2nd Line Chemotherapy Research Articles

Impact of cetuximab sequence on progress-free survival (PFS) and overall survival (OS) in patients with RAS wild-type metastatic colorectal cancer (mCRC): A real-world study.

e16042 Background: Cetuximab provides a clear clinical benefit in the treatment in patients with RAS wild-type mCRC irrespective of treatment line, but the best sequence is still under investigation. Methods: Patients with RAS wild-type mCRC (2011-2019) who received cetuximab therapy were retrospectively analyzed. They were stratified based on the cetuximab treatment sequence, into the 1st, 2nd, 3rd or later-lines groups. The primary objective was to investigate the impact on Cetuximab sequence (2nd vs. 3rd and later-line) in PFS and OS. As for patients received the 3rd or later-line cetuximab with irinotecan therapy after refractory to the prior 1st and 2nd-line combined chemotherapy with fluoropyrimidine, oxaliplatin, and irinotecan, they will get another PFS of 2nd-line chemotherapy (PFSchemo) besides the PFS of 3rd or later-line cetuximab compared with the cetuximab 2nd-line used patients. We combined the PFSchemo to the PFS of 3rd or later-line cetuximab, then compared with PFS of 2nd -line cetuximab to evaluate the primary objective in PFS. As for the OS of primary objective, we calculated it from start of the 2nd-line of treatment. The secondary objective was to compare the efficacy of cetuximab sequence (1st vs. 2nd and later-lines) in OS calculated from start of the 1st-line of treatment. Results: In total, 193 patients were included: 106 in the 1st, 41 in the 2nd, and 46 in the 3rd-line groups. No difference was observed in baseline characteristics as sex,age,site of primary tumour,number of metastatic sites in the three groups. The median PFS of the 2nd-line and 3rd or later-line groups were 7.1 (95% CI 6.39-7.80) and 13.87 months(95% CI 11.44-16.29) respectively. PFS of the 3rd or later-line group was significantly longer than that of the 2nd-line group (hazard ratio[HR], 0.552; 95% CI, 0.349 to 0.871; P = 0.01). Median OS was 17.8 months (95% CI 13.5-22.1) in the 2nd-line and 27.4 months (95% CI 20.69-34.16) in the 3rd or later-line group (HR, 0.597; 95% CI 0.341 to 1.043; P = 0.07) from start of 2nd-line therapy. The median OS was 28.17 months (95% CI 22.11-34.22) in the 1st-line group and 33.10 months (95% CI 26.88-39.31) in the 2nd and later-lines group (HR, 0.724; 95% CI 0.507 to 1.304; P = 0.075) calculated from the 1st-line of therapy. Conclusions: In a real-world cohort we found that later-line especially 3rd or later-line therapy of cetuximab, may be more benefit for patients with RAS wild type mCRC, as 3rd or later-line use of cetuximab give one more line therapy chance.

Outcome of FOLFOX based chemotherapy in advanced pancreatobiliary cancers presenting with hyperbilirubinemia.

e16605 Background: Treatment of pancreatobiliary cancer patients with severe liver dysfunction including hyperbilirubinemia secondary to liver metastasis or biliary obstruction is challenging. A significant number of patients at presentation are in advanced/ locally advanced stage thus severely limiting chemotherapy options. FOLFOX (5 FU, Leucovorin, Oxaliplatin) represents a feasible option considering the pharmacokinetics. Clinical data on the dosage and tolerability of chemotherapy is limited and no recommendations are available to treat such patients in upfront setting with persistent hyperbilirubinemia. This observational study was done to find out safety and efficacy of FOLFOX based chemotherapy in these patients. Methods: Patients with advanced pancreatobiliary cancers with hyperbilirubinemia were treated with mFOLFOX6 based chemotherapy. Patients were treated till progression or 6 months or death (whichever occurred ealy) and assessed for toxicity and survival. Results: Only 13 out of 40 patients were able to complete all 12 cycle of chemotherapy. 12 patients were able to receive 2nd line chemotherapy of physician choice and 2 patients were able to received 3rd line chemotherapy. Total bilirubin of patients at start of chemotherapy ranged from 3 to 39.4 mg/dl with a mean value of 9.17±6.67 mg/dl and a median value of 7.5 mg/dl. Median progression free survival (PFS) of mFOLFOX6 was 5.97 months whereas median overall survival (OS) was 8.2 months. 6 patients were able to receive only one cycle of chemotherapy. 2 patients were able to receive only 2 cycles of chemotherapy. 26 patients completed 6 cycles of chemotherapy. Objective response rate was 45% after 6 cycles of chemotherapy. Of these 26 patients response assessment revealed progressive disease in 7 patients. 2 patient had complete metabolic response of which one of them had locally advanced disease. On laparotomy of this patient there were an extensive peritoneal disease curative surgery was not feasible. One patient successfully underwent Whipple’s procedure after 6 cycles of chemotherapy followed by adjuvant radiotherapy. Conclusions: FOLFOX based chemotherapy is a feasible option and a hope for patients of advanced pancreatobiliary cancers presenting with hyperbilirubinemia with a tolerable toxicity profile and providing comparable PFS and OS to other chemotherapy drugs/ regimens used in non hyperbilirubinemic patients.

Abstract A03: Association of Fusobacterium nucleatum (F. nucleatum) with progression-free survival (PFS) and overall survival (OS) with 2nd-line FOLFIRI +/- regorafenib in metastatic colorectal cancer (mCRC)

