3rd Line Treatment Research Articles

Eribulin Suppresses New Metastases in Patients With Metastatic Breast Cancer.

This study aimed to investigate the progression type of metastatic breast cancer (MBC) in patients undergoing eribulin chemotherapy. We retrospectively investigated the cases of 66 consecutive patients with MBC who underwent eribulin chemotherapy. A total of 15 patients (22.7%) received eribulin as a 3rd-line or later treatment, and 17 (25.8%) received eribulin as a 1st-line treatment. The overall response was complete response in 0 (0%), partial response in 15 (22.7%), stable disease in 27 (40.9%), and progressive disease in 24 (36.4%) patients. By the time of data cut-off, time to treatment failure (TTF) events had been observed in 60 patients (90.9%), among whom, 15 (25%) had disease progression due to NM, and 45 (75%) had disease progression due to PL. In the regimen before eribulin administration, among 49 patients, 24 (49.0%) had disease progression due to NM. Luminal-type patients and those with triple-negative breast cancer exhibited a similar tendency, i.e., the rate of NM was lower in the patients treated with eribulin. The rate of NM was lower in the patients treated with eribulin in the 1st-line setting than that in patients treated with eribulin as a later treatment. Eribulin has a potential antitumor mechanism to prevent new metastasis. Eribulin may be effective against both the epithelial-mesenchymal transition (EMT) process and new metastasis.

Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer - study protocol of the FORCE trial

BackgroundHypofractionated palliative radiotherapy for metastatic lung cancer patients is frequently used in order to ease pain, to increase bone stability, to treat local mass effects, or to prolong progression-free survival at critical sites. Recently introduced, immunotherapy for patients with non-squamous non-small cell lung carcinoma (NSCLC) has significantly improved outcome in this cohort. Preclinical and early clinical data suggest that the combination of photon radiation with programmed death-1 (PD-1) targeting immunotherapies may promote a strong and durable immune response against tumor manifestations both within and beyond radiation targets.Methods/designIn the present prospective, two-group, non-randomized, open-label phase II trial, 130 patients with stage IV non-squamous NSCLC in 2nd-line or 3rd-line treatment will be included. 65 patients with a clinical indication for palliative radiotherapy to non-cerebral/non-pulmonary metastatic sites will receive 240 mg nivolumab followed by palliative radiotherapy with 5 × 4 Gray (Gy) = 20 Gy photon radiation, which will be initiated within 72 h after first nivolumab administration (Group A). 65 patients without an indication for radiotherapy will only receive nivolumab (Group B). Nivolumab will be further administered every two weeks in both groups and will be continued until progression and loss of clinical benefit or until occurrence of limiting toxicities.The primary endpoint will be the objective response rate (ORR) according to response evaluation criteria in solid tumors (RECIST) 1.1. Secondary endpoints will be progression-free survival (PFS) according to RECIST 1.1, overall survival, descriptive subgroup analyses according to PD-L1 expression, toxicity and quality of life. Since response patterns following immunotherapies differ from those after conventional cytostatic agents, both objective response rate and progression-free survival will additionally be assessed according to immune-related RECIST (irRECIST) criteria.DiscussionThe FORCE study will prospectively investigate response rates, progression-free and overall survival (OS), and toxicity of nivolumab with and without hypofractionated palliative radiotherapy in a group of 130 patients with metastatic non-small cell lung cancer (non-squamous histology) in 2nd-line or 3rd-line treatment. This trial will contribute prospective data to the repeatedly published observation that the combination of hypofractionated photon radiotherapy and medical immunotherapy is not only safe but will also promote antitumoral immune responses.Trial registrationClinicaltrials.gov identifier: NCT03044626 (Date of initial registration: 05 January 2017).Eudra-CT Number: 2015–005741-31 (Date of initial registration: 18 December 2015).

P1.14-54 Previous Therapy Strategy Impact on Efficiency of Anlotinib Hydrochloride as 3rd Line Treatment: A Subgroup Analysis of ALTER0303 Trial

P1.14-54 Previous Therapy Strategy Impact on Efficiency of Anlotinib Hydrochloride as 3rd Line Treatment: A Subgroup Analysis of ALTER0303 Trial

735P - Second-line chemotherapy (SLC) in patients with advanced biliary tract and gallbladder cancers (ABGC) prolongs survival: A retrospective population-based cohort study

