First-line Chemotherapy In Patients Research Articles

PD58-12 CROSS-REACTIVITY BETWEEN THE FIRST-LINE CHEMOTHERAPY AND SUBSEQUENT IMMUNOTHERAPY IN PATIENTS WITH UNRESECTABLE OR METASTATIC UROTHELIAL CARCINOMA

You have accessJournal of UrologyCME1 May 2022PD58-12 CROSS-REACTIVITY BETWEEN THE FIRST-LINE CHEMOTHERAPY AND SUBSEQUENT IMMUNOTHERAPY IN PATIENTS WITH UNRESECTABLE OR METASTATIC UROTHELIAL CARCINOMA Tomoko Hamaya, Shingo Hatakeyama, Kai Ozaki, Kazutaka Okita, Yasuhiro Hashimoto, and Chikara Ohyama Tomoko HamayaTomoko Hamaya More articles by this author , Shingo HatakeyamaShingo Hatakeyama More articles by this author , Kai OzakiKai Ozaki More articles by this author , Kazutaka OkitaKazutaka Okita More articles by this author , Yasuhiro HashimotoYasuhiro Hashimoto More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002643.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Immunotherapy is beneficial in patients with unresectable locally advanced or metastatic UC. The JAVELIN Bladder 100 trial demonstrated that the survival benefit of avelumab maintenance therapy in selected patients with favorable response to the first-line chemotherapy. This observation may suggest that a favorable response to first-line chemotherapy might be associated with a favorable response to subsequent immunotherapy. However, not enough data is available for the cross-reactivity between the first-line chemotherapy and subsequent immunotherapy. Therefore, we retrospectively investigated the cross-reactivity between the first-line chemotherapy and subsequent immunotherapy in patients with advanced UC. METHODS: We evaluated 218 patients with advanced UC (T4, N positive, or M1) who received systemic, platinum-based, first-line chemotherapy from May 2003 to August 2021. The primary objective was comparison of overall survival between the patients treated with or without second-line immune checkpoint inhibitor (ICI) who had no progressive disease (PD) ≤4 cycles of the first-line chemotherapy (the non-PD ≤4 group). Secondary objective was to evaluate overall survival between the patients treated with or without second-line ICI who had PD ≤4 cycles of the first-line chemotherapy (the PD ≤4 group). RESULTS: The median age was 71 years. The numbers of patients with the non-PD ≤4 and PD ≤4 groups were 84 and 134, respectively. In the non-PD ≤4 group, we observed significantly longer overall survival in patients treated with ICI than those without. The difference in the median survival reached 37 months (26 vs. 63 months, P = 0.039). Conversely, there was no significant difference in overall survival in the PD ≤4 group. The multivariable Cox regression analysis showed that administration of ICI, performance status, and non-PD ≤4 were significantly associated with overall survival. CONCLUSIONS: The favorable tumor response to the first-line chemotherapy was significantly associated with longer survival in advanced UC patients with subsequent immunotherapy than those without. There may be cross-reactivity between chemotherapy and subsequent immunotherapy. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1017 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tomoko Hamaya More articles by this author Shingo Hatakeyama More articles by this author Kai Ozaki More articles by this author Kazutaka Okita More articles by this author Yasuhiro Hashimoto More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement PDF DownloadLoading ...

188P Pooled analysis of two phase II randomised studies (NorBreast-231 & TEMPO Breast) evaluating weekly oral vinorelbine (VNR) as first-line chemotherapy in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC)

Single-agent chemotherapy is a valuable option for patients with ABC, and weekly oral VNR is a recommended treatment. NorBreast-231 evaluated activity and tolerability of paclitaxel and oral VNR, while TEMPO Breast explored weekly versus metronomic VNR. The results of TEMPO Breast showed numerically higher disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) for standard weekly VNR in this setting, possibly due to a ‘peak effect’ with weekly dosing. We performed a pooled analysis of the weekly arm of these two trials.