Abstract Background: F. nucleatum is an oral anaerobe aberrantly found in up to 43% of CRCs. F. nucleatum presence is associated with additional known prognostic variables, including BRAF mutation and immune infiltration. In nonmetastatic CRC, F. nucleatum is associated with post-chemotherapy recurrence and inferior cancer-specific survival. However, the prognostic value of F. nucleatum in mCRC is not well described. We evaluated the association between F. nucleatum, integrated with other significant prognostic clinicopathologic factors, in a prospective clinical trial cohort of mCRC. Methods: LCCC1029 was a 2:1 randomized phase II trial of 2nd-line chemotherapy with 5-fluorouracil/irinotecan plus either regorafenib or placebo in mCRC. DNA and RNA were extracted from FFPE archival tumor samples, and quantitative PCR to measure F. nucleatum levels was successfully performed on 73 of those samples. We compared PFS and OS using Kaplan-Meier method and log-rank tests, and univariate and multivariate hazard ratios (HR) were estimated using Cox proportional hazards method. Results: Among the 73 mCRC patients with F. nucleatum quantitated, 20 (27%) had a high level and 53 (73%) had undetectable or low levels of F. nucleatum. On univariate analysis, F. nucleatum high level was not associated with PFS (HR 0.78, 95% CI 0.46-1.33; log-rank p=0.36) or OS (HR 0.83, 95% CI 0.46-1.51; log-rank p=0.54). However, the F. nucleatum positive subgroup trended toward higher rates of BRAF mutation (12%, vs 2% in F. nucleatum low/negative), KRAS/NRAS mutation (47% vs 27%), and MSI-High (12% vs 5%). We thus performed multivariate analyses of PFS and OS including F. nucleatum high level, BRAF mutation, KRAS/NRAS mutation, MSI, prior antiangiogenic therapy, and age on the subgroup of 58 patients who had results from all platforms. On multivariate analysis, high F. nucleatum expression trended toward association with improved PFS, with HR 0.57 (0.30-1.10, p=0.095). BRAF mutation, prior antiangiogenic therapy, and F. nucleatum were significantly associated with improved OS, with high F. nucleatum expression having adjusted HR 0.48 (0.23-0.99, p=0.048). Conclusions: Expression of F. nucleatum in the tumor of patients with mCRC was significantly associated with improved OS in mCRC. While results need to be validated, these findings suggest that F. nucleatum is associated with prognosis in a context-dependent fashion and may confer differential prognosis in nonmetastatic versus metastatic CRC patients. Citation Format: Michael S. Lee, Temitope O. Keku, Amber McCoy, Sara R. Selitsky, Joel Parker, Todd Auman, Kelli Hammond, Sushant A. Patil, Ganiraju Manyam, Scott Kopetz, Hanna K. Sanoff, Federico Innocenti. Association of Fusobacterium nucleatum (F. nucleatum) with progression-free survival (PFS) and overall survival (OS) with 2nd-line FOLFIRI +/- regorafenib in metastatic colorectal cancer (mCRC) [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A03.

Abstract GS3-02: Durvalumab compared to maintenance chemotherapy in patients with metastatic breast cancer: Results from phase II randomized trial SAFIR02-IMMUNO

Abstract Background : While treatment with anti-PDL1 improves outcome in combination with chemotherapy in patients with metastatic triple negative breast cancer, its efficacy is not explored yet in the context of maintenance therapy after chemotherapy, in a population of Her2-negative metastatic breast cancer. Methods : In SAFIR02 trial (NCT : 02299999), patients are selected to present a Her2-negative metastatic breast cancer eligible to 1st or 2nd line chemotherapy. All patients underwent a biopsy of metastatic disease, followed by targeted sequencing and Oncoscan when >30% cancer cells are present on HES slides. After 6 to 8 cycles of induction chemotherapy, patients who present an actionable genomic alteration are randomized between targeted therapies and continuation of maintenance chemotherapy, and patients without actionable alterations are randomized between durvalumab (dose, schedule) for 2 years and maintenance chemotherapy. As a substudy of the SAFIR02-breast trial, the SAFIR02-IMMUNO trial has its primary endpoint, the PFS, hierarchized as the primary end-point of the core of the study. The plan was to include 190 patients in order to have 80% power using a two-sided logrank test at the 5 % level of significance to detect an improvement from 3 months to 4.76 months corresponding to an HR of 0.63. Results : 191 patients have been randomized between durvalumab and maintenance chemotherapy (190 women) until now, 45.5% TNBC and 53.4% RH+. The median age was 55 years. . 91.6% (175/191) patients were randomized on their first line of chemotherapy in metastatic setting. Median number of metastatic sites at the beginning of the chemotherapy line was 2. PDL1 staining was performed on 89 available tumor FFPE blocks using SP142 antibody. 30% (n=27/89) patients presented a PDL1 positive tumor. PFS and OS will be presented at the conference.Conclusion : This is the first randomized trial comparing aPDL1 inhibitor to chemotherapy in the maintenance setting and to address the question of the efficacy of aPDL1i in HR+/Her2- and triple negative breast cancers. Citation Format: Florence Dalenc, Ingrid Garberis, Thomas Filleron, Amélie Lusque, Thomas Bachelot, Monica Arnedos, Mario Campone, Marie-Paule Sablin, Hervé Bonnefoi, Marta Jimenez, Jacquet Alexandra, Fabrice Andre. Durvalumab compared to maintenance chemotherapy in patients with metastatic breast cancer: Results from phase II randomized trial SAFIR02-IMMUNO [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS3-02.

The treatment strategy of the second-line chemotherapy for metastatic colorectal cancer (mCRC) patients (pts) with early progression in the first-line chemotherapy with bevacizumab (BEV), BEV beyond progression (BBP), or non-BBP.

113 Background: BBP has been recognized as one of the standard 2nd-line treatment strategy for pts with mCRC based on the ML18147 trial. However, this trial excluded pts with disease progression < 3 months in the 1st-line BEV-containing chemotherapy. Methods: The subjects were mCRC pts who received the 2nd-line chemotherapy after experiencing disease progression < 100 days in the 1st-line BEV-containing chemotherapy between Apr 2010 and Dec 2016. This multi-institutional retrospective study compared the efficacy and safety between the 2nd-line chemotherapy with BEV (BBP) and without BEV (non-BBP), adjusting ECOG PS, WBC, ALP, number of metastatic sites, RAS status, and sidedness using Cox proportional hazard model. Results: 61 pts were evaluated. Patients' backgrounds were numerically different between BBP (n = 36) and non-BBP (n = 25), such as PS (0-1/2≤/unknown: 89/8/3 and 56/40/4%) and RASstatus (wild/mutant/unknown: 28/56/16 and 76/16/8%). There were no significant differences in age (median: 59 and 57), sex (male/female: 53/47 and 32/68%), tumor location (right/left: 44/56 and 40/60%), disease status (stage IV/recurrence: 67/33 and 84/16%), number of metastatic sites (1/2≤: 33/67 and 20/80%), the 1st-line regimens (oxaliplatin-based/irinotecan-based: 83/17 and 96/4%) between two arms. The 2nd-line chemotherapy regimens with EGFR antibody-containing/cytotoxic alone were 64/36% in non-BBP, respectively. The response rates were 5.9 and 8.7% in BBP and non-BBP. Median PFS were 3.7 and 2.8 months (HR 0.83, 95%CI 0.49-1.41, p = 0.486; adjusted HR 0.97, 95%CI 0.48-1.96, p = 0.932), respectively. The proportions of pts who received subsequent chemotherapy were 58 and 32% (p = 0.068). Median OS were 7.6 and 5.4 months (HR 0.70, 95%CI 0.41-1.19, p = 0.193; adjusted HR 0.65, 95%CI 0.34-1.25, p = 0.195). Common grade 3-4 adverse events (AEs) were neutropenia (11/24%) and anemia (3/16%), and other AEs were similar between two arms. Conclusions: The 2nd-line chemotherapy for pts with early progression in the 1st-line BEV-containing chemotherapy showed poor outcomes regardless of strategy.

Survival Outcomes After High-dose Chemotherapy and Stem Cell Transplantation in the Salvage Setting for Relapsed or Refractory Germ Cell Cancers.

