Completion Of First-line Chemotherapy Research Articles

Outcome analysis of autologous stem cell transplantation in refractory and relapsed Hodgkin lymphoma: Insights from a North African single-institution study.

172 Background: The standard therapy for primary refractory or relapsed Hodgkin lymphoma (HL) involves the administration of high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT). Nevertheless, several risk factors may influence survival outcomes. We assessed outcomes of patients in this setting who underwent HDC/ASCT by performing survival analysis and studying prognostic factors affecting survival. Methods: We conducted a single-institution retrospective analysis of patients with relapsed/refractory HL who received HDC/ASCT between January 2018 and December 2022. Patients’ status evaluation before ASCT was performed by Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) Scan and Computed Tomography (CT) Scan. The used conditioning regimen was BEAM (Carmustine, Etoposide, Cytarabine, and Melphalan). The primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival analysis was performed using the Kaplan-Meier method, and survival differences between groups were assessed using the Log-Rank test. Results: Thirty-five patients diagnosed with relapsed/refractory HL were included in the study. Among them, 26 patients (74%) had refractory disease, while 9 patients (26%) relapsed following completion of first-line chemotherapy. All patients were treated with HDC/ASCT. Prior to ASCT, 30 patients underwent assessment using FDG-PET Scan, while CT Scan was employed for evaluation in 5 patients. Twenty-three patients (66%) were in complete remission, 8 patients (23%) were in partial remission, and 4 patients (11%) had progressive disease. With a median follow-up of 24.36 months after transplantation, 28 patients (80%) were in remission, 6 patients (17%) had disease progression, and one patients died of septic shock. The 2-year PFS and OS rates for the total population were 85.4% and 97.1%, respectively. Response to first-line chemotherapy did not have a substantial impact on prognosis, as evidenced by a 2-year PFS rate of 76.2% vs. 88.9% (p=0.88) and a 2-year OS rate of 100% vs. 96.2% (p=0.56) for patients with relapsed and refractory disease, respectively. The 2-year PFS and OS rates for patients receiving autograft during complete remission, partial response, and tumor progression were 93.8% vs. 87.5% vs. 50% (p=0.005), respectively; and 95.7% vs. 100% vs. 100%, respectively (p=0.77). Patients who had negative pre-transplant PET-Scans demonstrated a 2-year PFS rate of 92.9% vs. 64.8% for those with positive PET-scans (p=0.004). Conclusions: The findings of our study affirm the established practice of HDC/ASCT for individuals facing relapsed/refractory HL. The disease status at transplant and the pre-transplant PET-Scan status prove to be crucial factors in predicting patients’ outcomes, while response to first-line chemotherapy did not influence prognosis.

Treatment patterns and clinical outcomes of extensive stage small cell lung cancer (SCLC) in the real-world evidence ESME cohort before the era of immunotherapy

BackgroundSmall cell lung cancer (SCLC) is a highly aggressive entity of lung cancer with tendency toward early recurrence after first-line treatment. As per recently updated European Society for Medical Oncology recommendations, first-line treatment with up to 4 cycles of platinum-etoposide combined with immune checkpoint inhibitor (ICIs)-targeting PD-L1, is now the standard of care. The purpose of the current analysis is to identify current patient profiles and treatment strategies in real life clinical practice, and report outcomes in Extensive Stage (ES)-SCLC. MethodsNon-interventional, retrospective, multicentre, comparative study was carried out to describe the outcome of ES-SCLC patients included in the Epidémiologie Stratégie Médico–Economique (ESME) data platform for advanced and metastatic lung cancer. Patients were selected from 34 health care facilities between January 2015 and December 2017, before the era of immunotherapy. Results1315 patients were identified, including 64% male and 78% under 70 year-old; 24% had at least 3 metastatic sites, mainly liver metastases (43%), bone metastases (36%), brain metastases (32%). 49% received only one line of systemic treatment; 30% and 21% received 2 and 3 lines or more, respectively. Carboplatin was more frequently used than cisplatin (71% and 29%, respectively). Prophylactic cranial irradiation was infrequent (4% of patients), but 16% of patients received thoracic radiation therapy, mainly after the completion of first-line chemotherapy (72% of patients); such strategies were more frequently applied in cisplatin/etoposide than carboplatin/etoposide patients (p = 0.006 and p = 0.015, respectively). After a median follow-up time of 21.8 (95% CI: 20.9–23.3) months, median real-world Progression-Free Survival (rw-PFS) was 6.2 (95% CI: 5.7; 6.9) and 6.1 (95% CI: 5.8; 6.3) months for cisplatin/etoposide and carboplatin/etoposide doublet regimens, respectively; 24-month rwPFS and Overall Survival were 3.2% (95% CI: 2.3; 4;2) and 22.2% (95% CI: 19.4; 25.1) in the whole population, respectively. ConclusionOur data provide with landmark reference findings on ES-SCLC before the immunotherapy era, and cover many aspects of the treatment strategy, while highlighting on the role of radiotherapy, subsequent lines of therapy, and the outcomes of patients. Generation of real-world data focusing on patients who received platinum-based chemotherapy combined with immune checkpoint inhibitors is under way.