BackgroundLimited evidence is available regarding survival benefit of SLC in patients with ABGC. After failure of first-line treatment, currently no "standard" second-line therapy is available. There is a lack of randomized clinical trials and well-designed population-based study to address this important question in the management of ABGC. In this population-based cohort study we evaluated if SLC prolongs survival in patients with ABGC. MethodsPatients with biopsy proven ABGC who were diagnosed in the province of Saskatchewan during the period of 2006 to 2015 and received first-line chemotherapy were assessed. Based on the use of SLC, patients were divided into ‘Treatment’ group or ‘Control’. Cox proportional multivariate analyses were performed to determine survival benefit of SLC. Results136 eligible patients with median age of 66 (IQR, 55-73) and M:F of 1:1.34 were identified. Primary tumor sites were as followed: gallbladder 31%, intrahepatic cholangiocarcinoma 36%, bile duct 23%, and ampullary 10%. 68% patients had metastatic disease.37% patients received SLC and of those 42% received combination therapy. There were significant differences between the two groups with respect to age and baseline liver function. The median overall survival (mOS) of treatment group was 17 months (95%CI, 12.5-21.5) vs. 7 months (5.3-8.7) of control (p<0.0001). Patients who received combination SLC had mOS of 20 months (14.0-26.1) vs. 17 (13.5-20.5) with single agent chemotherapy (p=0.73). On progression 36% received 3rd or subsequent line treatment. On univariate analysis SLC HR 0.51 (0.35-0.73), bilirubin 0.52 (0.34-0.79), and neutrophil to lymphocyte ratio (NLR) 1.11 (1.07-1.16) significantly correlated with survival. Test for interaction between SLC and all the other variables were not significant. On multivariate analysis SLC HR 0.55 (0.36-0.83) and NLR 1.10 (1.05-1.15) were significantly correlated with survival. ConclusionsThis well-designed population based cohort study suggests a substantial survival benefit associated with SLC. Patients with ABGC who are potential candidate for chemotherapy should be offered active treatment or participation in the clinical trial. Legal entity responsible for the studyThe authors. FundingSaskatchewan Cancer Agency Research Grant. DisclosureAll authors have declared no conflicts of interest.

1065O - Interim evaluation of a targeted radiotherapeutic, CLR 131, in relapsed/refractory diffuse large B-cell lymphoma patients (R/R DLBCL)

BackgroundForty to fifty percent of newly diagnosed DLBCL patients will relapse and another 10% will be refractory to initial therapy. Despite the introduction of new therapies, outcomes for patients with R/R DLBCL remain poor with no improvement in progression free survival (PFS), overall survival (OS) or response rates (ORR). Patients receiving 1 additional line of treatment have an OS of ∼13 months post relapse and for those requiring 3rd line treatment or more, only 10% survive for 12 months. CLR 131 is a novel therapeutic being evaluated in R/R DLBCL. CLR 131 leverages a novel delivery mechanism that takes advantage of a metabolic shift in tumor cells to allow the targeted delivery of I-131 directly into tumour cells. MethodsA multi-center study is being conducted to evaluate the safety and efficacy of CLR 131 in patients with R/R DLBCL. An interim assessment was conducted to determine cohort expansion and continued enrollment of up to 40 additional patients. The criteria for expansion was a minimum 20% of patients experience clinical benefit (CBR) or better. Patients in this assessment received a single 25mCi/m2 30-minute infusion of the targeted radiotherapeutic CLR 131 on day 0. Patients were then followed until disease progression. The primary endpoint is CBR. Secondary endpoints included ORR, PFS and OS. ResultsSix R/R DLBCL patients having received an average of 3 prior lines of therapy received a single infusion of CLR 131. Overall 3/6 patients achieved CBR, 1 patient experienced a complete response (CR) with a total reduction in tumor volume of greater than 99% and continues to be a CR at nearly 8 months post dosing. One patient with cutaneous R/R DLBCL achieved a partial response (PR) with a 56% reduction in total tumor volume and 1 achieved stable disease. The average duration of response was ∼5 months and continues to be monitored. PFS and OS have not been reached at the time of submission. ConclusionsIn this interim evaluation of CLR 131 in R/R DLBCL patients, significant and durable responses were exhibited, including a 33% ORR, 15% CR and 50% CBR. Patients experienced durable responses (assessment continues). Larger, prospective trials are needed to elucidate optimal patient and dosing schedule of CLR 131 in these patients. Clinical trial identificationNCT02952508. Legal entity responsible for the studyCellectar Biosciences, Inc. FundingNational Institutes of Health, National Cancer Institute. DisclosureJ. Longcor: Full / Part-time employment: Cellectar Biosciences, Inc. K. Oliver: Full / Part-time employment: Cellectar Biosciences Inc. J. Friend: Full / Part-time employment, Formerly: Cellectar Biosciences Inc. All other authors have declared no conflicts of interest.

Association of gastric acid suppression with efficacy of immune checkpoint inhibitors (ICIs) in advanced cancer patients

Abstract Background Recent studies have shown that proton pump inhibitor (PPI) negatively impacts on the clinical benefit from ICIs. Gut microbiome modulated by PPI may contribute to decreased efficacy. It has been also reported that H2 blocker (H2B) or gastrectomy affected gut microbiome. We assessed in this study the association of GAS including PPI, H2B and gastrectomy with clinical outcome from ICI. Methods We retrospectively investigated advanced cancers pts treated with ICIs as the 1st- to the 3rd-line treatment at our institution between July 2014 and September 2018. GAS was defined as using PPI or H2B within 30 days before start of ICI, or having past history of gastrectomy. Response to ICIs was assessed by RECIST v1.1. Performance status (PS), body mass index, antibiotics, steroid, LDH level, albumin level, CPR and neutrophil-lymphocyte ratio (NLR) were compared between the GAS and non-GAS arms. Associations of nominal variables with the response were evaluated. Results Total of 115 pts (lung 69.9%, skin 11.3%, head and neck 7.8%, renal cell 6.9%, stomach 4.2%, and urothelium 2.5%) were evaluated. The types of ICIs were nivolumab of 72.2%, pembrolizumab of 22.6%, and atezolizumab of 5.2%. Sixty of 115 pts recieved GAS (PPI 83.3%, H2B 11.6%, and gastorectomy 5%) before start of ICI. Patients’ characteristics between the GAS and non-GAS arms was almost well balanced. However, pts with lower PS (>2) or high NLR were more frequently observed in the GAS arm (20% vs. 0%, 40% vs. 16%, respectively). The response rate (RR) was almost significantly lower in the GAS arm than the non-GAS arm (12% vs. 25%, P = 0.055). GAS did not remain statistically significant in a multivariate analysis (P = 0.091), while LDH was significant in both uni- and multivariate analyses. Conclusion Pts with GAS and pts without GAS have different patients’ background such as PS and NLR, and the RR in pts with GAS was numerically lower compared to that without GAS in advanced cancer treated with ICI.