High-dose chemotherapy (HDCT) and stem cell transplantation (SCT) have been established as the standard of care in patients with relapsed germ cell tumours (GCTs). We evaluated the safety, efficacy and tolerability of HDCT/ SCT in patients with relapsed GCTs. Twenty-eight patients with relapsed GCTs, treated with HDCT, were included in this study. The conditioning regime was carboplatin, etoposide, cyclophosphamide and paclitaxel. Clinical, radiological imaging and tumour markers determined treatment outcomes. Median age was 35 years (range=21-57 years) with 26 males and 2 females. Median time to first relapse was 6 months. Median time to progression after 2nd line chemotherapy was 17.3 months. Fourteen patients hadMedian survival was 62 months and 16 patients (57%) are in clinical follow-up with surveillance. In relapsed GCT patients, median survival may exceed 5 years post-HDCT and SCT.

Abstract C057: A phase I study to access the safety and efficacy of valecobulin (CKD-516), oral vascular disruption agent, in combination with irinotecan in patients with previously treated metastatic colorectal cancer

Abstract Background: Tumor neovascularization is a critical step for tumor growth and results in structurally and functionally abnormal tumor blood vessels. Vascular disrupting agents (VDAs) destroy established tumor vessels, subsequently causing tumor ischemia and necrosis. Valecobulin is an orally available VDA that acts as an inhibitor of tubulin polymerization. Thus valecobulin affects the central regions that are often resistant to conventional chemotherapy agents. Valecobulin combined with irinotecan showed significantly improved anti-cancer activity in colorectal cancer (CRC) bearing mouse models. On the basis of this background, we conducted a phase I dose-finding study of valecobulin in combination with biweekly irinotecan in CRC patient who had failed standard therapies including irinotecan basis regimen. Methods: Patients with metastatic CRC refractory to previous chemotherapy including one irinotecan containing regimen were enrolled in dose escalation cohort (Part A, traditional 3+3 design) and expansion cohort (Part B). The primary objective was to determine the recommended dose of expansion cohort in Part A, and to evaluate the antitumor activity and safety in Part B. All patient received valecobulin 5, 7, 9, or 11 mg/m2 PO on Day 1-5 and Day 8-12 (5 days of treatment followed by 2 days of rest) in combination with irinotecan 120 (Level 1-4) or 150 mg/m2 IV (Level 5) on Day 1 (14 days treatment cycle). Adverse events (AEs) and antitumor activity were evaluated using CTCAE V4.03 and RECIST V 1.1, each other. Results: A total 16 patients were enrolled to Part A, and 23 patients to Part B. Of 39 patients(≥19 years), 26(66.8%) were male, median age was 59 years(30-74). Past treatment history showed that most patients have already received 2nd (n=10; 25.6%), 3rd (n=12; 30.8%) or 4th line (n=13; 33.3%) chemotherapy. There was no dose limited toxicity until Level 5 and valecobulin 11 mg/m2 and irinotecan 120 mg/m2 (Level 4) was determined to the recommended dose of Part B according to reduction trend in whole treatment period. Among total 39 patients, the median progression-free survival was 126 days (95% CI: 83-175) and the overall survival was 361 days (95% CI: 240-526). PR was observed in 1 patient (2.9%) and SD was 26 (76.5%) among evaluable 34 patients. Common grade 3/4 AEs (>10%) regardless of cause included neutrophil decrease 51.3%, diarrhea 30.7% and vomiting 15.4%. The major cardiovascular events which were other VDAs’ common toxicity, were not observed. There were no treatment-related deaths. Conclusions Valecobulin in combination with irinotecan demonstrated a manageable safety profile and preliminary antitumor activity in chemotherapy refractory metastatic colorectal cancer. Citation Format: Tae Won Kim, Jeong Eun Kim, Hyeong-Seok Lim, Young Suk Park, Won Ki Kang, Sang Joon Shin, Joong Bae Ahn, Sae-Won Han, Tae-You Kim. A phase I study to access the safety and efficacy of valecobulin (CKD-516), oral vascular disruption agent, in combination with irinotecan in patients with previously treated metastatic colorectal cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C057. doi:10.1158/1535-7163.TARG-19-C057

Bendamustine-Rituximab Does Not Improve Survival over Rituximab Monotherapy for Older Patients with Nodal or Splenic Marginal Zone Lymphoma

Background: Nodal and splenic marginal zone lymphomas (NMZL/SMZL) are rare, usually disseminated, and typically diagnosed in older patients (median age 69 years). They are increasingly treated with first-line bendamustine/rituximab (BR) based on phase 3 trials that pooled various B-cell indolent lymphomas (Rummel et al., Lancet 2013). However, NMZL and SMZL have unique biology and clinical course. In this context, without histology-specific evidence, the risk/benefit ratio of BR over single-agent rituximab (R) in SMZL/NMZL is uncertain. Our objective was to examine treatment patterns, and to compare survival and toxicity outcomes of BR versus (vs.) R, using population-based data. Methods: Using Medicare claims linked to cancer registry data covering ~34% of the US population (SEER-Medicare), we identified all SMZL/NMZL patients age ≥65 who received 1st line R or BR between 2009-2016 (after approval of bendamustine) and had complete Medicare records. We used a propensity score to generate "pseudo-randomized" cohorts (pooled, including NMZL and SMZL, and histology -specific for NMZL and SMZL), balancing patient and disease characteristics: age, sex, race, comorbidities (including kidney disease and heart failure), performance status, lymphoma stage, B symptoms, prior splenectomy, anemia (including autoimmune hemolytic), transfusions, hospitalizations, and time from diagnosis to therapy. In the balanced pseudo-randomized cohorts, we compared event-free survival (EFS, defined as 2nd line chemotherapy, splenectomy, hospice, or death) and overall survival (OS) from the start of therapy, risk of major toxicities (hospitalization, transfusions), and inflation-adjusted Medicare spending. Outcome models report hazard ratios (HR) or risk ratios (RR) with 95% confidence intervals (95%CI), and marginal means for costs. Results: Among 1,315 patients (901 with NMZL and 414 with SMZL), median age was 78 years [y], and there were 52% women. About half of patients received first-line R every year, but the proportion treated with BR increased from 4% in 2009 to 23% in 2016 (Fig. A). In the pooled NMZL/SMZL cohort of patients receiving BR or R (N=926), those treated with BR were on average younger, more likely to have NMZL, stage 2-4 lymphoma, and B symptoms. With median follow-up 3.8 y, median EFS was 4.3 y (95%CI, 3.5-5.1) for NMZL, and 4.5 y (95%CI, 3.8-6.5) for SMZL. Median OS was 5.7 y (95%CI, 4.9-6.7) in NMZL, and 5.2 y (95%CI, 4.4-6.7) in SMZL. After balancing the confounders, there was no significant difference in either EFS (HR for BR, 1.00; 95%CI, 0.76-1.30, P=.98) or OS (HR, 1.14; 95%CI, 0.85-1.53; P=.38). Toxicities were higher with BR, including hospitalizations (RR, 1.46; 95%CI, 1.14-1.87; P=.003) and transfusions (RR, 2.35; 95%CI, 1.55-3.56; P<.001). Mean Medicare spending within 1 year from diagnosis was higher after BR (mean $83,480) than R (mean $53,776; P<.001). A sensitivity analysis showed that >50% of BR patients would need to have an unobserved risk factor doubling their mortality to explain lack of OS benefit. We then fitted separate propensity score models in NMZL and SMZL. In the comparative NMZL cohort (N=609), 434 patients (71%) received R, and 175 (29%) received BR. We observed no significant difference in either EFS (HR for BR, 0.93; 95%CI, 0.68-1.29; P=.67; Fig. B) or OS (HR, 1.16; 95%CI, 0.82-1.63; P=.40), whereas toxicities and costs were consistently higher with BR. In the comparative SMZL cohort (N=317), 272 patients (86%) received R, and 45 (14%) received BR. Again, there was no significant difference in EFS (HR for BR, 0.84; 95%CI, 0.46-1.53; P=.56; Fig. C) or OS (HR, 0.92; 95%CI, 0.46-1.83; P=.80). Results for toxicities and costs were again consistent. Conclusions: Among older patients with SMZL and NMZL treated in the community, the use of first-line BR is increasing. However, in this large observational study, BR was not associated with any significant EFS or OS benefit over single-agent R, while it increased toxicities and costs. Without a formal randomized histology-specific study, single-agent R may offer a favorable risk/benefit ratio as a first-line therapy for older NMZL/SMZL patients at average risk, reserving BR for those with compelling clinical circumstances. Our results may however be affected by bias due to unobserved confounding, and may not be applicable to younger patients. Disclosures Olszewski: Adaptive Biotechnologies: Research Funding; Genentech: Research Funding; TG Therapeutics: Research Funding; Spectrum Pharmaceuticals: Research Funding. OffLabel Disclosure: Rituximab with bendamustine is off-label for marginal zone lymphoma

