Second-line Chemotherapy Research Articles

Efficacy of poly (ADP-ribose) polymerase inhibitors monotherapy and the impact to subsequent platinum-based chemotherapy in breast cancer susceptibility genes1/2-mutated ovarian cancer patients with secondary platinum-sensitive relapse

BackgroundThe therapeutic effect of poly (ADP-ribose) polymerase inhibitors (PARPi) monotherapy compared with platinum-based chemotherapy, and the impact to subsequent platinum-based chemotherapy after PARPi resistance were inconclusive in breast cancer susceptibility genes (BRCA)1/2-mutated ovarian cancer patients with secondary platinum-sensitive relapse.MethodsBRCA1/2-mutated patients with secondary platinum-sensitive relapse included in this study did not receive any maintenance regimen after first- and second-line platinum-based chemotherapy, and the secondary platinum-free interval (PFI) was more than 6 months. Patients in study group were treated with PARPi monotherapy until disease progression, and patients in control group were treated with platinum-based chemotherapy without restriction. Progression-free survival (PFS) was defined as the time from third-line therapy to disease progression or death, PFS2 was defined as the time from platinum-based chemotherapy after PARPi resistance to next subsequent therapy or death. Post-recurrence survival (PRS) refers to the survival time after secondary platinum-sensitive relapse.ResultsA total of 119 patients were retrospectively analyzed, including 71 (59.7%) in study group and 48 (40.3%) in control group. The objective response rate (ORR: 77.5% vs. 80.0%, p=0.766) and PFS (median: 11.2 vs. 11.0 months, p=0.962) were comparable. The benefit of subsequent platinum-based chemotherapy after PARPi resistance was more pronounced in patients with PARPi treatment for more than 12 months (median PFS2: 8.6 vs. 4.3 months, p=0.040). PARPi monotherapy had no adverse effect on PRS compared with platinum-based chemotherapy (median PRS:41.2 vs. 42.8 months, p=0.323). Compared to patients in control group who had never received PARPi, PARPi monotherapy (median PRS: 41.2 vs. 33.7 months, p=0.019) and post-line treatment with PARPi in the control group (median PRS: 48.1 vs. 33.7 months, p=0.002) could prolong PRS for patients with secondary platinum-sensitive relapse.ConclusionsPARPi monotherapy was similar to platinum-based chemotherapy for BRCA1/2-mutated ovarian cancer patients with secondary platinum-sensitive recurrence, and could improve prognosis.

Safety and efficacy of amrubicin with primary prophylactic pegfilgrastim as second-line chemotherapy in patients with small cell lung cancer.

Amrubicin (AMR) regimens have shown efficacy as second-line treatment in patients with small cell lung cancer (SCLC); however, adverse events such as febrile neutropenia (FN) sometimes preclude their use. Further, the safety and efficacy of AMR with primary prophylactic pegfilgrastim (P-PEG) have not been sufficiently evaluated. In this study, we evaluated the safety and efficacy of AMR with or without P-PEG as second-line chemotherapy for SCLC. We retrospectively reviewed patients with SCLC who received AMR as second-line chemotherapy at Shizuoka Cancer Center, between December 2014 and November 2021. Based on presence/absence of P-PEG in their regimen, patients (n = 60) were divided into P-PEG (n = 21) and non-P-PEG groups, and their clinical outcomes were evaluated. Median of AMR treatment cycles was five (range: 1-39 cycles) in P-PEG group and four (range: 1-15 cycles) in non-P-PEG group. The incidence of FN (4.8% vs. 30.8%; p = 0.02) and AMR dose reduction because of adverse events (4.8% vs. 25.6%; p = 0.08) were lower in the P-PEG group than in the non-P-PEG group. The objective response rates were 52.4% and 30.8%, and median progression-free and overall survival were 4.7 and 3.0 months, and 9.6 and 6.8 months, in the P-PEG and non-P-PEG groups, respectively. AMR with P-PEG as second-line chemotherapy for SCLC reduced the incidence of FN at a maintained AMR dose intensity and was associated with favorable tumor responses and survival outcomes. P-PEG should be considered for patients treated with AMR for SCLC including refractory relapsed SCLC.