Are Semiquantitative Methods Superior to Deauville Scoring in the Monitoring Therapy Response for Pediatric Hodgkin Lymphoma?

Tailoring treatment in patients with Hodgkin lymphoma (HL) is paramount to maximize outcomes while avoiding unnecessary toxicity. We aimed to compare the performance of SUVmax reduction (ΔSUVmax%) and the PET ratio (rPET) versus the Deauville score (DS) for assessing the chemotherapy response in pediatric HL patients undergoing 18F-FDG PET-CT. Fifty-two patients with biopsy-proven HL (aged 8-16 years) were enrolled at baseline, interim (after the second or third chemotherapy round) and post-therapy (on completion of first-line chemotherapy). Interim and post-therapy DS, ΔSUVmax% and rPET were compared as response predictors. Patients were classified as responders or non-responders based on a 24-month clinical follow-up. Interim DS showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of 100%, 80.4%, 100%, 40% and 82.7%, respectively, in predicting the therapy response. Post-therapy DS showed a sensitivity, specificity, PPV, NPV and accuracy of 66.7%, 97.8%, 95.7%, 80% and 94.2%, repsectively. Interim ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 82.6%, 97.4%, 38.5% and 82.7%, respectively, with a 56.3% cutoff. Post-therapy ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 84.8%, 97.5%, 41.7% and 84.6%, respectively, with a 76.8% cutoff. Compared to ΔSUVmax%, DS showed a significantly higher sensitivity, specificity (p < 0.05) and NPV (p < 0.01). The sensitivity, specificity, PPV, NPV and accuracy of rPET in predicting the therapy response at 24 months were 76.1%, 100%, 100%, 35.3% and 78.8%, respectively, with a cut-off of 1.31. DS and rPET showed comparable predictive performance (p > 0.58). In conclusion, DS is an easier method with better performance than ΔSUVmax% and rPET in predicting the chemotherapy response in pediatric HL patients.

The Impact of Chemosensitivity on the Outcome of Brain Metastases in Small-Cell Lung Cancer: A Retrospective Analysis.

Purpose: The purpose of this study was to investigate the prognostic differences between patients with small-cell lung cancer (SCLC) with different chemosensitivity to first-line chemotherapy who developed brain metastasis (BM) as the first site of progression. Methods: Patients with a BM after first-line treatment in the Tianjin Cancer Hospital were retrospectively analyzed. According to the time-free interval (TFI) between the completion of first-line chemotherapy and the onset of the BM, the patients were divided into the chemo-sensitive group (TFI ≥ 90 days, n = 145) and the chemo-resistant group (TFI < 90 days, n = 97). The survival time, which was calculated from the diagnosis of the BM, was analyzed after the onset of brain metastasis (BM-OS). Survival curves were plotted using the Kaplan–Meier method, and differences between groups were compared using the log-rank test. Results: In total, the median BM-OS was 8.4 months. The median BM-OS in the chemo-sensitive group was 8.8 months, and it was 8.0 months in the chemo-resistant group (p = 0.538). In patients without extracranial progression (n = 193), the median BM-OSes in the chemo-sensitive and chemo-resistant groups were 9.4 months and 9.7 months, respectively (p = 0.947). In patients with extracranial progression (n = 49), the median BM-OSes in the chemo-sensitive and chemo-resistant groups were 5.4 months and 4.2 months, respectively (p = 0.161). Conclusions: After the development of a BM as the first site of progression following chemotherapy in patients with SCLC, the prognosis of chemo-sensitive patients was not necessarily superior to chemo-resistant patients, especially in patients without extracranial progression.

Addition of Niraparib to Best Supportive Care as Maintenance Treatment in Patients with Advanced Urothelial Carcinoma Whose Disease Did Not Progress After First-line Platinum-based Chemotherapy: The Meet-URO12 Randomized Phase 2 Trial

