders (PFSOT: HR 0.53) and CEA normalization (PFSOT: HR 0.27; OS: HR 0.28) were independent favorable prognostic factors for PFSOT and OS. Grade ≥3 toxicity rate was 43%, mainly related to uncomplicated hematological toxicities. The real-world data show that mCAPIRI-P is safe and effective as the first-line treatment regimen for RAS wild-type advanced colorectal cancer and warrants further study.

Abstract 6485: Oxidative phosphorylation-associated radiomic feature and survival of women with serous ovarian cancer

Abstract Novel biomarkers that can be utilized for clinical decision support to improve patient outcomes are critically needed for ovarian cancer. At present, there are no standard of care biomarkers to inform the first-line treatment regimen (neoadjuvant chemotherapy vs. upfront surgical debulking) best suited for each patient or which patients are at the highest risk of recurrence. To address this unmet need, we identified pre-treatment computed tomography (CT) image-based radiomic features predictive of outcomes and primary treatment response among 298 women diagnosed with serous ovarian cancer from 2008 to 2019. A decision tree analysis identified a single volumetric feature, region of interest (ROI) volume center of mass (CoM) in the X direction, as the most informative radiomic feature that stratified patients with upfront surgery into high- and low-risk groups for overall survival. The high-risk group consists of patients with higher values of the radiomic feature. In the training (N=91) and test (N=91) cohorts of women treated with upfront surgery, high-risk patients had worse survival compared to low-risk patients (HR=2.01, 95% CI=1.07, 3.77 and HR=2.23, 95% CI=1.19, 4.17, respectively). This radiomic feature was not associated with survival among women treated with neoadjuvant chemotherapy (N=116; HR=1.23, 95% CI=0.73, 2.07). To reveal potential underlying biology of this radiomic feature, we performed RNAseq gene expression profiling on 47 formalin-fixed paraffin-embedded tumor specimens and correlated gene expression with the radiomic feature using DESeq2 from RSEM estimates. Dichotomized analysis (high- vs. low-risk) yielded 7 significant genes and continuous analysis yielded 15 significant genes (adjusted p&amp;lt;0.05), with both approaches identifying AKT2 and PSMC4. Gene set enrichment analysis (GSEA) was used to identify enriched gene sets from continuous associations using the MSigDB Hallmarks pathways (adjusted p&amp;lt;0.05). GSEA identified the oxidative phosphorylation (OXPHOS) pathway as one of the gene sets most negatively associated with the predictive radiomic feature (Hallmark Normalized Enrichment Score=-2.28, adjusted p&amp;lt;0.001). We derived a PCA-based gene signature from significantly associated OXPHOS genes (p&amp;lt;0.01) resulting in a negative correlation with the radiomic feature (R=-0.65, p&amp;lt;0.001). Prior studies have shown that high OXPHOS ovarian tumors are associated with an increased response to conventional chemotherapy, suggesting that OXPHOS may be a key pathway for chemoresistance in ovarian cancer. In summary, we identified an OXPHOS-associated radiomic feature predictive of survival among women with serous ovarian cancer treated with upfront surgery. Further research is needed to elucidate the biologic and mechanistic underpinnings of the identified radiomic feature and to validate these findings in a larger cohort of women with ovarian cancer. Citation Format: Christelle Colin-Leitzinger, Jaileene Perez-Morales, Steven Eschrich, Jamie K. Teer, Sweta Sinha, Melissa J. McGettigan, Daniel K. Jeong, Olya Stringfield, Mahmoud A. Abdalah, Natarajan Raghunand, Robert J. Gillies, Jing-Yi Chern, Matthew Schabath, Lauren Cole Peres. Oxidative phosphorylation-associated radiomic feature and survival of women with serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6485.