Current Treatment Patterns and Outcomes in Patients with Peripheral T-Cell Lymphoma: Updated Results of the Nationwide, Multi-Center Prospective Registry Study (CISL 1404)

Introduction Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of diseases associated with poor prognosis, representing 10-15% of non-Hodgkin lymphomas. Although CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like regimens are often preferred as 1st line treatment, the treatment outcome is poor with 5-year overall survival (OS) rate of 30-40%. In an effort to improve the survival outcomes of these patients, autologous hematopoietic stem cell transplantation (ASCT) as an upfront consolidative treatment has been proposed for patients achieving partial or complete remission after induction therapy. However, the role of ASCT still remains undefined since no randomized trials have demonstrated survival benefit of ASCT in this setting. To better understand the clinical characteristics, treatment patterns, and outcomes in patients with PTCL, we have conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with PTCL. Methods Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored (ClinicalTrials.gov, no. NCT02364466). All patients were pathologically diagnosed with PTCL according to the 2008 World Health Organization classification of lymphoid neoplasms. Extranodal NK/T cell lymphoma, cutaneous T cell lymphoma, Mycosis fungoides and Sezary syndrome were excluded. The target number for enrollment was 200, and an interim analysis was previously reported at the time of enrollment of 155 patients (ASH 2017). An updated analysis of 198 patients was performed. Results The median age was 59 years (range, 49-70), 122 patients (61.6%) were male and 168 (84.9%) had ECOG performance status of 0-1. PTCL, not otherwise specified was the most common pathologic subtype (n = 80, 40.4%), followed by angioimmunoblastic T cell lymphoma (n = 60, 30.3%). The most frequently administered 1st line regimen was CHOP or CHOP-like regimen (n = 165, 83.3%), followed by ICE (ifosfamide, carboplatin, and etoposide) or ICE-like regimen (n = 23, 11.6%), and others (n = 10, 5.1%). With a median follow-up duration of 28.2 months (95% CI, 25.6-30.6), 2-yr progression-free survival (PFS) rate was 44.4% (95% CI, 37.5-57.4) and 2-yr OS rate was 64.4% (95% CI, 57.4-72.1). Response evaluation for 1st line regimens were available in 175 patients. Among these patients, there was no significant difference in overall response rate (ORR) and complete response (CR) rate between patients treated with CHOP or CHOP-like vs. ICE or ICE-like regimen (ORR: 73.6 vs. 72.7%, P = 1.000; CR rate: 58.1% vs. 45.5%, P = 0.375). In addition, no significant difference was observed regarding PFS and OS between the two treatment groups (CHOP or CHOP-like vs. ICE or ICE-like; 2-yr PFS rate: 45.2 vs. 38.3%, P = 0.39; 2-year OS rate: 65.7 vs. 50.7% P = 0.43) (Figure 1A, B). Among 121 patients younger than 65 years of age who are eligible for transplantation, autologous hematopoietic stem cell transplantation (ASCT) was performed as an upfront consolidative treatment in 51 patients (42.1%). Patients who received upfront ASCT was associated with significantly better PFS and OS compared with patients who did not, with a 2-yr PFS rate of 52.3 vs. 37.0% (P = 0.032) and 2-yr OS rate of 74.2 vs. 57.1% (P = 0.028), respectively (Figure 2A, B). A total of 81 patients were treated with 2nd line chemotherapy for refractory or relapsed disease, and response evaluation for 2nd line chemotherapy was available in 63 patients. Among these patients ORR and CR rate were 49.2% and 30.2%, respectively. Conclusion Our study demonstrated that survival outcome with current treatment options for patients with PTCL remains poor. Although CHOP or CHOP-like regimens were the most commonly used 1st line regimens, no survival benefit was observed when compared with ICE or ICE-like regimens, suggesting that more efforts are needed to establish a standard 1st line treatment for PTCL. ASCT may provide survival benefit in transplant eligible patients, which warrants further evaluation in randomized controlled trials. Disclosures Yoon: Janssen: Consultancy; MSD: Consultancy; Novartis: Consultancy, Honoraria; Yuhan Pharma: Research Funding; Amgen: Consultancy, Honoraria; Genentech, Inc.: Research Funding; Kyowa Hako Kirin: Research Funding. Kim:F. Hoffmann-La Roche Ltd: Research Funding; Celltrion: Research Funding; Novartis: Research Funding; Donga: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; J + J: Research Funding.