Metastatic castration-resistant prostate cancer-what are rational sequential treatment options?

In advanced prostate cancer, disease progression during ongoing androgen deprivation therapy (ADT) is referred to as castration-resistant prostate cancer (CRPC). Various therapeutic modalities are available for its treatment, including endocrine therapy, chemotherapy, poly (ADP-ribose) polymerase [PARP] inhibition, radionuclide therapy, and radioligand therapy. This review outlines practical aspects and considerations regarding treatment sequencing in mCRPC. The findings are based on existing prospective phase3studies that have demonstrated clinically relevant and statistically significant benefits in radiographically progression-free and/or overall survival. Sequential therapy, aside from numerous patient-specific factors, depends on the treatment patients received in the hormone-sensitive prostate cancer (mHSPC) setting. Following pretreatment with ADT alone or ADT plus docetaxel in the mHSPC context, additional endocrine therapy is the standard approach. In the event of progression under combined endocrine therapy initiated in the mHSPC setting, docetaxel currently serves as the standard for the majority of patients. Patients who received triplet therapy as apretreatment in the mHSPC scenario can be treated with radioligand therapy or second-line chemotherapy. Various active and well-tolerated treatment options are available for patients with metastatic castration-resistant prostate cancer (mCRPC). The choice of therapy is primarily determined by previous treatments, but many other individual factors are also taken into consideration.

Prior treatment with oxaliplatin-containing regimens and higher total bilirubin levels are risk factors for neutropenia and febrile neutropenia in patients with gastric or esophagogastric junction cancer receiving weekly paclitaxel and ramucirumab therapy: a single center retrospective study

BackgroundWeekly paclitaxel + ramucirumab (wPTX + RAM) therapy is recommended as the standard second-line chemotherapy regimen for unresectable advanced/recurrent gastric cancer (GC) or esophagogastric junction cancer. Recent subgroup analysis of the RAINBOW trial revealed a higher frequency of severe neutropenia due to wPTX + RAM in Japanese compared to Western patients. However, no risk factors for severe neutropenia have been identified.MethodsThis retrospective observational study included patients with advanced/unresectable gastric or esophagogastric junction cancer who received wPTX + RAM after failure to respond to platinum and fluoropyrimidine doublet chemotherapy between June 2015 and April 2020. We conducted multivariable logistic regression analyses to identify the risk factors associated with grade 4 neutropenia and febrile neutropenia (FN). In addition, we investigated the relationship between the number of risk factors and overall survival (OS) and progression-free survival (PFS).ResultsAmong 66 patients who met the inclusion criteria, grade 4 neutropenia and FN occurred in 21 (31.8%) and 12 (18.2%) patients, respectively. Prior treatment with oxaliplatin-containing regimens was identified as an independent risk factor for developing grade 4 neutropenia (odds ratio (OR) 20.034, 95% confidence interval (95% CI) 3.216–124.807, P = 0.001). Total bilirubin of > 1.5 mg/dL (OR 31.316, 95% CI 2.052–477.843, P = 0.013) and prior treatment with oxaliplatin-containing regimen (OR 12.502, 95% CI 1.141–137.022, P = 0.039) were identified as independent risk factors for developing FN. Next, we classified patients with 0, 1, 2 risk factor(s) as RF-0, RF-1, and RF-2 subgroups, respectively, and compared the PFS and OS among the three subgroups. PFS was not significantly different among the three subgroups, whereas OS was significantly shorter in the RF-2 subgroup (median 1.4 month, 95% CI 0.0–5.3 month) than in the RF-0 subgroup (median 10.2 month, 95% CI 6.8–13.5 month, P < 0.01 vs RF-2) and RF-1 subgroup (median 13.3 month, 95% CI 10.9–15.7 month, P < 0.01 vs RF-2).ConclusionsCareful monitoring for grade 4 neutropenia and FN is needed for patients receiving wPTX + RAM therapy who have a history of treatment with oxaliplatin-containing regimens and higher total bilirubin levels.