BackgroundPlatinum-based chemotherapy (PBCT) is the standard first-line treatment for advanced urothelial carcinoma (UC). Potential cross-sensitivity can be hypothesized between platinum drugs and poly-ADP ribose-polymerase (PARP) inhibitors. ObjectiveTo compare maintenance treatment with the PARP inhibitor niraparib plus best supportive care (BSC) versus BSC alone in patients with advanced UC without disease progression after first-line PBCT. Design, setting, and participantsMeet-URO12 is a randomized, multicenter, open-label phase 2 trial. Patients with advanced UC, without disease progression after four to six cycles of PBCT, with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, were enrolled between August 2019 and March 2021. Randomization was stratified by ECOG performance status (0/1) and response to PBCT (objective response/stable disease). InterventionPatients were randomized (2:1) to experimental arm A (niraparib 300 or 200 mg daily according to body weight and baseline platelets, plus BSC) or control arm B (BSC alone). Outcome measurements and statistical analysisThe primary endpoint was progression-free survival (PFS). The analysis was performed on an intention-to-treat basis. The secondary endpoints reported in this primary analysis are progression-free rate at 6 mo and safety (adverse event rate). Results and limitationsFifty-eight patients were randomized (39 in arm A and 19 in arm B). The median age was 69 yr, ECOG performance status was 0 in 66% and 1 in 34%; and the best response with chemotherapy was objective response in 55% and stable disease in 45%. The median PFS was 2.1 mo in arm A and 2.4 mo in arm B (hazard ratio 0.92; 95% confidence interval 0.49–1.75, p = 0.81). The 6-mo progression-free rates were 28.2% and 26.3%, respectively. The most common adverse events with niraparib were anemia (50%, grade [G]3 11%), thrombocytopenia (37%, G3–4 16%), neutropenia (21%, G3 5%), fatigue (32%, G3 16%), constipation (32%, G3 3%), mucositis (13%, G3 3%), and nausea (13%, G3 3%). The main limitation of the study is the small sample size: in March 2021, approval of maintenance avelumab for the same setting rendered randomization of patients in the control arm to BSC alone unethical, and accrual was stopped prematurely. ConclusionsAddition of maintenance niraparib to BSC after first-line PBCT did not demonstrate a significant improvement in PFS in patients with UC. These results do not support the conduction of a phase 3 trial with single agent niraparib in this population. Patient summaryIn this trial, we tested the efficacy of niraparib as maintenance treatment in patients affected by advanced urothelial cancer after the completion of first-line chemotherapy. We could not demonstrate a significant improvement in progression-free survival with maintenance niraparib.

Prognostic Implication of Longitudinal Changes of Left Ventricular Global Strain After Chemotherapy in Cardiac Light Chain Amyloidosis.

AimCardiac involvement is the main prognostic determinant in AL amyloidosis. We sought to determine the prognostic significance of longitudinal change of left ventricular (LV) global longitudinal strain (GLS) in cardiac light chain (AL) amyloidosis patients undergoing chemotherapy.Methods and ResultWe retrospectively investigated 117 cardiac AL amyloidosis patients who underwent chemotherapy from 2005 to 2019. All patients underwent comprehensive 2D conventional transthoracic echocardiography at baseline and after completion of first-line chemotherapy. Speckle tracking analysis of images was performed offline. Absolute value of LV GLS was expressed as [LV GLS] and change of [LV GLS] after chemotherapy was expressed as Δ [LV GLS]. Clinical outcomes including cardiac response and all-cause mortality were analyzed.Baseline clinical and echocardiographic parameters were similar in patients with and without CR. Δ [LV GLS] significantly differed between the CR and non-CR groups (0.4 ± 2.8% in the CR group vs. −0.6 ± 2.5% in the non-CR group, P-value = 0.046). Δ [LV GLS] showed satisfactory predictive performance for all-cause mortality (cut-off value = 0.8%, AUC 0.643, 95% CI [0.537–0.748]). Adding Δ [LV GLS] to the Mayo stage + pre-chemotherapy [LV GLS] model showed incremental prognostic value (C-index: 0.637 vs. 0.708; Relative Integrated Discrimination Index 0.07, P-value = 0.003; Net Reclassification Improvement 0.54, P-value < 0.001). Δ [LV GLS] showed good correlation with cardiac response (AUC 0.820, 95% CI [0.737–0.904]).ConclusionIn cardiac amyloidosis patients who underwent chemotherapy, longitudinal change of [LV GLS] after chemotherapy showed significant association with overall survival as well as cardiac response.

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...

Implementation of a stepwise process for somatic testing in women with a new diagnosis of epithelial ovarian cancer