BRCA mutation frequency and clinical features of ovarian cancer patients: A report from a Chinese study group.

Subjects with germline BRCA1/2 mutations (gBRCAm) have an increased risk of developing breast cancer and ovarian cancer. At present, knowledge of BRCA1/2 mutation frequency in Chinese patients with ovarian cancer is still insufficient, and the detailed clinical information of these patients is poorly understood. A total of 547 unselected ovarian cancer patients were enrolled, and their gBRCAm status was detected. Clinical characteristics including age, personal and family history, histopathologic diagnosis, carbohydrate antigen 125 (CA-125) level, ascites, Federation International of Gynecology and Obstetrics (FIGO) stage, residual lesions, platinum sensitivity, recurrence interval and survival information were collected. Accurate assessments of disease response were based on the RECIST standard or CA-125 level. In 547 patients with ovarian cancer, we detected 129 (23.6%) patients with pathogenic mutations, 84 patients with BRCA1 mutations (15.4%) and 45 patients with BRCA2 mutations (8.2%). Twenty-five novel mutations were identified, and the mutation of BRCA1, c.5470_5477del8, was the most common mutation in this study. BRCA1/2 mutations were significantly associated with age; personal and family history; FIGO stage; secondary recurrence interval; sensitivity to platinum in 1st, 2nd and 3rd line treatment; and response to doxorubicin liposomes. Patients with BRCA1/2 mutations showed significant advantages in 3- and 5-year survival rates but no advantage in long-term survival. BRCA1/2 mutation prevalence in Chinese ovarian cancer patients is higher than the international rate. We recommend BRCA1/2 testing for patients with family histories and personal histories of malignancy and genetic counseling for cancer in healthy people with high-risk family histories.

Efficacy and adverse reactions of apatinib in advanced gastric cancer

Objective To investigate the effects and adverse reactions of apatinib in advanced gastric cancer patients. Methods Two hundred and forty cases of advanced gastric cancer patients who had failed chemotherapy were collected from January 30, 2016 to November 1, 2017 in the First Hospital of Zibo City of Shandong Province and the Central Hospital of Zibo City of Shandong Province. All patients took oral apatinib mesylate, 850 mg/time, 1 time/d, and 28 d as 1 cycle of treatment, during which clinical efficacy, adverse reaction and progression free survival (PFS) and overall survival period (OS) were evaluated. Adopting Cox regression model to analyze risk factors of PFS and OS. Results Of all 240 patients, no patient reached complete response (CR) standard, 25 patients (10.4%) reached partial response (PR) standard, 113 patients (47.1%) reached stable disease (SD) standard, and 102 patients (42.5%) reached progressive disease (PD) standard. Objective response rate (ORR) and disease control rate (DCR) were 10.4% (25/240) and 57.5% (138/240) respectively. When apatinib was taken as a 2nd line treatment, ORR and DCR were 62.5% (5/8) and 75.0% (6/8) respectively; as 3rd line treatment, the result came to 13.9% (20/144) and 67.4% (97/144); as 4th line treatment, it was 0 and 52.4% (33/63); as 5th line treatment, it was 0 and 8.0% (2/25). Among the various adverse effects of apatinib, the most common ones observed were skin lesion (65.8%, 158/240), fatigue (57.9%, 139/240), gastrointestinal reaction (45.4%, 109/240), and hypertension (38.8%, 93/240). Cox multivariate analysis showed that the change of treatment time (HR=5.028, 95%CI: 1.130-15.771, P=0.005) and body mass index (HR=21.069, 95%CI: 4.521-127.116, P<0.001) were the independent risk factors of PFS. BMI change (HR=6.550, 95%CI: 1.080-38.455, P=0.039) was independent risk factor of OS. Conclusion For patients with advanced gastric cancer who failed with 2nd line and above chemotherapy, oral atatinib still obtain certain DCR and survival gain. Apatinib adverse reactions are various, involving a wide range of organ systems, however are generally controllable. Key words: Stomach neoplasms; Drug therapy; Apatinib

PS1254 CHARACTERISTICS AND OUTCOME OF PATIENTS WITH RELAPSED FOLLICULAR LYMPHOMA AFTER RETREATMENT WITH SECOND‐LINE RITUXIMAB‐CONTAINING CHEMOTHERAPY