Advances in The Treatment of Intrahepatic Cholangiocarcinoma-ICLCA

Intrahepatic cholangiocarcinoma (iCLCA) is a fatal hepatobiliary tumor becoming more common. For a long time, it was largely ignored as an uncommon cancer and commonly misdiagnosed as carcinoma of unidentified origin; nonetheless, significant clinical and research attention has been dedicated to it lately. First-line (gemcitabine and cisplatin), second-line (FOLFOX), and adjuvant (capecitabine) systemic chemotherapy is the accepted standard of treatment. iCLCA is genetically unique from hepatocellular carcinoma, with multiple targetable genetic abnormalities reported to be far. Indeed, FGFR2, NTRK fusions, IDH1, and BRAF targetable mutations have been thoroughly studied, and clinical evidence on pharmacologically targeting these oncogenic drivers is emerging. In addition, the role of immunotherapy has been investigated and is a hot topic. There is a need for therapeutic interventions for these ailments. Our review focuses on Intrahepatic cholangiocarcinoma, cholangiocarcinoma, Extrahepaticcholangiocarcinoma, Vascular Epidermal Growth Factor, IDH inhibitors, and Liver Cancer.

Initial Experiences in Adolescents and Young Adults with T-Cell Acute Lymphoblastic Leukemia/Lymphoma Treated with the Modified BFM 2002 Protocol in a Resource-Constrained Setting

T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) in adolescents and young adults (AYAs) is a clinically aggressive malignancy and life-threatening at diagnosis. Intensive chemotherapy protocols, inspired by the Berlin-Frankfurt-Münster (BFM) regimen, along with central nervous system (CNS) prophylaxis, have achieved a 75 to 85% 5-year disease-free survival rate. However, in cases of marrow and CNS relapses, second-line chemotherapy is usually ineffective. This study aimed to assess the safety and efficacy of the BFM 2002 protocol and to correlate clinical profiles and prognostic factors with survival outcomes in AYA T-ALL/LBL patients. We retrospectively analyzed data from T-ALL/LBL patients treated at the Department of Medical Oncology, Sri Aurobindo Institute of Medical Sciences (SAIMS), Indore, between 2018 and 2021. Twenty-one patients aged 15 to 29 years were studied for their clinical course and laboratory parameters over 36 months. Diagnosis and risk stratification were performed following the guidelines of the BFM 2002 protocol. All patients received treatment and monitoring according to this pediatric-inspired protocol. The median age of the patients was 17 years (range: 15–28 years). Eleven patients presented with mediastinal lymph node enlargement, 10% exhibited CNS involvement, and none had testicular involvement. Eleven patients had marrow blasts greater than 25%, indicative of acute lymphoblastic leukemia. All 21 patients were treated according to the intensive modified BFM 2002 protocol and achieved morphological remission after a median follow-up of 24 months (range: 18–36 months). Seventeen patients achieved minimal residual disease (MRD) negativity post-induction. MRD at day 33 showed a significant association with the probability of disease relapse (p = 0.0015). There were five deaths (24%), one due to toxicity and four due to relapse. The study recorded an 18-month overall survival of 76%. These results were achieved despite financial constraints. Data were entered into a spreadsheet, and statistical analysis was performed using IBM SPSS version 23. Continuous data are presented as ranges and medians, while categorical variables are shown as percentages and numbers. A chi-squared test for association, with a significance level set at p &lt; 0.05, was conducted as indicated. AYA T-ALL/LBL requires intensive treatment regimens. With biological characterization of LBL/ALL and close therapy monitoring, encouraging outcomes can be achieved even in resource-limited settings.

103P Individual patient data (IPD) meta-analysis of randomised trials to compare efficacy of second-line fluoropyrimidine-based chemotherapy in advanced biliary tract cancer (BTC)

103P Individual patient data (IPD) meta-analysis of randomised trials to compare efficacy of second-line fluoropyrimidine-based chemotherapy in advanced biliary tract cancer (BTC)

PD-1-expressing macrophages and CD8 T cells are independent predictors of clinical benefit from PD-1 inhibition in advanced mesothelioma

BackgroundFew tissue biomarkers exist to date that could enrich patient with cancer populations to benefit from immune checkpoint blockade by programmed cell death protein 1/ligand-1 (PD-/L-1) inhibitors. PD-L1 expression has...