Antibiotic Treatment Improves the Efficacy of Oxaliplatin-Based Therapy as First-Line Chemotherapy for Patients with Advanced Gastric Cancer: A Retrospective Study.

PurposeOne of the first-line treatment for gastric cancer patients is oxaliplatin, and the efficacy of this chemotherapeutic can be attenuated by the microbiome. In this study, we retrospectively evaluated whether treatment with antibiotics improved the efficacy of oxaliplatin-based chemotherapy in patients with advanced gastric cancer.Patients and MethodsFifty-four patients were assigned to the antibiotic-treated group and 35 to the antibiotic-untreated group.ResultsThe response rate of oxaliplatin-based chemotherapy in the antibiotic-treated and antibiotic-untreated groups was 66.7% and 41.4%, respectively (p = 0.038). The median progression-free survival after oxaliplatin-based chemotherapy in the antibiotic-treated and antibiotic-untreated groups was 8.8 and 5.2 months, respectively (hazard ratio = 0.456, 95% confidence interval = 0.254–0.819; p = 0.007, Log rank test). Univariate and multivariate analyses revealed that antibiotic treatment was the only clinical parameter that correlated with the response to oxaliplatin.ConclusionAntibiotic treatment could be used therapeutically to enhance the efficacy of oxaliplatin-based chemotherapy in patients with advanced gastric cancer.

Treatment Trends and Clinical Outcomes of Left-Sided RAS/RAF Wild-Type Metastatic Colorectal Cancer in the United States.

Post hoc analysis of the CALGB/SWOG 80405 trial suggests that anti-EGFR therapy may be superior to bevacizumab when added to first-line chemotherapy in patients with metastatic colorectal cancer (mCRC) who have left-sided primary tumors. We evaluated trends in use of anti-EGFR agents in patients with left-sided RAS/RAF wild-type (WT) mCRC and compared clinical outcomes among the most commonly used treatment strategies. A nationwide electronic health record (EHR)-derived deidentified database was reviewed for patients with left-sided RAS/RAF WT mCRC. Treatment trends over time were assessed by fitting a linear model to the percentage of patients receiving anti-EGFR therapy. A propensity score weighted Cox model was used to compare overall survival (OS) stratified by first-line targeted therapy received. A total of 1,607 patients with left-sided RAS/RAF WT mCRC received standard first-line chemotherapy. Of these, 965 (60%) received bevacizumab and 186 (12%) received an anti-EGFR agent. The percentage of patients receiving an anti-EGFR increased from 9% in 2013 to 16% in 2018. Median OS for patients treated with chemotherapy alone was 27.3 months (95% CI, 24.8-32.3), 27.5 months with bevacizumab (95% CI, 25.8-28.9; hazard ratio [HR], 0.88; P=.33), and 42.9 months with an anti-EGFR agent (95% CI, 36.0 to not reached; HR, 0.52; P=.005). This analysis suggests that chemotherapy with bevacizumab remained the most widely used first-line treatment strategy for patients with left-sided RAS/RAF WT mCRC in the United States in 2018. Despite this preference, treatment with an anti-EGFR agent was associated with improved OS.