Background:The prognosis of follicular lymphoma (FL) is considered favorable with rituximab‐containing first‐line chemotherapy (R‐CHEMO1). However, many patients will eventually require second‐line therapy, for which there is no current standard. Generally, patients receive a second course of rituximab‐containing chemotherapy (R‐CHEMO2) even though there are no prospective trials backing this approach.Aims:To characterize outcomes after R‐CHEMO2 of patients with relapsed biopsy‐proven grade 1–3A FL initially treated with R‐CHEMO1 ± maintenance rituximab (MR).Methods:We did a retrospective study of consecutive patients from 6 Canadian centres, excluding patients with transformed FL and those who received second‐line radiotherapy or chemotherapy alone.Results:129 patients with FL, 48% female, were included. Characteristics at diagnosis were a median age of 56 years (range 20–81), 84% stage III/IV, 35% high‐risk FLIPI. 33 (26%) were initially observed, and 5 (4%) initially received radiation. R‐CHEMO1 was R‐CVP in 95 (74%), R‐CHOP in 29 (23%), BR in 4 (3%), and FR in one patient. 73 (57%) received MR1.The median time from start of R‐CHEMO1 to start of R‐CHEMO2 was 36 months (range 2–145), with progression within 24 months of R‐CHEMO1 (POD24) in 49 (38%) patients. At start of R‐CHEMO2, the median year was 2011 (range 2004–2017), the median age was 60 (range 22–82). 80% had stage III/IV, 44% high‐risk FLIPI, 39% high LDH, 89% performance status 0–1. Second‐line regimens included 40 (31%) BR, 19 (15%) R‐CHOP, 19 (15%) R‐CVP, 17 (13%) FR, 17 (13%) platinum‐containing, and 17 (13%) other regimens. Overall response rate was 80% and complete response 37%. 40 (31%) patients received autologous stem cell transplantation (ASCT), 34 (26%) received MR2, and 5 received radiotherapy.With a median follow‐up in living patients of 5.2 years (range 1.1–13.3) after R‐CHEMO2, there have been 56 (43%) instances of progression (PROG2). 20 were biopsied (7 DLBCL, 13 FL) and 36 were not (2 aggressive and 34 indolent behavior). Median PFS2 was 6.4 years (95% CI 3.0–9.9) and 5‐year PFS2 was 54% (95% CI 53–55). 31 (24%) patients progressed within 6 months of R‐CHEMO2 or MR2. Age over 60 (HR 1.75, 95% CI 1.04–2.95, p = 0.036), ASCT (HR 0.26, 95% CI 0.13–0.53, p &lt; 0.001), and CR to R‐CHEMO2 (HR 0.22, 95% CI 0.11–0.44, p &lt; 0.001) were associated with PFS2.Median OS2 was not reached and 5‐year OS2 was 81% (95% CI 80–82). 27 patients died at the time of last follow up; 20 from lymphoma, and 7 from other causes. Elevated LDH (HR 3.22, 95% CI 1.42–7.28, p = 0.005), high FLIPI (HR 5.13, 95% CI 2.04–12.86, p &lt; 0.001), ASCT (HR 0.19, 95% CI 0.06–0.64, p = 0.007) and CR to R‐CHEMO2 (HR 0.31, 95% CI 0.11–0.89, p = 0.029) were associated with OS2.53/56 patients with progression after R‐CHEMO2 received 3rd line therapy, which was heterogeneous: 35 received R‐CHEMO3, 3 ASCT, 9 allogeneic SCT, and many patients received novel/experimental agents. The median time to 3rd line therapy was 1.5 years (range 0.13–8.1). 5‐year OS3 of 57% (95% CI 55–59) did not differ according to indolent vs. aggressive behavior (p = 0.306).Summary/Conclusion:Patients with relapsed FL treated with R‐CHEMO1 can be successfully treated with R‐CHEMO2 and achieve prolonged PFS2 and freedom from 3rd line treatment. Patients under the age of 60, those treated with ASCT, and those who achieve a CR have improved PFS2. Outcomes at progression after R‐CHEMO2 are less favorable, highlighting the need for other therapies in these patients. These data may provide benchmarking for clinical trial development and regulatory purposes.

PB1955 REAL LIFE DATA OF NILOTINIB IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA RESISTANT OR INTOLERANT TO IMATINIB