Algorithme thérapeutique des CBNPC sans mutation addictive: Algorithm of NSCLC management outside oncogenic addiction

The development of immunotherapy in first-line therapy with anti-PD-1 and anti-PD-L1 has changed the first line treatment algorithm of advanced NSCLC. The anti-PD-(L)1 pembrolizumab, atézolizumab and cemiplimab clearly improve the overall survival in NSCLC with high PD-L1 expression (≥ 50% of tumour cells), comparatively to cytotoxic chemotherapy. Combinations of anti-PD(L)-1 to platinum-based chemotherapy are superior to chemotherapy alone, regardless of PD-L1 level of expression. They represent the 1st line gold-standard when PD-L1 is expressed in less than 50 % of tumour cells and might reduce the risk of early disease progression in comparison with pembrolizumab when PD-L1 ≥ 50%. The room for anti-CTLA-4 + anti-PD(L)-1 combinations which are not available in France remains to be established. Second-line treatment is currently based on chemotherapy, with a platinum-based doublet for patients treated in first line by pembrolizumab alone, and standard second-line chemotherapy options for patients treated by chemotherapy-immunotherapy combinations, i.e. docétaxel regardless of histology or pemetrexed for non-squamous cell carcinoma when not used in first line. Addition of an antiangiogenic agent to docetaxel only achieved a modest improvement of overall survival but neither nintedanib, nor docetaxel is available in France. Combination of paclitaxel and bevacizumab is also an option. Immunotherapy still benefits only a minority of patients whose identification is imperfect, underscoring the need for new strategies based on ne‹ combination amplifying the anti-tumour immune response as well as understanding the mechanisms of resistance to treatment in order to improve these results. Supportive care remains crucial for all patients from the time of diagnosis.1877-1203/© 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Les CBNPC de stades avancés hors addiction oncogénique : les traitements systémiques de deuxième ligne: Advanced stage NSCLC excluding oncogenic addiction: second-line systemic treatments

The emergence of immunotherapy as the cornerstone of first line therapy in advanced stage Non-Small Cell Lung Cancer (NSCLC), without oncogenic driver, has led to change the treatment algorithm of second line, which was previously and mainly based on anti-PD(L)-1 given as a single agent. Second-line treatment is currently based on chemotherapy, with a platinumbased doublet for patients treated in first line by pembrolizumab alone, and standard second-line chemotherapy options for patients treated by chemotherapy-immunotherapy combinations, i.e. docétaxel regardless of histology or pemetrexed for non-squamous cell carcinoma when not used in first line. Addition of an antiangiogenic agent to taxane only achieved a modest improvement of overall survival. The future of second line treatment would require a better knowledge and understanding of resistance mechanisms to anti-PD(L)-1, and randomized phase III clinical trials, in order to optimize therapeutic options, including or not a rechallenge to an immunotherapy, targeting to restore anti-tumour immune response. Antibody drug-conjugate seem to be also a promising approach in this setting.1877-1203/© 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.

2093P Bioelectrical Impedance phase angle and obesity as a prognostic indicator in metastatic gastric cancer patients receiving second-line chemotherapy

2093P Bioelectrical Impedance phase angle and obesity as a prognostic indicator in metastatic gastric cancer patients receiving second-line chemotherapy

CNS Control after First-Line Osimertinib in Patients with Metastatic EGFR-Mutant NSCLC