Immune Contexture and Differentiation Features Predict Outcome in Bladder Cancer

BackgroundAn improved risk assessment of patients with bladder cancer (BC) is important to optimize clinical management. ObjectiveTo identify whether immune cell subpopulations and cancer cell-intrinsic features are associated with outcome and response to first-line chemotherapy in BC. Design, setting, and participantsPrimary tumor tissue from 785 patients with BC (stage Ta-T4b) were stained using multiplex immunofluorescence (CD3, CD8, FOXP3, CD20, CD68, CD163, and MHC-I) and immunohistochemistry (pancytokeratin, CK5/6, GATA3, programmed death 1 [PD-1], and programmed death ligand 1 [PD-L1]). A digital image analysis quantified staining results within the carcinoma cell and stromal part of the tumor. Outcome measurements and statistical analysisPrimary endpoints were progression-free survival, recurrence-free survival, and response to first-line chemotherapy. Optimal cutoff values for investigated markers were estimated using maximally selected rank statistics and receiver operating characteristic for each primary endpoint. Time-to-event analyses were performed using Cox regression analyses. Results and limitationsSeveral immune subpopulations were independently associated with clinical outcomes. Especially, high PD-1 and PD-L1 expression was independently associated with an increased risk of recurrence and progression in non–muscle-invasive tumors, but with a lower risk of recurrence in muscle-invasive tumors. Furthermore, we observed a lower likelihood of response to first-line chemotherapy in patients with basal differentiation features. Finally, a model combining clinical risk factors with our most evident prognosticator improved prediction accuracy compared with clinical risk factors alone for progression in non–muscle-invasive BC and recurrence in muscle-invasive BC. The use of tissue microarrays and a long inclusion period are limitations to this study. ConclusionsImmune cell subpopulations and cancer cell-intrinsic features are associated with different clinical outcomes in BC. Patient summaryImmune cells play an important role in cancer development and treatment outcomes. Infiltration with specific immune cells and the presence of markers associated with immune evasion in the tumor predict clinical outcomes in bladder cancer.

A multicenter real-life U.K. study of use of immunotherapeutic agents in metastatic urothelial cancer.

504 Background: First-line chemotherapy for patients with cisplatin-ineligible metastatic urothelial carcinoma (mUC) is associated with short response duration and high toxicity. Pembrolizumab(PEM) and atezolizumab (ATZ) are associated with long-term, durable remissions as a first-line treatment of cisplatin-ineligible, PD-L1-positive patients with mUC. For patients who progressed during or after platinum-based chemotherapy, Immunotherapy also prolongs survival with less toxicity and better quality of life compared with further lines of chemotherapy. There have been no studies directly comparing the effectiveness of PEM to ATZ in mUC patients. Methods: A cohort of 112 patients from 3 UK centres were included. 62, previously untreated cisplatin ineligible mUC patients who showed PDL1 positivity were given either ATZ or PEM once every 3 weeks until progression. 49 patients who had initial platinum based chemotherapy subsequently had ATZ or PEM as second line treatment following their disease progression The primary endpoint was Overall Survival(OS) and secondary endpoints included objective rate(ORR), response duration and safety. Results: The median age was 69 ( Interquartile range 43-91) and 23% were female and 77% were male. Among, patients who received immunotherapy 1st line, 82% had baseline renal impairment(GFR < 60), and 18% had Eastern Cooperative Oncology Group performance status 2. For chemo naïve patients, median OS was 11.5 months for PEM and 5 months for ATZ respectively. ORR was 22 % for ATZ vs 50% for PEM and median duration of treatment was 4.5 and 2.5 months for PEM and ATZ respectively. When used in 2nd line median OS is 7 months for ATZ irrespective of PDL1 status and not reached for PEM yet. Grade 2 and above toxicities were reported in 18 % ATZ patients vs 10% in PEM patients, commonest were pneumonitis, tiredness, hepatitis and dermatitis. No treatment related deaths were reported. Conclusions: This study suggests that pembrolizumab has higher response rate and better survival compared to atezolizumab in cisplatin-ineligible patients with mUC and also in the 2nd line setting after disease progression following platinum based agents. Both agents were well tolerated.

Lapatinib as first-line treatment for muscle-invasive urothelial carcinoma in dogs