Background:Nilotinib is an effective treatment option for patient's refractory or intolerant to imatinib and can be given as 2nd or 3rd line treatment in Turkey.Aims:In this retrospective study, we aim to demonstrate the frequency of side effects in patients on Nilotinib.Methods:We analyzed 253 patients with chronic myeloid leukemia (CML) followed by Marmara University Hematology Department. 53 of these patients (%20.9) were on Nilotinib in a period of their treatment. Clinical characteristics of the patients are given in table 1.Results:Median duration of patients on imatinib before switching to 2ndline TKI were 19 months (1‐96). Reasons for changing therapy were primary imatinib resistance in 13 patients (%24.5), loss of response in 31 patients (%58.4), drug intolerance in 8 patients (%15.1). In one patient cause of treatment change could not be found.Nilotinib was used as 2nd line TKI in 37 of patients (%69.8) and was used after Dasatinib as 3rd line TKI in 16 of patients (%30.2). Median dasatinib treatment duration before switching to nilotinib was 14 months. Reasons for switching to nilotinib therapy were primary resistance in 3 patients (%18.7), loss of response in 4 patients (%25) and drug intolerance in 8 patients (%50).Nilotinib dosage were 800 mg, median duration of treatment on Nilotinib was 28 months (1‐120). 31 patients (%58.5) are still on Nilotinib. Reasons for discontinuation were primary Nilotinib resistance in 3 patients (%5.6), loss of response in 6 patients (%11.3) and drug intolerance in 8 patients (%15.1). Five patients were lost to follow up.Adverse events were seen on 21 patients (%39.6) and 9 of these (%17) were serious adverse events (SAE). SAE were ischemic cerebrovascular disease in 1 patient, myocardial infarct (MI) in 3 patients, acute pancreatitis in 2 patients, treatment‐resistant nausea‐vomiting in 1 patient, treatment‐resistant rash in 1 patient and grade IV thrombocytopenia in 1 patient. Treatment duration of Nilotinib in patients with MI were 24, 45 and 50 months. Cardiovascular risk factors were not observed in 2 of 3 patients who had MI; other patient had diabetes and hypertension. Treatment duration of Nilotinib in patients with pancreatitis were 1 and 25 months.Summary/Conclusion:In conclusion, Nilotinib is a highly effective treatment for patients who are refractory or intolerant to imatinib or dasatinib. Patients should be followed carefully in terms of side effects such as MI, arterial occlusive diseases and pancreatitis.image

PB2006 BRENTUXIMAB VEDOTIN PLUS BENDAMUSTINE IN RELAPSED OR REFRACTORY HODGKIN LYMPHOMA: A SINGLE CENTER EXPERIENCE

Background:Although the majority of patients with Classical Hodgkin lymphoma (HL) are cured with first‐line combined chemotherapeutic regimens, up to 15‐30% of patients have relapse or refractory disease. Brentixumab vedotin (BV) is an anti‐CD30 monoclonal antibody conjugated to the monomethyl auristatin E, which is a disrupting agent for microtubule function. BV monotherapy has 27% ‐35% CR rates in the second line setting prior to ASCT. Bendamustine is a fusion hybrid analogue and an alkylating agent containing purine analog; it can be used in relapsed non‐HL, was also evaluated in relapsed/refractory HL in the post‐ASCT setting; the overall response and CR rates were reported 53% and 33%. In a phase 1‐2 study, the complete response was achieved 72.6% and 92.5% with the combination of brentuximab vedotin plus bendamustine as the first salvage treatment for relapse refractory HL.Aims:In our study, we aimed to evaluate the response rates of brentuximab vedotin plus bendamustine combination experience in patients with relapsed or refractory HL.Methods:In this a single center retrospective study, between May 2018 and February 2019, we evaluated 17 patients for the treatment. The eligible patients were aged 18 years or older, had histologically confirmed relapsed or refractory Hodgkin's lymphoma. They received a dose of 1.8 mg/kg of brentuximab vedotin intravenously on day 1 of a 21 day cycle, plus one dose of 90 mg/m2 bendamustine intravenously on each of days 1 and 2 of a 21 day cycle Response evaluation was performed after at least 2 cycles of combination treatment.PET‐CT scans were done 4 to 6 weeks after the treatment for response assessment.Results:Seventeen patients were enrolled and the median age was 39 (19‐77). 61.6% of the patients were nodular sclerosing histologic subtype. At the time of diagnosis 71 % of the patients had advanced stage, 18% of the patients had bulky (&gt; 7 cm) disease. 60 % of the patients were primary refractory. The Brentixumab and bendamustin combination treatment was given as median 3rd line treatment (at least 2; maximum 7 lines). The objective response rate was 86.6% and complete response rate was 60 % as a result of the combination treatment. Refractory disease was observed 13.3% of the patients. Two patients experienced grade 3 pneumonia, two patients had neutropenia, one patient had anemia, one patient had severe motor neuropathy, two patients had diffuse hyperemic rash. No severe anaphylactic reaction was observed.Summary/Conclusion:Various salvage regimens are preferred for relapsed refractory (R/R) Hodgkin lymphoma patients, the CR rates varies between %20‐60. BV monotherapy was achieved 68% of total response rate and 35% of complete response rate before ASCT in R/R group. Considering the depth of response before ASCT and PET negativity as a predictive factor, the combination of BV and bendamustine as a salvage therapy for patients with R/R HL was achived high CR rates (72.6%) and overall response rates (92.5%). In general, the combination was well tolerated. In our study, 86.6 % overall response rates and 60% CR rate were achieved. In conclusion, the combination of BV and bendamustine therapy in relapsed/refractory HL is highly effective and has a manageable toxicity profile and it requires outpatient administration and reduce hospitalization. This combination can be evaluated in the patients who are not candidate for standard salvage treatment regimens due to comorbidity. It can be used as a bridge therapy especially proceeding ASCT associated with high response rates.