Objectives: Women with epithelial ovarian cancer (EOC) who have a germline mutation, somatic mutation or are found to have homologous recombination deficiency (HRD) have been shown to have an improved survival with use of a PARP inhibitor after completion of first-line chemotherapy. A quality improvement project aimed to develop a pathway for somatic/HRD testing in all patients with EOC. Methods: Standard quality improvement methodology was employed to complete a stakeholder analysis, process mapping, an Ishikawa diagram, a pro/con brainstorming session and a provider survey. Additionally, we benchmarked with another academic institution. Patient education material on genetic testing was developed. Plan-Do-Study-Act (PDSA) cycles were employed throughout the quality improvement process. All newly diagnosed patients with EOC who underwent surgery between January - June 2019 (preimplementation) and June-August 2020 (post-implementation) were identified. Data was abstracted from medical records to determine which patients were referred to genetics and which patients were provided with somatic testing recommendations. Results: Prior to implementation, 42.9% (30/70) patients who completed primary treatment of EOC had somatic testing ordered prior to completing primary adjuvant chemotherapy. Post-implementation, 63% (17/27) of patients had somatic testing recommended. Confining analysis to those patients who returned for a postoperative visit at the surgical institution, 77.8% (14/18) had somatic testing recommended. Germline testing referral and rates (countermeasure) did not change 88.6% (62/70) vs 85.3% (29/34) (pre versus post-implementation). Conclusions: Development of a structured process for somatic/HRD testing after surgery for EOC results improved rates of somatic testing discussion. A stepwise process ensures that these patients still receive the necessary counseling about germline testing prior to undergoing somatic/HRD testing. Women with epithelial ovarian cancer (EOC) who have a germline mutation, somatic mutation or are found to have homologous recombination deficiency (HRD) have been shown to have an improved survival with use of a PARP inhibitor after completion of first-line chemotherapy. A quality improvement project aimed to develop a pathway for somatic/HRD testing in all patients with EOC. Standard quality improvement methodology was employed to complete a stakeholder analysis, process mapping, an Ishikawa diagram, a pro/con brainstorming session and a provider survey. Additionally, we benchmarked with another academic institution. Patient education material on genetic testing was developed. Plan-Do-Study-Act (PDSA) cycles were employed throughout the quality improvement process. All newly diagnosed patients with EOC who underwent surgery between January - June 2019 (preimplementation) and June-August 2020 (post-implementation) were identified. Data was abstracted from medical records to determine which patients were referred to genetics and which patients were provided with somatic testing recommendations. Prior to implementation, 42.9% (30/70) patients who completed primary treatment of EOC had somatic testing ordered prior to completing primary adjuvant chemotherapy. Post-implementation, 63% (17/27) of patients had somatic testing recommended. Confining analysis to those patients who returned for a postoperative visit at the surgical institution, 77.8% (14/18) had somatic testing recommended. Germline testing referral and rates (countermeasure) did not change 88.6% (62/70) vs 85.3% (29/34) (pre versus post-implementation). Development of a structured process for somatic/HRD testing after surgery for EOC results improved rates of somatic testing discussion. A stepwise process ensures that these patients still receive the necessary counseling about germline testing prior to undergoing somatic/HRD testing.

Ovarian Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and is the country's fifth most common cause of cancer mortality in women. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. These NCCN Guidelines discuss cancers originating in the ovary, fallopian tube, or peritoneum, as these are all managed in a similar manner. Most of the recommendations are based on data from patients with the most common subtypes─high-grade serous and grade 2/3 endometrioid. The NCCN Guidelines also include recommendations specifically for patients with less common ovarian cancers, which in the guidelines include the following: carcinosarcoma, clear cell carcinoma, mucinous carcinoma, low-grade serous, grade 1 endometrioid, borderline epithelial, malignant sex cord-stromal, and malignant germ cell tumors. This manuscript focuses on certain aspects of primary treatment, including primary surgery, adjuvant therapy, and maintenance therapy options (including PARP inhibitors) after completion of first-line chemotherapy.

Abstract 2249: Checkpoint inhibitor therapy after dendritic cell vaccination elicits tumor response in mesothelioma patients

Abstract In mesothelioma most patients do not have functional T cells present in the tumor. Therefore, PD-1/PD-L1 checkpoint inhibitor (CI) therapy is likely to induce an anti-tumor response in only a small portion of patients. Activated autologous dendritic cells (DCs) that have been directed against mesothelioma tumor cells have been shown to reinvigorate T cell responses. This T cell response that is induced is prone to be blocked by the tumor using the PD-1/PD-L1 mechanism. Earlier, we published the results of three phase I/II trials in which patients were treated with DC immunotherapy as first line therapy of after completion of first line chemotherapy. 9 patients were subsequently treated with checkpoint inhibitor therapy in several trials and compassionate use programs. Six patients were treated with nivolumab, two with pembrolizumab and one patient was treated with combination treatment of nivolumab and ipilimumab. In all patients, the initial biopsy was stained for PD-L1 and TIM3, in five patients, repeat biopsy was done at time of progression. Radiological response was measured on CT scan using modified response evaluation criteria in solid tumors (RECIST). A radiological partial response was seen in three patients after PD-1 inhibition, stable disease was seen in five patients and one patients had progression of disease as best response on CI therapy, giving a disease control rate of 88%. No CTCAE grade 3-4 adverse events were seen. Updated adverse events, median PFS and OS will be presented at the meeting, as well as correlation of response with PD-L1 and TIM3 status. We conclude that CI treatment after DC immunotherapy is safe and feasible. In addition, after induction of a T cell response, disease control could be achieved in all but one treated patient on subsequent CI therapy. This report is a proof of concept that the induced T cell response from DC immune therapy may be blocked by PD-L1 upregulation from the tumor which in turn can be targeted by CI. Citation Format: Robin Cornelissen, Robert Belderbos, Joachim Aerts. Checkpoint inhibitor therapy after dendritic cell vaccination elicits tumor response in mesothelioma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2249.