Although osimertinib (osi) has excellent intracranial activity in EGFR-mutant metastatic non-small cell lung cancer (NSCLC), there is no consensus regarding whether to continue osi for central nervous system (CNS) control with second-line chemotherapy (chemo) at the time of systemic progression. We aimed to compare CNS outcomes after first-line osi in patients receiving second-line chemo with or without continuation of osi. We retrospectively reviewed patients with EGFR-mutant NSCLC with brain metastases (BrM) at the time of initiating first-line osi who experienced progression and started second-line chemo. Cumulative incidence of local and distant CNS progression, and extracranial (EC) progression was calculated from time of second-line chemo initiation with death as a competing risk. Overall survival (OS) was analyzed using Kaplan-Meier. We included 52 patients with a median follow up of 9.6 months (range 0.4-36.4). Median OS and CNS progression-free survival (PFS) from the time of starting second-line chemo was 12.5 months (95% CI 8.1-16.9), and 5.3 months (95% CI 3.35-7.26), respectively. The 1-year cumulative incidence of local, distant CNS progression, any CNS progression, and EC progression was 14.4% (95% CI 4.5-24.2), 42.8% (95% CI 22.8-56.8), 42.8% (95% CI 22.8-56.8) and 66.8% (95% CI 53.5-80.2), respectively. After progression on first-line osi, 25 (48.1%) and 27 patients (51.9%) continued and discontinued osi, respectively. Patients who continued osi had significantly higher BrM burden than those who did not, with 17 (68%), 3 (12%), and 5 (20%) versus 26 (96%), 0, and 1 (3.7%) patient having <10 or >11 parenchymal brain lesions, or leptomeningeal disease (LMD) at the time of second line therapy, respectively (p<0.01). In those who continued osi vs those who did not, median OS (10.8 vs 12.5 months; p = 0.37), median intracranial PFS (5.3 vs 4.8 months; p = 0.99), 1-year cumulative incidence of local (8.4% versus 20 % p = 0.26), and 1-year distant CNS progression (24.8% vs 60%; p = 0.08) was not significantly different. CNS complications such as symptomatic, hospitalizations, and steroid initiation for CNS disease, and progression of LMD were not significantly different between the two groups. Eventually, 10 patients underwent salvage RT post first-line osi and median time to salvage RT was 7.8 months (range 2-9.4). Of patients who underwent salvage RT, 2 patients (20%) had continued osi with second-line chemo. Twelve patients (44.4%) who did not continue osi eventually re-started osi for progressive disease. Patients who continued osi had significantly higher BrM tumor burden. Despite these patients being at higher risk for CNS progression, time to CNS progression and incidence of CNS complications were not significantly different in the two cohorts. Patients who discontinued osi were more likely to undergo salvage RT. Continuation of osi may allow patients to defer salvage RT.

Outcomes of Consolidative Thoracic Radiation within First-Line Chemoimmunotherapy in Extensive-Stage Small-Cell Lung Cancer: Results from a Single Cancer Center

Thoracic radiation (TRT) benefits local control undoubtedly and survival with some minor controversy in extensive-stage small-cell lung cancer (ES-SCLC) patients undergoing radiotherapy in the chemoradiotherapy era. However, whether TRT could further enhance the benefit of immune checkpoint inhibitors (ICIs) maintenance on outcomes in the immunotherapy era is still unclear. This study aims to investigate the role of consolidative TRT in ES-SCLC patients receiving first-line chemoimmunotherapy followed by immunotherapy maintenance. Outcomes of patients who were treated with first-line chemo-immunotherapy followed by ICIs maintenance for ES-SCLC were reviewed. Based on TRT or not, patients were allocated to TRT group or non-TRT group. Progression-free survival (PFS), overall survival (OS) and local-recurrence free survival (LRFS) were calculated by the Kaplan-Meier method and compared by log-rank test. A total of 100 patients with no progressive disease after 4 cycles of chemotherapy were retrospectively analyzed between January 2020 and December 2021 and were allocated into TRT group (n = 47) and non-TRT group (n = 53). The median follow-up time was 20.3 months. The median PFS and OS in TRT were 9.1 months and 21.8 months, versus 8.8 months (p = 0.93) and 24.3 months (p = 0.63), respectively, in non-TRT. ICIs agents consisted of Durvalumab (59.0%) and Atezolizumab (41.0%). The median dose of TRT is 50 Gy (IQR: 45 - 54), while the median interval time from chemotherapy completion to TRT was 31 days (IQR: 12 - 44.5). Only 10 (21.3%) patients terminated ICIs in the period of TRT. The rate of intrathoracic progression after the first-line therapy in TRT significantly decreased compared to that with non-TRT (20.0% versus 55.9%, p = 0.003). The median LRFS time in TRT was not reached, but significantly longer than 10.8 months in non-TRT (HR = 0.27, p < 0.01). Second-line chemotherapy significantly prolonged survival compared to that with chemo-free patients (mOS: 24.5 vs. 21.4 months, p = 0.026). The subgroup analysis showed a trend of patients with brain metastases benefit from TRT (21.8 versus 13.7 months, HR 0.61, p = 0.38) while liver metastases did not (13.3 versus 15.0 months, HR 1.80, p = 0.21). Of 47 patients with TRT, only 10.6% of patients experienced grade 3 radiation-induced pneumonitis, while no grade 4 or 5 adverse events occurred. None of patients experienced grade ≥ 3 treatment-related cardiac events. Consolidative TRT in the period of immunotherapy maintenance followed first-line chemo-immunotherapy did not prolong OS and PFS but increased LRFS in ES-SCLC.