Clinical presentation, natural history and therapeutic approach in patients with solitary fibrous tumor: A retrospective analysis.

e22522 Background: Solitary fibrous tumor (SFT), a rare variant of soft tissue sarcoma (STS), is characterized by the presence of a NAB2-STAT6 fusion. Given the orphan character of SFT we performed a retrospective analysis. Methods: We retrospectively reviewed all patients (pts) with SFT treated in our institution between 12/1990 - 09/2017. Results: We identified 94 SFT pts (incl. hemangiopericytoma) with a med. follow-up for 4.7 yrs. Common anatomic sites were chest (33%), abdomen (21.3%), brain (12.8%) and extremities (9.6%). The symptomatology at diagnosis was variable. Only 6.4% presented with synchronous metastasis. Hypoglycemia (Doege-Potter syndrome) was seen in 2.1% of cases. A resection of the primary SFT was done in 86 pts (91.5%), their disease-free survival was 35.5 mo and 43% stayed SFT-free during follow-up. Local recurrence occurred in 26.7% of cases, associated with a med. overall survival (OS) of 45.1 mo. Metachronous metastasis was seen in 30.2% of pts, occurring after a med. follow-up of 36 mo. Med. OS after diagnosis of metastasis was 19.0 mo. Systemic therapy was given to 92.9% of pts with inoperable/metastatic disease. The most common 1st line therapy was doxorubicin single agent (57.7% of pts), achieving responses in 13.3% of pts. 2nd line therapies included ifosfamide and pazopanib (31.3% of pts each), 3rd line treatment was very heterogeneous. Conclusions: SFT is an orphan malignancy with a variable clinical course, low incidence of distant spread at first diagnosis but considerable risk of local failure and metachronous metastasis. Surgery is the only curative option at diagnosis, time of relapse and in case of resectable metastasis. Palliative systemic therapy is considered in pts with inoperable/metastatic disease but achieves low response rates. The natural course and survival outcomes of SFT cases treated with palliative intent tend to be better than in non-selected STS pts.

Efficacy and safety of nivolumab monotherapy as the late line for patients with advanced gastric cancer in the real-world.

e14074 Background: The ATTRACTION-2 study found that nivolumab showed a significant survival benefit for the patients with unresectable metastatic or locally advanced gastric cancer (AGC) following more than 2 regimens. Based on this trial, nivolumab was currently proved to be one of the most effective regimens for the patients with AGC as the 3rd-line treatment in Japan. We herein examined the clinical significance and validation of nivolumab as late line chemotherapy in patients with AGC. Methods: In October 2017 to December 2018, 26 patients received nivolumab monotherapy in our institute. We conducted a retrospective review of the data of 23 patients with AGC who received more than 2 cycles of nivolumab following the standard chemotherapy regimens including fluoropyrimidines, platinum derivatives and taxanes. Adverse events, tumor responses, and survival data were analyzed. Results: Only 2 patients enrolled here showed ECOG performance status (PS) 2 in the study. The time to treatment failure of them were shorter than those of the other patients with PS 0/1. Four patients quitted the continuation of nivolumab except for the progressive disease, due to non-hematological toxicities higher than grade 3 including myositis, hypothyroidism, dermatitis and liver dysfunction. The rate of hematological toxicities, which showed severe anemia of higher than grade 3 was 21.7%. The ORR and the DCR were 4.3% and 52.3% for the patients in this study. The survival data showed that the median PFS and the OS after nivolumab administration were 75 days and 274 days, respectively. Conclusions: Nivolumab monotherapy might be one of the best regimens for Japanese patients with AGC as the late line treatment following the standard chemotherapy.

A prospective, open label, multicenter, randomized phase II trial: Sequential therapy with bevacizumab, RAd001 (everolimus) and axitinib in metastatic renal cell carcinoma (mRCC) (BERAT study).

e16097 Background: Inhibitors of the vascular endothelial growth factor (VEGF), its receptor (Ri) or mammalian target of rapamycin (mTORi) are components of systemic treatment in metastatic renal cell carcinoma (mRCC) and are applied in sequence. We compared the efficacy of VEGFRi and mTORi in 2nd line after failure of bevacizumab/interferon in a phase II trial. Methods: Key inclusion criteria were: measurable mRCC (all histologies), ECOG 0-1, IMDC risk: good or intermediate, adequate organ function. Tumor status was assessed in week 11 and q12 wks., thereafter. Measures of Health-related quality of life (HR-QoL) utilized FKSI-10 and was assessed in week 4, 10 and q12 wks., thereafter. 1st line consisted of bevacizumab 10mg/kg q2wks. + interferon 9*106 IE 3x/week (BEV/IFN). Upon progression or intolerance, patients were re-screened and randomized between VEGFRi (axitinib 5 mg BID, dose-escalation permitted; sunitinib 50 mg OD, 4-2 regimen) and everolimus (EVE) treatment (10 mg OD). Cross-over occurred at time of progression or intolerance. Improvement of 2nd line PFS-rate at 6 mo. from 50% to 65% was the primary endpoint. Secondary endpoints were PFS, total PFS, ORR, OS, safety and HR-QoL. Results: Between November 2012 and June 2015 a total of 22 of 100 patients were included and at that time stopped for poor accrual. 10 pts. (46%) were randomized to receive 2nd line treatment with everolimus (n = 5) or VEGFRi (n = 5). At study entry (2/10) 20% had nephrectomy. ECOG 0 was recorded in 20% (EVE) and 60% (VEGFRi), respectively. Objective response rate (ORR) to 1st line BEV/IFN was 20%. In 2nd line treatment all patients experienced adverse events (AE). Grade ≥3 AEs occurred in 2/5 (40%) (EVE) and 4/5 (80%) (VEGFRi) pts., respectively. SAEs occurred in 3/5 (60%) in each arm. ORR was 1/5 (20%) for axitinib and 0/5 (0%) for EVE. PFS rate at 180 days was 20% in each arm. Median PFS was 3.7 (EVE) and 2.2 mo. (VEGFRi) HR 1.0 (95%CI 0.26-3.85; p = 0.997). OS was comparable between arms HR 1.12 (95%CI 0.27-4.61; P = 0.872). 7 pts. crossed over to 3rd line treatment. Conclusions: The small number of pts. randomized to EVE or VEGFRi is a major limitation of our trial, but may mirror the current change of treatment reality. However, no significant difference was detected for the PFS rate at 6 mo., indicating the limited activity of EVE or VEGFRi in 2nd line treatment. Clinical trial information: NCT01731158.