Prognostic models for prediction of overall survival after first-line platinum-based chemotherapy for primary metastatic nasopharyngeal carcinoma.

e17501 Background: Platinum-based chemotherapy remains the main treatment strategy for patients with primary metastatic nasopharyngeal carcinoma (mNPC). However, survival outcomes are heterogeneous. The present study sought to develop clinical predictive models for overall survival (OS) in mNPC. Methods: Institutional database was queried for patients with mNPC who received first-line platinum-based chemotherapy between 2008 and 2015. Eligible patients (n = 460) were split into a training (2008-2013, n = 296) and an internal validation cohort (2014-2015, n = 164) according to the period of diagnosis. Potential prognostic factors for OS were evaluated using univariate and multivariate analyses. The performance of prognostic models was assessed by discrimination and calibration. The clinical usefulness of prognostic models was evaluated by decision curve analysis. Results: We established two nomogram-based prognostic models to predict OS probability, the first (baseline model) based on baseline factors, the second (composite model) incorporating posttreatment plasma Epstein-Barr virus DNA (EBV DNA) and objective response (OR) to first-line chemotherapy. The incorporation of posttreatment plasma EBV DNA and OR to the model improved the predictive accuracy. The C-index of composite model for predicting OS was 0.767 (P &lt; .001), which was statistically higher than the C-index values for baseline model (0.686). The results were confirmed in the internal validation cohort. Conclusions: We developed and validated two prognostic models that can be used before and after completion of first-line chemotherapy, respectively. The proposed models can be used for prognosis prediction and better selection of patient into clinical trials.

The Lower Peripheral Blood Lymphocyte to Monocyte Ratio Following Completion of First Line Chemotherapy Is a Risk Factor for Predicting Relapse in Patients with Diffuse Large B-Cell Lymphoma

Background and objective: During routine follow up, there is no specific predictor to ascertain relapse after standard first line chemotherapy in diffuse large cell lymphoma. Therefore, this study was designed to assess the prognostic significance of the ratio between absolute lymphocyte and monocyte counts (LMR) in the peripheral blood to verify relapse in diffuse large B cell lymphoma. Patients and methods: A total of 139 patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) were evaluated and treated with CHOP or R-CHOP between the years 2009 and 2016. Three months following completion of first line therapy, Lymphocyte/monocyte ratio (LMR) was calculated from the routine automated complete blood cell count (CBC) attained a plateau after the bone marrow recovery after first line chemotherapy. The absolute lymphocyte count/absolute monocyte count ratio (LMR) was calculated by dividing the ALC by the AMC. Results: ROC curve analysis of 139 patients established 2.8 as cutoff point of LMR for relapse with AUC of 0.97 (95% CI 0.93 - 0.99, P ≤ 0.001). Cox regression analysis was performed to identify factors predicting relapse. In univariate regression analysis, ALC (95% CI 0.003 - 0.03, p ≤ 0.001), AMC (95% CI 15.4 - 128.8, p ≤ 0.001), LMR (95% CI 0.001 - 0.01, p ≤ 0.001), and LDH (95% CI 0.1 - 0.5, p ≤ 0.001) following completion of therapy are significant factors for relapse. Other significant factors for relapse are Ann Arbor stage (95% CI 1.1 - 6.9, P = 0.03), extranodal sites (95% CI 1.2 - 6.1, P = 0.01), age (95% CI 1.3 - 6.5, P = 0.01) and treatment of CHOP protocol (95% CI 0.05 - 0.6, P = 0.007). In a multivariate analysis LMR following completion of therapy was predictive for relapse (95% CI 0.001 - 0.2, P = 0.005). ALC was also significant in multivariate analysis (95% CI 0.01 - 0.8, P = 0.03). LDH following completion of therapy (95% CI 0.2 - 14.9, P = 0.5), AMC following completion of therapy (95% CI 0.3 - 43.1, P = 0.3), age (95% CI 0.9 - 205.4, P = 0.06), extra-nodal sites (95% CI 0.04 - 9.8, P = 0.8), Ann Arbor stage (95% CI 0.3 - 28.7, P = 0.3), and Treatment of CHOP protocol (95% CI 0.01 - 2.4, P = 0.2) were not statistically significant. Conclusion: This study observed that LMR assessed after first line chemotherapy during routine follow up is an independent predictor of relapse and clinical outcome in DLBCL patients. LMR at follow up can be used a simple inexpensive biomarker to alert clinicians for relapse during follow up after standard first line chemotherapy in DLBCL patients.