Epidermal growth factor receptors 1 and 2 (EGFR and HER2) are frequently overexpressed in various malignancies. Lapatinib is a dual tyrosine kinase inhibitor that inhibits both EGFR and HER2. Although a phase III trial failed to show the survival benefits of lapatinib treatment after first-line chemotherapy in patients with EGFR/HER2-positive metastatic urothelial carcinoma, the efficacy of lapatinib for untreated urothelial carcinoma is not well defined. Here, we describe the therapeutic efficacy of lapatinib as a first-line treatment in a canine model of muscle-invasive urothelial carcinoma. In this non-randomized clinical trial, we compared 44 dogs with naturally occurring urothelial carcinoma who received lapatinib and piroxicam, with 42 age-, sex-, and tumor stage-matched dogs that received piroxicam alone. Compared to the dogs treated with piroxicam alone, those administered the lapatinib/piroxicam treatment had a greater reduction in the size of the primary tumor and improved survival. Exploratory analyses showed that HER2 overexpression was associated with response and survival in dogs treated with lapatinib. Our study suggests that lapatinib showed encouraging durable response rates, survival, and tolerability, supporting its therapeutic use for untreated advanced urothelial carcinoma in dogs. The use of lapatinib as a first-line treatment may be investigated further in human patients with urothelial carcinoma.

A Nomogram Combining Neutrophil-to-Lymphocyte Ratio and D-Dimer Predicts Chemosensitivity of Oxaliplatin-Based First-Line Chemotherapy in Patients with Unresectable Advanced Gastric Cancer.

Introduction: No effective peripheral blood predictors have been establoshed for first-line chemotherapy in patients with advanced gastric cancer. In this study, a nomogram combining the neutrophil-to-lymphocyte ratio/D-dimer with gender, number of metastases, and histological grade was established to predict progression-free survival in patients with unresectable advanced gastric cancer. Methods: We retrospectively collected baseline clinical characteristics and blood parameters from 153 patients diagnosed with advanced gastric cancer that underwent oxaliplatin-based first-line chemotherapy. Kaplan–Meier analysis and Cox regression analysis were used to determine the factors associated with progression-free survival. The concordance index (C-index) and calibration curve were used to determine the prediction accuracy and discriminative ability of the nomogram as a visual complement to the prognostic score system. Results: Determined by the X-tile software, the optimal cut-off points for the neutrophil-to-lymphocyte ratio and D-dimer were 3.18 and 0.56 mg/L, respectively. Multivariate analysis identified four independent prognostic factors: two or more metastatic organs (HR: 1.562, 95% CI: 1.009-2.418, P = .046), poor differentiation (HR: 0.308, 95% CI: 0.194-0.487, P < .001), neutrophil-to-lymphocyte ratio >3.18 (HR: 1.427, 95% CI: 1.024-1.989, P = .036), and D-dimer >0.56 mg/L (HR: 1.811, 95% CI: 1.183-2.773, P = .006). Receiver operating characteristic curves showed that the combination of the neutrophil-to-lymphocyte ratio and D-dimer in the prediction model exhibited the highest predictive performance (area under the curve, 0.800). The prognostic nomogram yielded a C-index of 0.800. Decision curve analysis demonstrated that the prognostic nomogram was clinically useful. A nomogram-based risk classification system was also constructed to facilitate risk stratification of advanced gastric cancer for optimal clinical management. Conclusion: We identified the neutrophil-to-lymphocyte ratio and D-dimer level as independent prognostic factors for advanced gastric cancer. The prognostic nomogram combining the neutrophil-to-lymphocyte ratio and D-dimer level can be applied in the individualized prediction of treatment outcome in patients with advanced gastric cancer.

Long-term Survival, Tolerability, and Safety of First-Line Bevacizumab and FOLFIRI in Combination With Ginsenoside-Modified Nanostructured Lipid Carrier Containing Curcumin in Patients With Unresectable Metastatic Colorectal Cancer.