167P - Prognostic impact of the C-reactive protein/albumin ratio in advanced pancreatic cancer treated with GEM plus nab-PTX or FOLFIRINOX: Based on the results of a multicenter retrospective study (the NAPOLEON study)

BackgroundGEM plus nab-PTX (GnP) and FOLFIRINOX (FFX) have been shown to improve overall survival for advanced pancreatic cancer patients. However, clinical utility of C-reactive protein/albumin ratio (CAR) as prognostic factor for the patients treated with GnP or FFX remains unclear. We conducted the exploratory analysis to elucidate prognostic impact of CAR using a multicenter retrospective study (the NAPOLEON study) cohort which examined the efficacy and safety of GnP and FFX in clinical practice. MethodsBetween December 2013 to March 2017, 255 patients with unresectable advanced or recurrent pancreatic cancer who received GnP or FFX as 1st-line chemotherapy at 14 centers participating in the NAPOLEON study were examined. Patient characteristics at the start of 1st and 2nd line chemotherapy including age, gender, ECOG performance status, primary tumor site, disease status, metastatic site, underwent biliary drainage or not, treatment regimen at 1st line chemotherapy, LDH and CAR were analyzed to investigate correlation with prognosis by Cox regression model. The cut-off value of CAR adopted 0.54 based on a previous study. Patients were divided into groups according to CAR level less than 0.54 (CAR-low) and 0.54 or greater (CAR-high). ResultsCox regression analysis of OS identified underwent biliary drainage (HR: 1.76, 95%CI: 1.19–2.61), CAR-high (HR: 1.52, 95%CI: 1.05–2.21), and higher LDH level (HR: 2.10, 95%CI: 1.36–3.22) as significant factors at the start of 1st-line chemotherapy. Similarly, Cox regression analysis of OS identified a poor PS (HR: 1.62, 95%CI: 1.07–2.47), a high level of CA19-9 (HR: 2.14, 95%CI: 1.07–4.29) and CAR-high (HR: 2.15, 95%CI: 1.32–3.49) as significant factors at the start of 2nd-line chemotherapy. Eighty-six of 140 patients (82.7%) with CAR-high at the start of 1st-line chemotherapy still remained CAR-high at the start of 2nd-line chemotherapy. ConclusionsCAR may be useful prognostic factor at the start of both 1st and 2nd-line treatment. Almost all the patients with CAR-high before 1st line treatment still remained CAR-high after 1st line treatment. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

490P - Outcomes of sequential epidermal growth factor receptor tyrosine (EGFR) tyrosine kinase inhibitor (TKI) therapy in patients with advanced non-small cell lung carcinoma (NSCLC)- a real-world institutional experience

BackgroundEGFR T790M mutations have been reported to occur in about 50% of patients (pts) at progression on 1st/2nd generation EGFR TKI therapy. These pts benefit from treatment with 3rd generation EGFR TKI osimertinib. However, observational real-world studies show that the proportion of pts receiving 2nd line osimertinib is lower than expected. We aimed to evaluate these treatment patterns and outcomes in our institution. MethodsIn this prospective observational study, survival, response and treatment data was collected from pts with EGFR mutant advanced NSCLC who received EGFR TKIs in the 1st line, who were treated in our institution from September 2012 to December 2017. Institutional approval was obtained and all patients provided written, informed consent. Results108 pts (median age 65 years, 54% females, 75% never smokers, 54% EGFR exon 19 deletion) were enrolled of whom 48 (44%) received gefitinib, 38 (35%) erlotinib and 22 (20%) afatinib in the 1st line. The median overall survival (OS) was 33.1 months (95% CI 24.5-41.7) and median progression free survival (PFS) was 11.1 months (95% CI 8.5-13.7). 83 pts (77%) had progressed at the time of analysis, and 48/83 patients (58%) underwent T790M testing. Of these, 25/48 (52%) were T790M positive. 21/83 pts went on to receive osimertinib in the 2nd line (25% of all patients who progressed on 1st line therapy)- OS was not reached in these pts. 12/83 pts received 2nd line chemotherapy (15%); 32/83 pts (39%) did not receive any 2nd line treatment. OS was 42.3 months (95% CI 24.2-50.4) and 18.2 months (95% CI 11.6-24.7) in these groups respectively. ConclusionsIn this prospective real-world study, a significant proportion of patients did not receive 2nd line therapy after progression on 1st/2nd generation TKIs. The rates of T790M mutations when tested was comparable to that reported in the literature. Some reasons for not receiving 2nd line therapy included low testing rates for EGFR T790M and patient fitness for 2nd line therapy. This suboptimal use of osimertinib in the 2nd line setting, together with favourable PFS data for osimertinib in the 1st line, favours the upfront use of osimertinib. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureC.S. Tan: Honoraria (self): AstraZeneca; Honoraria (self): Merck; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Novartis; Honoraria (self): Eli-Lilly; Honoraria (self): Eisai; Honoraria (self): BMS. R.A. Soo: Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self): BMS; Honoraria (self), Research grant / Funding (self): Boehringer Ingelheim; Honoraria (self): Celgene; Honoraria (self): Ignyta; Honoraria (self): Lilly; Honoraria (self): Merck; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): Taiho; Honoraria (self): Takeda; Honoraria (self): Yuhan. All other authors have declared no conflicts of interest.

621P - Biweekly TAS-102 and bevacizumab as a third-line chemotherapy for metastatic colorectal cancer: A phase II multicenter clinical trial (TAS-CC4 study)

BackgroundTAS-102 improved overall survival of metastatic colorectal cancer (mCRC) patients with median progression-free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, the combination of TAS-102 and bevacizumab (BV) has been shown to extend median PFS to 3.7 months (C-TASK FORCE). However, this study included patients with 2nd line and 3rd line chemotherapy. Furthermore, combination chemotherapy of TAS-102 plus BV was reportedly associated with grade ≥3 neutropenia in 72% of treated patients. This study was designed for patients being treated as 3rd line chemotherapy to investigate the clinical impact of this combination and whether neutropenia could be suppressed by altering the TAS-102 administration protocol (biweekly method). MethodsThis phase II study was conducted in investigator-initiated, open-label, single-arm, multicenter manner in Japan. Eligible patients were 20-80 years old and had to have an ECOG performance status of 0 or 1; had confirmed unresectable mCRC with histologically diagnosed adenocarcinoma; had previously administrated first- and second-line chemotherapy for mCRC and whose tumors were diagnosed as progression of disease (PD). TAS-102 (35mg/ m²) was given orally twice daily on days 1 -5 and 15 -19 in a 4-weeks cycle, and BV (5mg/ kg) was administered by intravenous infusion for 30min in every 2 weeks. The primary endpoint was PFS, and the secondary endpoints were response rate (RR), disease control rate (DCR), overall survival (OS), and safety. This study was registered at the University Hospital Medical Information Network, as UMIN#000030030. ResultsBetween January 1, 2018, and March 31, 2019, 45 patients with mCRC were enrolled in this study (median age, 63; male, 51%). The median PFS was 121 days. The RR and DCR were 4.4% and 73.3%, respectively. Grade 3 or higher adverse events were hypertension (20.0%), neutropenia (15.5 %), leukopenia (6.7 %), fatigue (6.7 %), anemia (4.4 %), anorexia (2.2 %), nausea (2.2 %), creatinine increased (2.2 %) and proteinuria (2.2 %). No treatment-related deaths occurred. ConclusionsBiweekly administration of TAS-102 and BV prevents neutropenia and could be one of the treatment options for 3rd line chemotherapy for mCRC. Clinical trial identificationUMIN000030030. 2018/March/01. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