The efficacy and safety of bevacizumab in addition to platinum-based chemotherapy for the first-line treatment of patients with advanced nonsquamous non-small-cell lung cancer: Final results of AVALANCHE, an observational cohort study.

The previous results of former clinical studies confirmed that first-line bevacizumab (BEV) in combination with chemotherapy improves clinical outcomes in patients with advanced non-squamous non-small cell lung cancer. The AVALANCHE study (ClinicalTrials.gov Identifier NCT03170284) was undertaken to assess the clinical outcomes of first-line BEV combined with standard platinum-based regimens in the Hungarian clinical practice. This observational study was conducted in 28 Hungarian sites, with patients enrolled between July 2008 and April 2011. Patients with untreated locally advanced, metastatic or recurrent lung adenocarcinoma received BEV (7.5 mg/kg, q3w) with any platinum-doublet for up to 6 cycles, and then non-progressors proceeded to receive BEV until disease progression or unacceptable toxicity. The primary endpoint was time-to-progression, and secondary endpoints included overall survival (OS), tumour control rate and safety. Patients were also analysed as two cohorts (non-progressors vs. progressors) based on whether or not they received BEV maintenance therapy following completion of first-line chemotherapy plus BEV. The study enrolled 283 patients (median age: 58.2 (18–78) years; males: 50.5%; stage: III/B: 18.4%, IV: 79.9%; adenocarcinoma/other: 95.8/4.2%; ECOG PS 0/1/2/≥3: 30.8/59.7/2.6/1.4%). Centrally located tumours were reported in 21.6%. Cisplatin/carboplatin-based regimens: 53.8/46.2%. A total of 43% of patients received BEV maintenance therapy. The median number of BEV cycles was 6. Median progression-free survival (PFS) was 7.2 months and OS was 15.2 months for the entire cohort. Longer PFS and OS were observed in patients who received BEV maintenance therapy [median OS, 26.2 vs. 10.2 months (P<0.001); median PFS, 9.2 vs. 5.8 months (P<0.001)]. Contrary to the results of previous OCS no significant difference was recorded in the different age groups or gender. Best tumour response: Complete remission/partial remission/stable disease/progressive disease/not reported were: 1.5/29.9/26.9/9.1/32.6% of all patients. In conclusion, clinical outcomes obtained in this real-life population were consistent with pivotal studies. BEV maintenance treatment was associated with a significantly longer PFS and OS.

Praktyka kliniczna oceny minimalnej choroby resztkowej u chorych na szpiczaka plazmocytowego w Polsce: badanie ankietowe Polskiego Konsorcjum Szpiczakowego

Studies exploring the significance of minimal residual disease (MRD) in plasma cell myeloma (PCM) have proven its prognostic value, regardless of the type of administered treatment. In order to assess the current practice for evaluating MRD in Poland, we conducted a survey on the methods for assessing MRD and on the MRD testing time points at Polish hematological centres. Seven out of 15 institutions surveyed use of the flow cytometry (FC) method for MRD assessment. The FC-MRD assessment is performed uniformly only in those patients achieving complete remission (CR). However, the specific indications and assessment time points differed at the tested centres including: testing MRD only after autologous hematopoietic stem cell transplantation (auto-HSCT), after auto-HSCT and consolidation, after completion of first line chemotherapy or after obtaining CR in any line of treatment. The study also showed considerable heterogeneity in the FC-MRD methodology, which affects test sensitivity (from 10–3 to 10–5). None of the surveyed centres uses molecular techniques for MRD assessment. In 8 of the 15 institutions, patients are monitored by imaging techniques. Our survey may thus be useful for developing guidelines and standardization of MRD assessment in PCM in Poland.

Is third-line chemotherapy routine practice in recurrent or metastatic gastric cancer?

e15558 Background: Patients (pts) with recurrent or metastatic gastric cancer eventually experience disease progression during or after completion of first-line chemotherapy. Second-line therapy is generally recommended in the current guidelines. Although third-line therapy is often performed in daily practice in some countries, there are few reports about the benefit of third-line therapy. Methods: A retrospective review was conducted on 683 pts who underwent at least first-line palliative chemotherapy for recurrent (n = 297) or primary metastatic (n = 386) gastric cancer. Clinicopathological characteristics and overall survival (OS) were analyzed according to the lines of chemotherapy as well as for all study pts. Results: One hundred and forty-nine pts (21.8%) underwent third- or further-line therapy. Third- or further-line therapy was more frequently performed in pts with young age ( &lt; 70) (p &lt; 0.0001), ECOG PS 0 or 1 (p &lt; 0.0001) at the initiation of first-line therapy, first-line combination regimen (p = 0.006), and palliative surgical resection before first-line therapy (p = 0.029). The median follow-up duration was 62 months (24-151 months) for the survivors. The median OS for pts after first- and third-line therapy was 10 and 6 months, respectively. The median OS of pts who received third-line therapy was significantly longer than that of pts who received second- or lesser-line therapy (18 vs. 8 months, p &lt; 0.0001). Multivariate analysis revealed that third- or further-line therapy was independently associated with favorable OS (hazard ratio = 0.56, p &lt; 0.0001) along with surgical resection (p &lt; 0.0001) and first-line combination regimen (p = 0.008), whereas signet ring cell histology (p = 0.002) and peritoneal metastasis (p = 0.027) were independent prognostic factors of poor OS. Conclusions: This study suggests that recurrent or metastatic gastric cancer pts may benefit from third-line chemotherapy, although careful selection is essential.