Background:Colorectal cancer is the third most common malignant disease and the second leading cause of death worldwide. Previous studies showed improved bioavailability and cytotoxicity of ginsenoside-modified nanostructured lipid carrier containing curcumin (G-NLC) in human colon cancer cell lines. This study aimed to evaluate the safety and tolerability with long-term survival rates in patients with colorectal cancer with unresectable metastases after treatment with first-line bevacizumab/FOLFIRI (folinic acid, bolus/continuous fluorouracil, and irinotecan) in combination with a dietary supplement of G-NLC.Methods:This study was a prospective, observational, single-group analysis. The enrolled patients had colorectal cancer with unresectable metastases and were administered bevacizumab and FOLFIRI in combination with daily oral G-NLC as first-line treatment. Overall survival, progression-free survival, tumor response, and adverse events were evaluated.Results:A total of 44 patients were enrolled between 2015 and 2019. The median age was 65 (range 45-81) years and the sex ratio was 31:13 (male:female). The primary tumor locations were the colon (31 patients) and rectum (13 patients). The metastatic sites included, liver only (n = 20), lung only (n = 6), both liver and lung (n = 12), and others (n = 6). The median duration of curcumin supply was 7.9 (range 0.9-16.6) months. The most common grade 3 or higher adverse events were neutropenia (n = 15, 34.1%), followed by nausea (n = 4, 9.1%) and vomiting (n = 4, 9.1%). Within the median follow-up period of 22.8 months, the median overall survival was 30.7 months, and the median progression-free survival was 12.8 months. None of the patients achieved complete response (CR); however, 9 patients showed partial response (PR), and 3 patients underwent conversion surgery.Conclusions:Bevacizumab/FOLFIRI with G-NLC as first-line chemotherapy in patients with colorectal cancer with unresectable metastases presented comparable long-term survival outcomes with acceptable toxicity outcomes. Additional randomized controlled studies are needed to establish definitive conclusions regarding this new regimen for metastatic colorectal cancer.

Trilaciclib and the economic value of multilineage myeloprotection from chemotherapy-induced myelosuppression among patients with extensive-stage small cell lung cancer treated with first-line chemotherapy

Aims Proliferating hematopoietic stem and progenitor cells (HSPCs) are susceptible to chemotherapy-induced damage, resulting in myelosuppressive adverse events (AEs) such as neutropenia, anemia, and thrombocytopenia that are associated with high health care costs and decreased quality of life (QoL). In this study, a trial-based cost-effectiveness analysis was performed to help assess the economic impact of administering trilaciclib, a myeloprotective therapy that protects multilineage HSPCs from chemotherapy-induced damage, prior to standard first-line chemotherapy, using data from a pivotal Phase II study of trilaciclib in the setting of extensive-stage small cell lung cancer (ES-SCLC, NCT03041311). Method The aim of this study was to assess the cost-effectiveness of administering trilaciclib prior to chemotherapy versus chemotherapy alone among patients with ES-SCLC from a United States payer perspective. Data on the rate and frequency of myelosuppressive AEs and health utility were derived from the pivotal study of trilaciclib. Costs of managing myelosuppressive AEs and costs of chemotherapy treatment were sourced from published literature. Outcomes included the number of myelosuppressive AEs, costs (in 2021 US dollars), quality-adjusted life-years (QALYs), incremental cost, incremental QALY, and an incremental cost-effectiveness ratio. Results Administering trilaciclib prior to chemotherapy was associated with a reduction in neutropenia (82%), febrile neutropenia (75%), anemia (43%), and thrombocytopenia (96%) compared with chemotherapy alone. Additionally, trilaciclib prior to chemotherapy was cost-saving compared with chemotherapy alone ($99,919 vs $118,759, respectively) and associated with QALY improvement (0.150 vs 0.145, respectively). Probabilistic sensitivity analyses showed 58% of iterations projecting cost savings and QALY improvement with trilaciclib. Conclusions The findings suggest that the use of trilaciclib prior to first-line chemotherapy in patients with ES-SCLC can be cost-beneficial owing to fewer myelosuppressive AEs and lower costs, together with a favorable QoL profile.