The comparison of Carfilzomib, and dexamethasone versus pomalidomide-based combination chemotherapy after a 2nd-line therapy in relapsed and refractory multiple myeloma patients

New class of drugs are emerging in heavily pretreated patients in clinical trials, carfilzomib, and dexamethasone (Kd) and pomalidomide and dexamethasone with or without cyclophosphamide (Pd or PCd) are still important options for treatment of relapsed and/or refractory multiple myeloma (RRMM). However, direct comparison of the efficacy of carfilzomib and pomalidomide has not been evaluated. The aim of this study was to compare the efficacy and safety profile of Kd and pom-based regimens in RRMM patients after 2nd line chemotherapy in the real world clinical setting. Patient and method: Two-hundred and twenty-five patients from 14 hospitals participating in the Korean multiple myeloma working party (KMMWP) were retrospectively analyzed by review of medical records. Multiple myeloma patients who relapsed or were refractory to 2 or more lines of chemotherapy regimens and who had been treated with Kd (Kd group, N=44) or pomalidomide-based chemotherapy (Pom group, N=181) were included. When patients who had been administered with both carfilzomib and pomalidomide-combination chemotherapies sequentially, the drug used in advance was analyzed. The pomalidomide group included patients who had undergone Pd (N=108) and PCd (N=73).

P1.01-15 Multicenter, Single-Arm Phase II Study of Nab-Paclitaxel/Carboplatin in Untreated PS2 Patients with Advanced NSCLC: TORG1426

Performance Status (PS) has been shown to predict survival in patients with advanced non-small cell lung cancer (NSCLC). To date, PS2 patients have been underrepresented in clinical trials due to concerns about tolerability. Consequently, no standard of care exists for these patients. In CA031 trial, nab-paclitaxel/carboplatin (nab-PTX/CBDCA) demonstrated significantly higher response rate (RR) compared with PTX/CBDCA in PS0-1 patients with advanced NSCLC. Furthermore, in elderly subgroup, nab-PTX/CBDCA tended to show superior progression-free survival (PFS) and overall survival (OS) based on better tolerability compared with PTX/CBDCA. Therefore, this phase II trial was designed to characterize the efficacy, safety, and tolerability of nab-PTX/CBDCA in untreated PS2 patients with advanced NSCLC. Chemotherapy-naive PS2 patients with stage IIIB/IV NSCLC were treated with nab-PTX (70 mg/m2 on day1, 8, and15, q4w) and CBDCA (AUC 5 on day1, q4w) up to 6 cycles if they did not have uncontrolled brain metastasis or pleural effusion. The primary endpoint was PFS rate at 6 months. Its achievement of more than 50% was considered worthy of further development of this regimen, whereas that of less than 30% was considered insufficient for further investigation. The estimated power was 80% with type I error of 0.05, resulting in 35 patients needed. Concurrently, Symptom Score and Charlson Comorbidity Index (CCI) were evaluated. This trial was terminated due to slow accrual. Between September 2015 and August 2018, 17 patients (median age, 68 years [range, 50-73]) were enrolled and received a median of 3 cycles. The reasons for PS2 were tumor progression (71%), comorbidities (12%), or both (17%). The PFS rate at 6 months was 20.8% (95% confidence interval, 0%-41.6%). The median PFS, OS, RR, and disease control rate (DCR) were 3.0 months, 9.5 months, 17.4%, and 70.6%, respectively. Grade 3-5 adverse events (AE) included fatigue (24%), lung infection (24%, including 6% of grade 5), neutropenia (18%), and anemia (18%), resulting in trial withdrawal rate of 24%. The median PFSs of 11 patients with and 6 patients without 2nd line chemotherapy were 5 months and 1.7 months, respectively (p = 0.009). Symptom Score was improved by chemotherapy (p = 0.004), whereas comparison between lower and higher CCI values demonstrated no difference regarding chemotherapy cycles administered (p = 0.5) and regarding chemotherapy efficacy (p = 0.268). Nab-PTX/CBDCA did not meet its primary endpoint but could be a feasible treatment option for untreated PS2 patients with advanced NSCLC. Clinical trial information: UMIN000019458

UNUSUAL CASE OF DIFFUSE CYSTIC LUNG DISEASE

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Cystic lung disease is a group of heterogeneous pulmonary diseases resulting from hereditary/congenital, systemic disorders and infectious causes among others. Malignancy is not a usual cause of cystic lung disease. We present a case of pulmonary mucinous cystadenocarcinoma (PMC) that presented as cystic lung disease. CASE PRESENTATION: Sixty six year old male former smoker was admitted in May 2018 with cough and dyspnea. Examination revealed rhonchi bilaterally. Chest radiograph revealed bilateral diffuse patchy alveolar infiltrates prompting Chest CT scan that revealed alveolar consolidations and numerous cavitary lesions with mediastinal and hilar lymphadenopathy. Bronchoscopy with lavage yielded Streptococcus pneumoniae with negative cytology for malignancy. He was treated with antibiotics with minimal improvement. He was subsequently seen at pulmonary office and had extensive collagen vascular serology tests, which were negative. He underwent repeat bronchoscopy including EBUS-TBNA of paratracheal lymph nodes, which was non-diagnostic. Having reported 40-pound weight loss he underwent robotic right upper lobe biopsy that revealed well-differentiated mucinous adenocarcinoma, which was EGFR/ALK negative. He later had biopsy of left lower lobe after extensive discussion at tumor board, which showed the same pathology. PET CT showed multiple bilateral cavitary lesions with no hypermetabolic activity. He was treated with carboplatin-based chemotherapy. Repeat chest CT after two treatments showed marked progression of innumerable cavitary metastatic lesions throughout both lungs, with tumors coalescing, and new extensive ground glass infiltrates. Oncology is presently considering 2nd line chemotherapy. DISCUSSION: PMC is a very rare type of lung cancer in the colloid adenocarcinoma spectrum that was initially described by Gowar in 1978. It commonly involves bilateral lower lobes and is commonly uni- or oligolocular unlike our case although multicystic PMC is not unusual. The incidence of PMC’s is unknown probably due to it’s rare nature with a 2011 publication reporting that only 20 cases were documented then. Diagnosing PMC can be an extremely challenging since bronchoscopy with BAL/washing/Transbronchial biopsy and FNA are often inconclusive probably due to malignant cells usually floating in the mucin. Furthermore mucinous adenocarcinoma tumor cells and submucosal mucinous glands of bronchial tissue can mimic each other morphologically. Therefore diagnosis is usually made by surgical biopsy. FDG PET activity may vary but tend to be low. Biological behavior of PMC is unknown with limited data suggesting low malignancy potential unlike our case. Treatment and natural history of PMC is unclear. CONCLUSIONS: This case illustrates the importance of maintaining a broad differential diagnosis. Reference #1: Gowar FJS. An unusual mucous cyst of the lung. Thorax. 1978;33:796–799. https://doi.org/10.1136/thx.33.6.796. DISCLOSURES: No relevant relationships by Pius Ochieng, source=Web Response No relevant relationships by Ajay Shetty, source=Web Response No relevant relationships by Pandi Todhe, source=Web Response