Abstract 2252: Correlation of baseline value of folate receptor-positive circulating tumor cells and efficacy of pemetrexed and dynamic monitoring study in non-small cell lung cancer patients receiving first-line platinum-based chemotherapy

Abstract Background: The efficacy of pemetrexed associates with the expression of folate enzymes, however, few serological marker is available to predict its efficacy. Moreover, dynamic monitoring of circulating tumor cell (CTC) count can predict the outcome of tumor therapy, the progress of tumor and the overall survival of the patient. By quantitative determination of folate receptor-positive CTCs, this study investigated the correlation of its baseline values to the efficacy of pemetrexed and performed a dynamic monitoring study in non-small cell lung cancer (NSCLC) patients who underwent first-line platinum-based chemotherapy. Methods: This study enrolled 70 NSCLC patients who received first-line platinum-based chemotherapy. The CTCs were quantified by negative enrichment using immunomagnetic beads in combination with folate receptor-directed polymerase chain reaction(PCR) that allows secondary amplification of tiny amounts of CTCs in peripheral blood, thereby enhancing the sensitivity of detection. In this study, the CTC levels were examined by collecting 3mL of anti-ENTA whole blood samples before the treatment and after every chemotherapy, and followed up until progressive disease (PD) or completion of first-line chemotherapy. Based on the changes in CTC levels, we evaluated the correlation of the changes in CTC levels and the progress of the disease as well as the correlation of the CTC levels and the therapeutic outcomes. Results: The CTC level of seventy patients was 13.68 CU/3mL. Of twenty-two patients who received pemetrexed disodium/platinum combined therapy (AP/AC), the patients harboring high levels of folate receptor showed greater efficacy than those with low expression levels (8.7&amp;lt;CTC level&amp;lt;16, n = 7; PFS: 448 vs.94days, P = 0.0199; ORR: 75% vs.11%). In the dynamic monitoring study, the CTC level (AUC = 0.8026,P = 0.0033), the CTC ratio (AUC = 0.8422,P = 0.0003), the rate of CTC changes (OR = 102.005,P = 0.0012) after the second chemotherapy and the CTC level (AUC = 0.9487,P&amp;lt;0.0001), the CTC ratio (AUC = 0.8889,P&amp;lt;0.0001), the changing rate of CTCs (OR = 51.662,P = 0.0031) after the fourth chemotherapy positively correlated to the disease progression. Conclusions: The patients with high expression of folate receptor-positive CTCs appear to have superior response to pemetrexed than those with low expression. Additionally, the changes of CTC count can be used as a dynamic monitoring indicator in the treatment process to evaluate tumor burden and therapeutic outcomes. Citation Format: Xiaoxia Chen, Caicun Zhou, Xuefei Li. Correlation of baseline value of folate receptor-positive circulating tumor cells and efficacy of pemetrexed and dynamic monitoring study in non-small cell lung cancer patients receiving first-line platinum-based chemotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2252.

Bevacizumab Continuation Versus Treatment Holidays After First-Line Chemotherapy With Bevacizumab in Patients With Metastatic Colorectal Cancer: A Health Economic Analysis of a Randomized Phase 3 Trial (SAKK 41/06)

BackgroundBevacizumab (BEV)-containing therapies are costly. We performed a health economic analysis of a randomized phase 3 study (SAKK 41/06) that compared BEV continuation as a single agent (BEV) with treatment holidays (no BEV) after completing 4 to 6 cycles of first-line chemotherapy plus BEV in metastatic colorectal cancer patients. Patients and MethodsCosts for first-line chemotherapy with BEV, BEV continuation therapy, hospitalizations (length of stay), control visits, diagnostic tests, and second-line and later rounds of chemotherapy were collected. Mean costs per patient per treatment arm and an incremental cost-effectiveness ratio were calculated. Probabilistic sensitivity analysis was performed to account for uncertainty in the input parameters. ResultsThe total incurred mean costs per patient were 126,631 Swiss francs (CHF) [95% confidence interval (CI), 116,521-136,740] for BEV versus CHF100,146 (95% CI, 92,811-107,481) for no BEV. The incremental cost effectiveness ratio was CHF108,991 per life-year gained (LYG; 95% CI from probabilistic sensitivity analysis, 62,890-248,515). Compared to a willingness-to-pay threshold of CHF100,000/LYG, there was 42% probability that BEV continuation was cost effective, which decreased to 20% at a threshold of CHF75,000/LYG. Economic equality was reached in only 0.07% of cases. ConclusionThe clinical conclusion that BEV continuation as a single agent after completion of first-line chemotherapy is of low therapeutic value is supported by this health economic analysis. Costs increase without significant clinical benefit in this setting.