The importance of choosing the right strategy to treat small cell carcinoma of the cervix: a comparative analysis of treatments

BackgroundStandard treatments for small cell carcinoma of the cervix (SCCC) have not been established. In this study, we aimed to estimate the optimal treatment strategy for SCCC.MethodsThis was a multicenter retrospective study. Medical records of patients with pathologically proven SCCC treated between 2003 and 2016 were retrospectively analyzed. Overall survival (OS) was plotted using the Kaplan-Meier method. Log-rank tests and Cox regression analysis were used to assess the differences in survival according to stage, treatment strategy, and chemotherapy regimen.ResultsData of 78 patients were collected, and after excluding patients without immunohistopathological staining, 65 patients were evaluated. The median age of the included patients was 47 (range: 24–83) years. The numbers of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stages I-IIA, IIB-IVA, IVB were 23 (35%), 34 (52%), and 8 (12%), respectively. Of 53 patients who had undergone chemotherapy, 35 and 18 received SCCC and non-SCCC regimens as their first-line chemotherapy regimen, respectively. The 5-year OS for all patients was 49%, while for patients with FIGO stages I-IIA, IIB-IVA, IVB, it was 60, 50, and 0%, respectively. The 5-year OS rates for patients who underwent treatment with SCCC versus non-SCCC regimens were 59 and 13% (p < 0.01), respectively. This trend was pronounced in locally advanced stages. Multivariate analysis showed that FIGO IVB at initial diagnosis was a significant prognostic factor in all patients. Among the 53 patients who received chemotherapy, the SCCC regimen was associated with significantly better 5-year OS in both the uni- and multivariate analyses.ConclusionOur results suggest that the application of an SCCC regimen such as EP or IP as first-line chemotherapy for patients with locally advanced SCCC may play a key role in OS. These findings need to be validated in future nationwide, prospective clinical studies.

Getting the MOST out of follow-up: a randomized controlled trial comparing 3 monthly nurse led follow-up via telehealth, including monitoring CA125 and patient reported outcomes using the MOST (Measure of Ovarian Symptoms and Treatment concerns) with routine clinic based or telehealth follow-up, after completion of first line chemotherapy in patients with epithelial ovarian cancer

BackgroundPhysical symptoms, anxiety, depression, fear of recurrence, sexual dysfunction, and social withdrawal are common in women after treatment for ovarian cancer. Most patients would like and need help dealing with...

Outcome of Postchemotherapy Residual Disease in Extracranial Germ Cell Tumor in Children: Experience of a Tertiary Care Center.

The aim was to review outcome with residual disease at the end of first line chemotherapy in patients with extracranial germ cell tumor (GCT) in our resource limited setting. A retrospective analysis of 196 patients with GCT recruited at Shaukat Khanum Memorial Cancer Hospital (SKMCH) from January 2008 to December 2016. Data fields included site, histopathology, stage, risk groups, baseline alpha fetoprotein, beta human chorionic gonadotropin levels, residuum after primary treatment, completeness of surgical excision and outcomes. Data analysis involved quantitative analysis, mean and median calculations, event free survival (EFS) and overall survival (OS) calculations using Kaplan-Meier curves. In 196 included patients, M:F ratio was 1. There were 81 (41.3%) adolescents. Alpha fetoprotein was >10,000 IU/L in 56 (28.6%) patients. Sixty-two (31.6%) patients had extragonadal disease. Most patients (n=137, 69.9%) presented with advanced stage (III/IV). Seventy-six patients had postchemotherapy residual disease (n=59 [78%] with partial response (PR) and 17 [22%] with no response [NR]). Five-year OS was 83% and EFS was 67%. Five-year EFS of patients with complete remission after primary chemotherapy was 85% versus 70% in patients with PR and 6% in those with NR (P=0.001). OS in patients with complete remission, PR and NR was 94%, 87%, and 46%, respectively. All patients with NR progressed or relapsed and 8/17 died. Four patients with normalized tumor marker response were found to have active tumor on resection of postchemotherapy residuum. Patients with postchemotherapy residual disease in pediatric extracranial GCTs, fare better if their residuum is resected compared with those who do not undergo resection.

203P Randomized study of single-agent metronomic versus weekly oral vinorelbine (VNR) as first-line chemotherapy in patients with HR+/HER2- advanced breast cancer

Single-agent chemotherapy (CT) is a valuable option for patients with advanced breast cancer (ABC) and weekly oral VNR is one of the recommended agents. Metronomic VNR increases patient’s exposure to the drug while improving safety. In early studies, minimal toxicity and promising efficacy were observed with metronomic VNR 50 mg thrice weekly (tw). We randomized patients with ABC to receive either metronomic or weekly oral first-line VNR.