P2.14-57 Efficacy of 3rd Generation EGFR-TKIs After Failing First or Second Generation EGFR-TKIs in EGFR Mutation-Positive NSCLC (ROOT-EGFR)

Over the past decade, treatment of EGFR mutation –positive NSCLC has been revolutionized with the development of next generation EGFR TKIs. Four epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), erlotinib, gefitinib, afatinib and osimertinib, are currently available in Korea. Recent trials have compared the available and emerging EGFR TKIs head to head. The highly anticipated findings of the phase III FLAURA trial showed a nearly doubling of PFS with frontline osimertinib, a third-generation TKI, versus erlotinib or gefitinib. The optimal sequence of EGFR TKIs is still controversial. And many countries 3rd generation EGFR TKI is not readily available. The purpose of this study is to analyze the efficacy in patients who received first-line gefitinib, erlotinib, or afatinib and followed by 3rd generation EGFR-TKIs. This non-interventional observational study through big data analysis will retrospectively collect de-identified patient data from clinical data warehouse (CDW) using a unique algorithm with Standard Query Language (SQL) called ROOT project. Over 10 years, 2,358 patients were diagnosed recurrent or metastatic non-small cell lung cancer and received 1st or 2nd generation EGFR TKIs at Samsung Medical Center. 72.9% (1720/2358) of EGFR mutation-positive NSCLC patients received 1st or 2nd generation EGFR-TKIs as first line palliative chemotherapy. In total population, 30.8% (727/2358) patients received 3rd generation EGFR TKIs. Among them, patients who received 3rd generation EGFR TKI after 1st or 2nd generation EGF TKIs showed better overall survival (45.0 months (95% CI, 41.8-48.2). Among 1720 patients who received 1st or 2nd generation EGFR-TKIs as first line palliative chemotherapy, 313 patients received 3rd generation EGFR-TKIs as 2nd line chemotherapy and 200 patients received as more than 3rd line chemotherapy. However, there was no difference of overall survival between them (44.0 months vs 47.0months, p-value=0.104). This study was meaningful as a study of what can be the best sequence in EGFR-TKI treatment. Updated and detail clinical and exploratory biomarker outcome will be presented at the meeting.

925P - Analysis of response to prior therapies and therapies after treatment with erdafitinib in fibroblast growth factor receptor (FGFR)-positive patients (pts) with metastatic urothelial carcinoma (mUC)

BackgroundRecently, erdafitinib (erda), a novel FGFR-targeted therapy received accelerated US FDA approval for locally-advanced or mUC in adult pts with FGFR2/3 alterations who progressed on prior 1st-line platinum-containing chemotherapy. The current analysis was performed to understand treatment response to prior and subsequent therapies in FGFR+ mUC pts treated with erda. MethodsPts with surgically unresectable mUC who had failed ≥1 prior chemotherapy and received 8mg once-daily erda in a phase 2 study (NCT02365597) were retrospectively assessed. Pts were grouped as cisplatin (C)-eligible (received 1st-line gemcitabine [G]-C or MVAC [methotrexate/vinblastine/doxorubicin/C]) or C-ineligible (received 1st-line G-carboplatin or checkpoint inhibitors). Treatment duration, time to progression (TTP) and response to prior chemotherapy (objective response rate [ORR] and disease control rate [DCR]), progression-free survival (PFS), overall survival (OS), and subsequent response after erda therapy were assessed using investigator reported outcomes. ResultsIn this analysis, the median duration of treatment (time from 1st dose of 1st line to 1st dose of 2nd line) with 1st-line chemotherapy was 10.07 months for C-eligible (n=52) and 8.02 months for C-ineligible (n=34) pts; 31 pts received prior 2nd-line chemotherapy (median treatment duration: 9.23 months) and 10 received 3rd-line chemotherapy (median treatment duration: 6.26 months). The median TPP for prior 1st-line therapy was longer than on 2nd or 3rd-line therapy (Table). In total, 34 patients received treatment (chemotherapy, n=19; immunotherapy, n=15) after erda and had median PFS of 2.27 months (95% CI: 0.79; 2.86) and median OS of 3.52 months (95% CI: 2.04; 8.90).Table925P Efficacy results on prior and subsequent treatmentsTablePrior therapyMedian TTP (95% CI), monthsORR (CR+PR) (%)DCR (CR+PR+ SD) (%)1st-line chemotherapy (n=84)7.34 (5.91; 8.80)28/84 (33.3)49/84 (58.3)C-eligible8.84 (6.37; 10.38)18/52 (34.6)31/52 (59.6)C-ineligible6.59 (3.06; 7.49)9/34 (26.5)18/34 (52.9)2nd-line chemotherapy (n=31)7.13 (3.78; 9.36)11/31 (35.5)21/31 (67.7)2nd-line D/V/P7.13 (3.06; 10.48)6/16 (37.5)10/16 (62.5)3rd-line chemotherapy (n=10)5.70 (2.33; 8.64)2/10 (20.0)5/10 (50.0)3rd-line D/V/P5.55 (2.99; 9.46)1/7 (14.3)3/7 (42.9)Therapy after erda (n=34)ORR (%)DCR (%)1st-line after erda1/34 (2.9)3/34 (8.8)1st-line chemotherapy0/160/161st-line immunotherapy1/15 (6.7)3/15 (20.0)2nd-line after erda1/9 (11.1)1/9 (11.1)2nd-line chemotherapy0/70/72nd-line immunotherapy1/2 (50.0)1/2 (50.0)CR, complete response; D/V/P, docetaxel/vinflunine/paclitaxel; PR, partial response; SD, stable disease. ConclusionsThese results provide insights into treatment responses in a unique population of FGFR+ mUC pts. Clinical trial identificationNCT02365597. Editorial acknowledgementPriya Ganpathy, MPharm, ISMPP CMPP™ (SIRO Clinpharm Pvt. Ltd., India) provided writing assistance and Harry Ma, PhD (Janssen Global Services, LLC) provided additional editorial support. Legal entity responsible for the studyJanssen Research & Development, LLC. FundingJanssen Research & Development, LLC. DisclosureA.O. Siefker-Radtke: Advisory / Consultancy: Janssen, Threshold Pharmaceuticals, Merck, National Comprehensive Cancer Network, Eisai, Genentech, Vertex, AstraZeneca, EMD Serono, Bristol-Myers Squibb; Research grant / Funding (self): National Institutes of Health, Genentech, Janssen Pharmaceuticals, Millennium, Michael and Sherry Sutton Fund for Urothelial Cancer; Speaker Bureau / Expert testimony: Genentech. B. Zhong: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. K. Qi: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. W.S. Shalaby: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. P. De Porre: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. A. O’Hagan: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development, LLC. P. Mahadevia: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. Y. Loriot: Advisory / Consultancy: Astellas Oncology; AstraZeneca; Ipsen; Janssen; MSD; Roche; Sanofi; Research grant / Funding (self): Sanofi (Inst); Travel / Accommodation / Expenses: AstraZeneca; MSD; Roche.