Efficacy of ESHAP versus ICE plus dexamethasone (DICE) as salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma

Objectives To compare the efficacy and side effects of salvage chemotherapy between etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) and ifosfamide, carboplatin and etoposide plus dexamethasone (DICE) for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Methods Medical records of patients with relapsed or refractory DLBCL receiving second-line ESHAP or DICE chemotherapy with or without rituximab from January 2007 to November 2022 were retrospectively reviewed. The primary objective was progression-free survival (PFS). The secondary objectives were overall survival (OS), overall response rate (ORR) and adverse events (AEs). Results Seventy patients were enrolled including 21 patients who received ESHAP and 49 patients who received the DICE regimen. Six patients (28.6%) and 19 patients (38.8%) in the ESHAP and DICE groups underwent ASCT, respectively. The ORR was 47.6% for ESHAP and 53.1% for DICE (p = .67). The two-year PFS was 14.3% for ESHAP and 26.5% for DICE (p = .33) with median PFS of 5 months and 14 months, respectively (hazard ratio 0.74; 95% CI 0.39–1.36, p = .330). The two-year OS was 14.3% for ESHAP and 26.5% for DICE (p = .37) with median OS of 8 months and 19 months, respectively. Patients in ESHAP group have more all-grade renal impairment than DICE group (23.8% vs. 6.1%, p = .047). Discussion and conclusions Efficacy between ESHAP and DICE regimens as salvage chemotherapy for relapsed or refractory DLBCL was not significantly different in terms of two-year PFS, two-year OS and ORR. DICE regimen had less renal AE than ESHAP.

Impact of previous anthracycline therapy in patients with acute myeloid leukemia receiving venetoclax.

Venetoclax (VEN) combination regimens are now recognized as effective against acute myeloid leukemia (AML). However, the prognosis of patients who do not attain a composite complete response (cCR) is extremely poor, and clinical determinants of response remain unknown. Medical records of 57 patients with AML treated with VEN combination regimens from April 2021 to March 2022 at six institutions were retrospectively analyzed. The primary endpoint was cCR, complete remission, or complete remission with incomplete hematologic recovery after one cycle of VEN combination regimen. Five patients had previously relapsed after allogeneic hematopoietic stem cell transplantation (allo-SCT). The treatment regimen was azacitidine-VEN in 48 patients (84%) and low-dose cytarabine-VEN in 9 patients (16%). Thirty patients (53%) achieved cCR after one cycle of a VEN regimen. In univariate analysis, the number of prior chemotherapy regimens, post-allo-SCT relapse, and cytogenetic risk category were associated with a decreased likelihood of achieving cCR. In multivariate analysis, second-line chemotherapy remained a significant predictor of response. Patients who received anthracycline immediately before the VEN regimen had a higher cCR rate than patients who did not receive anthracycline. In this study, prior chemotherapy/allo-SCT and cytogenetic risk were associated with VEN treatment outcomes.