497P Correction of geriatric status in patients with metastatic colorectal cancer

Humanity is aging rapidly, about 50% of all human malignancies develop in people over 65 years old. In 2020, the prevalence of colorectal cancer (CRC) in patients over 60 years was 16.3%, mortality – 15.1%. For effective chemotherapy in this group of patients, the correction of geriatric syndromes (CGS) is extremely relevant. The aim of the study is to increase the efficiency of the first-line chemotherapy in patients with metastatic CRC (mCRC) using CGS.

IL-15-induced lymphocytes as adjuvant cellular immunotherapy for gastric cancer.

ObjectivesTo test the antitumor potential of lymphocytes transferred via adoptive cell therapy (ACT) in a mouse model of human gastric cancer (GC), and to evaluate the clinical efficacy and safety of combining lymphocytes as adjuvant therapy with first-line chemotherapy in patients with GC. MethodsWe constructed a human GC xenograft model in sublethally irradiated 6-8-week-old male NCG mice. MKN-45 cells (1 × 106 cells/mouse) were subcutaneously injected into mice's flanks. After tumors had become palpable, we randomized the mice into control, ACTIL-2, and ACTIL-15 groups. Human lymphocytes were then injected into mouse tail veins. In addition, 63 human patients with histologically or cytologically confirmed stage III-IV GC randomly received S-1 + oxaliplatin + ACTIL-15 (combination therapy group) or S-1 + oxaliplatin (chemotherapy group). ResultsIn the mouse study, treatment with ACTIL-15 cells inhibited tumor growth on adoptive transfer, and mice that received ACTIL-15 cells had significantly longer survival rates (p < 0.05, ACTIL-15 vs. ACTIL-2). In the human study, the median survival rate of patients in the combination therapy group was 472days (95% confidence interval [CI], 276-668days), whereas that of patients in the chemotherapy group was 266days (95% CI, 200-332days; p < 0.05). Eleven percent (7/63) of patients had adverse reactions, but these reactions did not interfere with treatment. ConclusionAdoptive transfer of ACTIL-15 cells in a mouse model of GC and in patients with advanced GC treated with S1 + oxaliplatin improved survival rates in both, with an acceptable safety profile.

Combination therapy of bevacizumab with either S-1 and irinotecan or mFOLFOX6/CapeOX as first-line treatment of metastatic colorectal cancer (TRICOLORE): Exploratory analysis of RAS status and primary tumour location in a randomised, open-label, phase III, non-inferiority trial

AimThe TRICOLORE trial previously demonstrated that S-1 and irinotecan plus bevacizumab was non-inferior, based on progression-free survival (PFS), to 5-fluorouracil, leucovorin and oxaliplatin (mFOLFOX6)/capecitabine and oxaliplatin (CapeOX) plus bevacizumab as first-line chemotherapy for metastatic colorectal cancer (mCRC). Overall survival (OS) data were immature at the time of the primary analysis. MethodsIn total, 487 patients from 53 institutions with previously untreated mCRC were randomly assigned (1:1) to receive either mFOLFOX6/CapeOX plus bevacizumab (control group) or S-1 and irinotecan plus bevacizumab (experimental group; 3- or 4-week regimen). The final OS data were analysed from follow-up data collected until 30th September 2017. ResultsWith a median follow-up period of 48.7 months, median survival times were 32.6 and 34.3 months (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.72–1.10, P = 0.293) and median PFS durations were 10.8 and 14.0 months in the control and experimental groups, respectively (HR: 0.86, 95% CI: 0.71–1.04, P < 0.0001 for non-inferiority). In patients with left-sided RAS wild-type tumours, median PFS durations were 11.4 and 16.9 months in the control and experimental groups, respectively (HR: 0.68, 95% CI: 0.48–0.96, P = 0.028). ConclusionS-1 and irinotecan plus bevacizumab resulted in comparable OS and non-inferior PFS with that of mFOLFOX6/CapeOX plus bevacizumab treatment as first-line chemotherapy for patients with mCRC. We recommend the use of S-1 and irinotecan plus bevacizumab as a standard first-line regimen independent of tumour sidedness or RAS status in mCRC. Trial registrationUMIN-CTR: 000007834.