913PD - APACHE: An open label, randomized, phase II study of durvalumab (Durva), alone or in combination with tremelimumab (Treme), in patients (pts) with refractory germ cell tumours (GCT): Results from the expanded combination therapy cohort

BackgroundInterim results from APACHE (NCT03081923) have been presented, with the monotherapy arm stopped for futility (Necchi, Eur Urol 2018). Updated results with the expanded combination therapy cohort are presented. MethodsApache is an open-label, randomized, 3-stage, phase 2 study. Pts who have failed ≥2 chemotherapy (CT) regimens received Durva, 1.5gr q4w, x 13 cycles (arm A) or Durva plus with Treme, 75mg q4w, x 4 cycles, followed by Durva alone x total 13 cycles (arm B). The primary endpoint is the modified objective response-rate (mORR=RECIST 1.1 complete or partial response [PR] or stable disease [SD]+STM reduction >10%). H0: mORR rate ≤10%, H1: mORR ≥25% (α and β=10%). The total sample size of 120 pts is split into 3 stages: in stage 1, each arm is terminated whenever no response is observed in 11 pts/arm. In stage 2, 29 additional pts/arm are enrolled. Biomarker analyses include: PD-L1 expression on immune cells (Ventana SP142) and comprehensive genomic profiling (CGP) with FoundationOne assay. ResultsFrom 02/17-11/18, 29 pts were enrolled (11 arm A and 18 arm B). 22 had gonadal and 7 extragonadal GCT, 19 had received >/=3 prior CT regimens. Median tumour mutational burden (TMB) was 4 mutations (mut)/mb, 1pt showed microsatellite instability in arm A. 10 pts (34.5%) experienced any-Grade AEs, without differences between arms. In the expanded arm B, 2 responses (11.1%, 1 RECIST-PR in seminoma and 1 SD with STM reduction in nonseminoma) and 2 SD were observed. PD occurred regardless of PD-L1 expression and TMB. After median follow-up of 16.3 months, 12-month OS in arm A was 30% (95%CI: 7.2-57.7) and in arm B was 29.6% (95%CI: 10.2-52.2). Further CT post-PD was administered in 8 pts (27.6%), but was mostly ineffective (7/8 SD/PD). ConclusionsDespite objective responses were rare with IO, long-term OS results are encouraging in very highly pre-treated GCT pts, suggesting a role for maintenance approach in earlier setting (2nd-line CT), and privileging Durva+Treme due to more responses. Conventional IO biomarkers did not allow for patient selection, and further research is warranted. Clinical trial identificationNCT03081923. Legal entity responsible for the studyAstraZeneca. FundingAstraZeneca. DisclosureS.M. Ali: Full / Part-time employment: Foundation Medicine. J. Chung: Full / Part-time employment: Foundation Medicine. J.S. Ross: Full / Part-time employment: Foundation Medicine. A. Necchi: Honoraria (institution), Advisory / Consultancy: Merck; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy, Spouse / Financial dependant: Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy: Clovis; Honoraria (institution), Advisory / Consultancy: Janssen; Honoraria (institution), Advisory / Consultancy: Roche. All other authors have declared no conflicts of interest.

The clinical efficacy of eribulin to soft tissue sarcoma patients: differences in histological subtypes

Abstract Background In Japan, eribulin can be indicated to all histology of STS and available as 2nd or later line chemotherapy; however, the clinical evidence of eribulin to STS based on the international randomized clinical trial is limited to L-sarcoma (leiomyosarcoma and liposaroma) as 3rd or later line chemotherapy yet. Methods We retrospectively reviewed STS patients treated with eribulin between March 2016 and December 2018 in our institute. Prognoses of all patients, differences of prognoses by histology (comparison of L-sarcoma and other histology) and differences of prognoses by treatment line (comparison of 2nd line and later line) in L-sarcoma were evaluated. Results Total of 41 patients were enrolled in the analysis; 26 of them were L-sarcoma and 15 were other histology. In 26 L-sarcoma patients, 12 patients was leiomyosarcoma and the other 14 was liposarcoma. Among L-sarcoma patients, the media PFS was longer in liposarcoma (8.42 months, 95% CI: 5.67-11.17) than leiomyosarcoma (2.3 months, 95% CI: 1.35-3.32) significantly (p = 0.021), but there were not differences in the median OS between liposarcoma (24.4 months, 95% CI: 6.14-42.59) and leiomyosarcoma (21.90 months, 95% CI: 0.76-43.03) significantly (p = 0.568). Conclusion Eribulin showed longer prognoses in L-sarcoma, especially in liposarcoma in terms of the PFS.

3246 Long-Term Survival in a Patient With Recurrent Gastric Cancer With Peritoneal Seeding Undergoing Chemotherapy and Mistletoe Extract Treatment

INTRODUCTION: Recurrent gastric cancer with peritoneal seeding is associated with poor overall survival. Mistletoe extract has been widely used for complementary cancer therapy such as pancreatic cancer, ovarian cancer, and melanoma which support the quality of life and prolong overall survival. However, the effect of treatment for recurrent gastric cancer remains controversial. CASE DESCRIPTION/METHODS: A 71-year-old man with advanced gastric cancer underwent radical total gastrectomy (stage IIIb, T4b N1 M0). Abdominopelvic computed tomography performed 7 months after surgery revealed the increased ascites with an enhanced peritoneal thickening. He was diagnosed with peritoneal seeding and received 2nd line chemotherapy (Irinotecan). However, he was refused the chemotherapy due to side effects after 1 cycle. He starts receiving alternative therapy with Viscum album extract (mistletoe) instead of chemotherapy. Malignant ascites had decreased gradually after mistletoe extract therapy. So we start 3rd line chemotherapy (docetaxel) with mistletoe extract. The patient achieved good health with complete response postoperative 32 months after combination treatment. The patient has survived for 51 months after surgery without disease progression. We report a case of recurrent gastric cancer with peritoneal seeding that was successfully treated by docetaxel monotherapy with long-term mistletoe extract treatment. DISCUSSION: Mistletoe extract contributed to the reduction of malignant ascites and improved quality of life during chemotherapy. This case suggests that the synergistic effect of mistletoe extract treatment could be expected when used together with chemotherapy for recurrent gastric cancer.