P17.05.A TUMOR-TREATING FIELDS COMBINED WITH SECOND-LINE CHEMOTHERAPY REACHED PROGRESSION FREE SURVIVAL OF 8.33 MONTHS IN CHINESE RECURRENT GLIOBLASTOMA

Abstract BACKGROUND Tumor-treating Fields (TTFields) monotherapy has been approved for recurrent glioblastoma. However, TTFields combined with second-line chemotherapy has not been well studied in China. This study aims to explore the efficacy and safety of such combination therapy for recurrent GBM. MATERIAL AND METHODS This study is a prospective, single-arm, open-label clinical trial (NCT04689087) planning to enroll 40 recurrent supratentorial GBM and use TTFields combined with physician choose second-line chemotherapy. Kaplan-Meier survival curve was used to estimate PFS, OS and survival rate. Safety of the combined treatment was assessed by AE incidence. RESULTS Thirty-four recurrent supratentorial GBM patients was enrolled from April 2019 to February 2023. The average age was 51.9 and median KPS score was 80. Seventy-seven percent (26/34) of them underwent total resection surgery and 2.9% (1/34) only experienced biopsy. Eighty-eight percent (30/34) of patients started TTFields when they were first diagnosed as recurrence, while 12% (4/34) patients started TTFields at their second time recurrence or latter, and average compliance of TTFields was 85.5%. As for molecular biomarkers, 47.1% (16/34) patients were MGMT methylated and 38.2% (13/34) were TERT mutant. Since the study initiated in 2019, one IDH-mutant patients were also enrolled. Second-line chemotherapy was combined with antiangiogenic therapy in 47.1% (16/34) patients. The median follow-up period was 8.33 months. Median PFS of these 34 recurrent GBM patients was 8.33(95% CI 4.72-11.95) months, but median OS was not reached. Six months PFS rate was 56.8% (EF-11 historical data of physicians choose chemotherapy was 15.1%) and 6 months OS rate was 74.8%. Two thirds of patients experienced grade 1 or 2 skin adverse events which can be relieved by topical corticosteroids. CONCLUSION TTFields combined with second-line chemotherapy showed favorable efficacy and safety in Chinese recurrent GBM patients.

P11.03.A DOES REGULAR SURVEILLANCE IMAGING IMPROVE SURVIVAL IN GLIOBLASTOMA? RESULTS FROM A NATIONAL, MULTI-CENTRE COHORT STUDY (INTERVAL-GB)

Abstract BACKGROUND Glioblastoma is the most common malignant primary brain tumour in adults and is usually incurable. Post-operative magnetic resonance imaging (MRI) is used to assess extent of resection, and subsequent follow-up MRI is used to monitor response to treatment and to detect progression. The benefit of regular, scheduled follow-up MRI on patient management and outcomes is unclear. MATERIAL AND METHODS In this multi-centre, retrospective observational cohort study we included patients with a histopathologically confirmed glioblastoma, operated between August 31, 2018 and February 1, 2019 who received any adjuvant oncological treatment. Follow-up MRI schedules, indications, and clinical outcomes were collected. The primary objective was to investigate the follow-up MRI surveillance practice after surgery for glioblastoma and assess compliance with recommendations from the National Institute for Health and Care Excellence (NICE) (Post-operative scan &amp;lt;72 hrs, MRI every 3-6 months). The secondary objectives were to determine indications for MRI scans and the association on overall survival (OS) and progression-free survival (PFS). RESULTS 754 patients, with a median age of 63 years (range: 21-84) from 26 neuro-oncology centres were included. Most patients had post-operative MRI within 72 hours of surgery (88.1%, N=407/462). The median number of subsequent follow-up MRI was 1 (Interquartile range 0-4). 28.1% of patients had follow-up MRI in accordance with NICE recommendations (N=212/754). Patients in this group were more likely to receive second-line chemotherapy (28.6% vs 19.5%, P=0.009). The median follow-up period was 10.5 months (IQR 5.3-19.4 months). Median overall survival was 15.1 months (95% CI 12.9-17.3) in the scheduled MRI group and 9.1 months (95% CI 7.8-10.4) in the non-compliant group. On multivariable cox regression analysis, regular, scheduled MRI was independently associated with longer overall survival (HR 1.67, 95% CI 1.33-2.10, P&amp;lt;0.001), but not PFS (HR 1.20, 95% CI 0.98-1.47, P=0.074). Patients with progression first detected on scheduled imaging had a significantly longer OS (18.4 vs 15.6 months, P=0.013) and PFS (9.9 months vs 7.9 months, P=0.041). CONCLUSION Following regular scheduled surveillance follow-up MRI for glioblastoma is associated with longer overall survival. Prospective trials are needed to determine whether regular or symptom-directed MRI influences survival outcomes and quality of life.