Modified FOLFIRINOX versus gemcitabine plus oxaliplatin as first-line chemotherapy for patients with locally advanced or metastatic cholangiocarcinoma: a retrospective comparative study

BackgroundGemcitabine plus platinum as the first-line chemotherapy for cholangiocarcinoma (CCA) has limited efficacy. The aim of this study was to evaluate the effectiveness of modified FOLFIRINOX (mFOLFIRINOX) compared to that of gemcitabine plus oxaliplatin (Gemox) for patients with locally advanced or metastatic CCA.MethodsFrom January 2016 to December 2019, consecutive patients who were diagnosed with locally advanced or metastatic CCA were treated with either mFOLFIRINOX or Gemox as a first-line chemotherapy. The main endpoint was Progression free survival (PFS). The second endpoints were Overall survival (OS), Disease control rate (DCR) and incidence of severe toxicity (grade 3–4). Tumors were evaluated at baseline and thence every 4–6 weeks. The study was designed and carried out in accordance with the principles of the declaration of Helsinki, approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine (XHEC-D-2020-154) and registered with ClinicalTrials.gov, number NCT04305288 (registration date: 12/03/2020).ResultsOf 49 patients in this study, 27 were in the FOLFIRINOX regimen group and 22 in the Gemox regimen group. There were no significant differences between groups in baseline characteristics. The DCR was 77.8% in the mFOLFIRINOX group and 63.5% in the Gemox group. The corresponding median PFS was 9.9 months (95% confidence interval [CI], 7.3–12.4) in the mFOLFIRINOX group versus 6.4 months (95% CI,3.6–9.2, p = 0.040) in the Gemox group. The corresponding median OS was 15.7 months (95% CI, 12.5–19.0) versus 12.0 months (95% CI, 9.3–14.8, p = 0.099). Significantly more grade 3–4 vomiting occurred in the mFOLFIRINOX than the Gemox groups (7 (25.9%) vs 1 (4.5%), p = 0.044).ConclusionsFirst-line mFOLFIRINOX offered more promising results in patients with advanced or metastatic CCA.

P-16 How does reinduction of first-line chemotherapy in patients with metastatic colorectal cancer impact outcomes? Experience from the University Hospital for Tumors, Zagreb, Croatia

Evidence related to reinduction of first-line therapy after maintenance in metastatic colorectal cancer (mCRC) patients remains insufficient. Only about 40% of our patients receive second-line therapy, raising concerns about the efficacy of this treatment plan. We hypothesized that prolongation of first-line therapy may affect patient's probability of receiving second-line therapy and therefore, we aimed to investigate how reinduction and prolongation of the first-line therapy affects overall survival (OS).

Comparison of first line chemotherapy regimens for advanced soft tissue sarcoma: a network meta-analysis

The best first line chemotherapy regimen for advanced soft tissue sarcoma (ASTS) remains inconclusive. Here, we aimed to find the best first line chemotherapy regimen by performing a network meta-analysis. Regimens were compared in terms of overall survival (OS), overall response rate(ORR), progression free survival (PFS), and toxicity. Twenty-eight eligible trials with a total of 6928 patients were included. EC (epirubicin + cisplatin) was considered as the better regimen for advanced STS with probability of 61.9% in terms of OS. However, this regimen only have been evaluated in a single small trial and tend to have more hematological toxicities than doxorubicin. No regimen was superior to doxorubicin with significant statistical difference in terms of PFS and ORR, even aldoxorubicin behaved better than doxorubicin in the network analysis. Collectively, doxorubicin still can be selected preferentially for the first line chemotherapy for patients.