Management of Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Treated with Proteasome Inhibitor Based Therapy at First Relapse in Routine Clinical Practice in Germany

Background: Proteasome inhibitors (PI) represent an important therapeutic advance in the treatment of patients with relapsed/refractory multiple myeloma (RRMM). In 2017, three distinct PIs (bortezomib [BTZ], carfilzomib [CFZ] and ixazomib [IXA]) were available in Germany but real-world data describing their usage was scarce.Aim: To describe characteristics and treatment experience of PI-treated patients with RRMM in Germany.Methods: A national retrospective medical chart review included consecutive patients treated with at least one dose of PI-based regimen in participating hospitals/centers across Germany between January and June 2017. The following data were extracted until April 2018 or death of patient, whichever occurred first: patient demographics, disease characteristics and treatment history at diagnosis and at initiation of PI-based therapy. Physician assessed treatment response were also collected.Results: Physicians from 44 participating centers extracted 302 patient charts, including 219 patients in 2nd line (2L) and 83 in 3rd line treatment (3L), as shown in Figure 1. Results for 2L patients are described below (Table 1, Figure 2):BTZ-treated patients represented 42% of patients (n=92) with a PI-based therapy in 2L. BTZ was often combined with dexamethasone (dex) alone (77%). Median age was 74 years and 56.5% had an ECOG status ≥2 at 2L initiation. Most patients (86%) did not receive a prior transplant. Median treatment duration was 6 months among 40 patients who completed 2L; based on 38 narratives, 2L was ended as planned (47.4%). Where response was available (n=83), 25% of patients achieved a complete response/very good partial response [CR/VGPR]. Median time to next treatment (TTnT) was 7.5 months for 12 patients who moved to 3L. Patient profiles differed in terms of prior treatment exposure: 22% of patients had been treated with a BTZ-based therapy in both 1L and 2L and 62% switched therapies from 1L lenalidomide (len) to BTZ. None of the patients receiving len in 1L were transplanted. A CR/VGPR was achieved by 65% of prior BTZ-treated patients (13/20) and 30% of patients with prior len therapy (17/57).CFZ-treated patients: 48% (n=106) of patients received CFZ-based therapy in 2L. Of those, 56% (n=59) received CFZ in combination with len/dex (KRd) and 44% (n=47) with dex alone (Kd). Median age was 68 years, 60.4% had an ECOG status of 0-1 at 2L initiation and 49% had received a transplant. In 1L, 82% had received a BTZ-based regimen. Where response was mentioned (n=89), a CR/VGPR was reached in 53% of CFZ-treated patients. Median treatment duration was 6.5 months (24/106). Based on 21 narratives, the main reason for discontinuing CFZ in 2L was disease progression (47.6%). Median TTnT was 9.5 months for 10 patients who moved to 3L. The patient profiles by KRd or Kd combination were as follows: at KRd initiation, median age was 65 years, 10.2% of patients had an ECOG status ≥2 and 72.9% were transplanted. At Kd initiation, median age was 71 years, 76.6% of patients had an ECOG ≥2 and 19.1% were transplanted.IXA-treated patients (n=21) represented only 10% of PI-treated patients in 2L. Median age was 66 years, 71.4% had an ECOG status of 0-1 at 2L initiation, 33% were transplanted, and 72% had received a BTZ combination in 1L. Information on response was premature as it was only available for 13 patients with no CR reached (VGPR 77%). Median treatment duration was 4 months (n=9) and median TTnT was 10 months for 4 patients who moved into 3L.Limitation: The main limitation of the study was the sample size of IXA-treated patients due to open inclusion criteria to select patient charts. This analysis was not powered to compare between PIs. Hence, results are descriptive of the clinical experience with PI-based therapy to date and reflect current treatment practices in Germany in 2017.Conclusion: In Germany, distinct patient characteristics are observed in clinical practice by selected PI-based therapy. Patients treated with novel PI agents in 2L are generally younger and more transplanted than bortezomib-treated patients; these appear to be important considerations when tailoring therapy in RRMM. In addition, the choice between triplet or doublet therapy for CFZ-based combinations seems to reflect prior transplant status and patients' overall functional performance. Evidence suggests that use of novel PI agents such as CFZ can translate into deeper response in 2L. [Display omitted] DisclosuresSteinmetz:Amgen, Celgene, Novartis, Vifor: Research Funding; Amgen; BMS, Celgene, Hexal-Sandoz, Medice, Novartis; Janssen-Cilag; Pharmacosmos; Pfizer, Vifor; Ariad: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion, Amgen, Bayer, Celgene, Janssen-Cilag, Novartis: Other: Travel grants. Singh:Amgen: Employment, Equity Ownership. Lebioda:Amgen: Employment, Equity Ownership. Mantonnier:Kantar Health: Employment, Other: Received funding to conduct this research. Fink:Kantar Health: Employment, Other: Received funding to conduct this research. Rieth:Amgen: Employment, Equity Ownership. Suzan:Amgen: Employment, Equity Ownership. Gonzalez-McQuire:Amgen: Employment, Equity Ownership.