PLATFORM: Planning treatment of oesophago-gastric (OG) cancer—A randomised maintenance therapy trial.

TPS187 Background: Outcomes for patients with advanced OG cancer remain poor, median overall survival for fit patients treated with platinum and fluoropyrimidine based chemotherapy is less than one year, with second line chemotherapy resulting in a modest (approximately 6 weeks) survival benefit for selected patients. Evidence from NSCLC trials suggests a survival benefit from maintenance treatment following first line chemotherapy. Emerging data also supports the use of immunotherapy in previously treated OG cancer. The PLATFORM study aims to evaluate maintenance therapy in patients with advanced OG cancer. Methods: This is a prospective, open label, multicentre, randomised phase II clinical trial which will recruit at multiple UK cancer centres. Eligible patients are those who have measurable stable disease or better following completion of first line chemotherapy (at least 6 cycles) for locally advanced unresectable or metastatic disease. First line chemotherapy regime should contain a platinum and 5-fluoropyridimine (with trastuzumab if HER2 +), doublet or triplet drug combinations are permitted. Maintenance strategies are split by HER 2 status. For HER2 negative patients these are: Arm A1: surveillance, Arm A2: capecitabine, Arm A3: MEDI 4736 (anti PDL1 inhibitor) and for HER2 positive patients; Arm B1: trastuzumab, Arm B2: in development. Target recruitment is six hundred and sixteen patients, 154 patients will be recruited to each arm, with an interim analysis following recruitment of 61 patients to each arm. An adaptive trial design enables ineffective treatments to be discontinued early, with the opportunity to add novel treatment arms as the trial progresses. Primary endpoint is progression free survival. Secondary endpoints are progression free rate at 3, 6 &amp; 12 months, overall survival, objective response rate by RECIST 1.1, toxicity and analysis of efficacy endpoints according to biomarker status for selected arms. Thirty two patients have been registered for the study with 3 patients randomised, recruitment is ongoing. Clinical trial information: EUDRACT: 2014-002169-30.

A case of Pneumocystis jiroveci pneumonia after bendamustine-based chemotherapy for refractory diffuse large B-cell lymphoma.

A case of Pneumocystis jiroveci pneumonia after bendamustine-based chemotherapy for refractory diffuse large B-cell lymphoma.

Treatment Patterns, Costs, and Survival among Medicare-Enrolled Elderly Patients Diagnosed with Advanced Stage Gastric Cancer: Analysis of a Linked Population-Based Cancer Registry and Administrative Claims Database.

PurposeTo assess real-world treatment patterns, health care utilization, costs, and survival among Medicare enrollees with locally advanced/unresectable or metastatic gastric cancer receiving standard first-line chemotherapy.Materials and MethodsThis was a retrospective analysis of the Surveillance, Epidemiology, and End Results-Medicare linked database (2000~2009). The inclusion criteria were as follows: (1) first diagnosed with locally advanced/unresectable or metastatic gastric cancer between July 1, 2000 and December 31, 2007 (first diagnosis defined the index date); (2) ≥65 years of age at index; (3) continuously enrolled in Medicare Part A and B from 6 months before index through the end of follow-up, defined by death or the database end date (December 31, 2009), whichever occurred first; and (4) received first-line treatment with fluoropyrimidine and/or a platinum chemo-therapy agent.ResultsIn total, 2,583 patients met the inclusion criteria. The mean age at index was 74.8±6.0 years. Over 90% of patients died during follow-up, with a median survival of 361 days for the overall post-index period and 167 days for the period after the completion of first-line chemotherapy. The mean total gastric cancer-related cost per patient over the entire post-index follow-up period was United States dollar (USD) 70,808±56,620. Following the completion of first-line chemotherapy, patients receiving further cancer-directed treatment had USD 25,216 additional disease-related costs versus patients receiving supportive care only (P<0.001).ConclusionsThe economic burden of advanced gastric cancer is substantial. Extrapolating based on published incidence estimates and staging distributions, the estimated total disease-related lifetime cost to Medicare for the roughly 22,200 patients expected to be diagnosed with this disease in 2014 approaches USD 300 millions.