Evaluation of hypofractionated adaptive radiotherapy using the MR Linac in localised pancreatic cancer: protocol summary of the Emerald-Pancreas phase 1/expansion study located at Oxford University Hospital, UK

IntroductionOnline adaptive MR-guided radiotherapy allows for dose escalation to pancreatic cancer while sparing surrounding critical organs. We seek to evaluate the safety of delivering hypofractionated five-fraction, three-fraction and single-fraction MR-guided...

Vedolizumab as Rescue Therapy in Carboplatin-Gemcitabine-Induced Triggered Acute Severe Ulcerative Colitis Flare-Up

Approximately 20% of patients with ulcerative colitis (UC) develop acute severe UC (ASUC), for which intravenous systemic steroid therapy and possibly infliximab-based rescue therapy are generally imposed. However, there are no significant guideline recommendations on ASUC regarding vedolizumab as an alternative in this setting. A case report was presented where a patient with steroid-dependent UC developed ASUC induced by second-line chemotherapy. Treatment with intravenous methylprednisolone was imposed, but there was no reduction in bowel movements in the days following admission. Rescue therapy with infliximab was contraindicated because of the oncologic history. Surgical consultation, contraindicated colectomy, and administration of vedolizumab 300 mg were initiated. After infusion with vedolizumab, there was a significant reduction in bowel movements starting the day after infusion until normalisation of bowel movements within three days and the concomitant normalisation of inflammatory indices. The patient is currently in clinical remission, on therapy with vedolizumab 108 mg subcutaneously every two weeks, and is in oncologic follow-up for pulmonary neoplasm. This case highlights the novel potential of vedolizumab as a possible rescue therapy in ASUC, especially in special populations, where it may offer a better safety profile. Although cyclosporine and infliximab still represent the mainstays of salvage therapy for steroid-refractory ASUC, new therapeutic agents may also be effective, such as vedolizumab, ustekinumab, and anti-Janus kinase agents.

Comparing effectiveness and safety of paclitaxel plus raltitrexed vs. paclitaxel alone in second-line palliative chemotherapy for metastatic gastric adenocarcinoma: A randomized phase II clinical trial.

Paclitaxel (P) is a standard second-line chemotherapy in the treatment of advanced gastric cancer. This study compared the clinical outcome of a paclitaxel plus raltitrexed (RP) regimen as second-line treatment in metastatic gastric cancer (MGC) patients. An open, randomized, multi-center phase II clinical trial was conducted involving 148 patients who were randomly assigned and treated with RP [raltitrexed (3 mg/m2 on day 1) and paclitaxel (135 mg/m2 on day 1 every 3 weeks)] or P [paclitaxel (135 mg/m2 on day 1 every 3 weeks)] as 2nd-line chemotherapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the overall response rate (ORR), overall survival (OS), and safety. PFS had a tendency to be prolonged with RP compared to P (2.7 months vs. 1.7 months; P = 0.148). OS was also prolonged with RP compared to P (10.2 months vs. 6.1 months; P = 0.140). The ORR was equal in the RP and P groups (6.8% and 4.0%; P = 0.72). The disease control rate (DCR) in the RP and P groups was 56.2% and 36.0%, respectively. Grade 3-4 treatment-related adverse events occurred in 36.2% (RP) and 28.2% (P) of patients. Frequent grade 3-4 toxicities for RP and P were neutropenia (11.0% and 4.0%), anemia (1.4% and 4.0%), and thrombocytopenia (1.4% and 5.3%), and all grades of peripheral neurotoxicity (12.3% vs. 17.3%). All grades of hepatic toxicity were demonstrated for the RP and P groups based on elevated aminotransferase levels (27.4% and 14.1%). Subgroup analysis shows if MGC was combined with ascites or peritoneal involvement, the OS of the RP regimen was longer (P = 0.05). Second-line palliative chemotherapy with RP was shown to prolong the PFS and OS, especially among patients with ascites or peritoneal involvement, which warrants confirmation using larger sample studies.