Subgroup analysis of histology in ALTER0303: Anlotinib hydrochloride as 3rd line and further line treatment in refractory advanced NSCLC patients (pts).

9080Background: In the ALTER0303 trial (NCT02388919), anlotinib hydrochloride was used as subsequence therapy for adult IIIB/IV NSCLC pts who progressed after at least 2 lines of prior systemic the...

Efficiency of anlotinib hydrochloride as 3rd line treatment in patients (pts) from a randomized, double-blind, placebo-controlled phase III trial, an exploratory subgroup analysis of ALTER0303 trial for the previous therapy strategy effect.

e21182Background: ALTER 0303 trial (NCT02388919) has demonstrated that anlotinib could significantly prolonged OS (primary point) and PFS in refractory advanced NSCLC pts as 3rd line treatment. Met...

Liquid biopsy to predict benefit from rechallenge with cetuximab (cet) + irinotecan (iri) in RAS/BRAF wild-type metastatic colorectal cancer patients (pts) with acquired resistance to first-line cet+iri: Final results and translational analyses of the CRICKET study by GONO.

12007Background: CRICKET (NCT02296203) was designed to investigate the activity of the rechallenge with cet and iri as 3rd-line treatment in RAS/BRAF wild-type mCRC pts with acquired resistance to ...

PCN90 - Treatment Patterns and Costs Associated with Diffuse Large B-Cell Lymphoma—A Retrospective Analysis of Claims

To assess treatment patterns and healthcare costs amongst patients diagnosed with diffuse large B-cell lymphoma (DLBCL), particularly during latter stages of therapy. This was a retrospective analysis of the Truven MarketScan® databases. Study eligibility criteria: 1) diagnosis of DLBCL, 2) ≥ 1 claim for DLBCL treatment in accordance with National Comprehensive Cancer Network guidelines, 3) 12+ months of pre-DLBCL continuous enrollment, 4) absence of other primary or secondary cancers in the 12-month pre-period (excluding lymphomas), 5) absence of DLBCL treatments in the 12-month pre-period, and 6) 18+ years of age at diagnosis. Outcomes included the frequency of specific regimens by line of therapy (LOT), and total healthcare costs associated with each regimen. Chemotherapy regimen analyses were conducted from the point of treatment initiation until the discontinuation of all agents, while autologous and allogenic stem-cell transplantations (SCT) were assessed for 30 days following the procedure. A total of 1,625 patients qualified for the study with 81.9% receiving 1 LOT, 14.3% receiving 2 LOTs, and 3.8% with ≥ 3 LOTs. The most common 1st line treatment was rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 66.5%), while the most common 2nd and 3rd line treatments (n=294) included SCT (2nd LOT (16.0%) and 3rd LOT (27.9%)). Mean healthcare expenditure during 1st LOT was $82,693 over a 90.0±50.6-day course; while 2nd LOT costs for only the SCT-related services were $164,460, with non-SCT treatment costs of $58,878 over 65.4±59.4 days. Similarly, 3rd LOT costs for only the SCT-related services were $127,295, with non-SCT treatment costs of $58,311 over 69.1±58.4 days. Costs of subsequent treatments are significantly greater among those who undergo both chemotherapy and SCT ($223,338 and $185,606 for 2nd and 3rd LOT, respectively). Such costs are likely underestimated when considering the downstream costs that are incurred after completion of treatment.

Third-line therapy in recurrent glioblastoma: is it another chance for bevacizumab?

Standard glioblastoma therapy is long-lasting. Among second-line therapy, choices could be bevacizumab and nitrosoureas depending on National Agencies approval. There is no consensus on 3rd line therapy or clinical trials specifically designed for this setting. We reviewed our institutional database on all consecutive patients who received 3rd line therapy for glioblastoma. Data on 168 out of 1337 (12.6%) glioblastoma patients who underwent 3rd line therapy treatment were collected. Third line treatments were bevacizumab or chemotherapy (nitrosourea, temozolomide or carboplatin plus etoposide). Median progression free survival was 2.9months and median survival time was 6.6 months from the start of 3rd line therapy. Bevacizumab significantly improved progression-free survival (4.7 vs. 2.6months, p = .020) and survival from 3rd line start (8.0 vs. 6.0months, p = .014) in respect to chemotherapy. Toxicity of grade ≥ 3 occurred in 13.7% of patients. In multivariate analysis, survival in 3rd line treatment depends on MGMT methylation (p = .006) and treatment with Bevacizumab (p = .011). Third line therapy in selected glioblastoma patients may be feasible and well tolerated. Bevacizumab improved outcome in 3rd line in respect to chemotherapy.