Second-line Systemic Therapy Research Articles

Real-world systemic sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Korea.

Background/Aims Regorafenib has been approved as a second-line systemic therapy for hepatocellular carcinoma (HCC) patients after the phase III RESORCE trial. This study analyzed real-world data to assess the clinical effectiveness and safety of regorafenib compared to the RESORCE trial.MethodsThis multicenter cohort study included HCC patients treated with regorafenib after sorafenib (n = 133). We evaluated the time to progression (TTP), progression-free survival (PFS), overall survival (OS), and safety in patients receiving regorafenib along with the predictors of prognosis.ResultsThe median age was 60years and 81.2% patients were men. Hepatitis B virus infection (68.4%) was the commonest etiology. Most patients were classified as Child-Pugh A (98.5%) and had extrahepatic metastasis (84%) and vascular invasion (45.1%). This study demonstrated similar characteristics apart from more frequent hepatitis B etiology and more vascular or extrahepatic involvement compared with the RESORCE trial. An objective response rate of 12.5% was obtained for response assessment (n = 112); the disease control rate was 34.8%. Thirty-eight patients died during follow-up. With regorafenib, the median OS, PFS, and TTP were 10.0, 2.7, and 2.6 months, respectively. In the exploratory analysis after sorafenib administration, the median OS was 25.8months. The rate of response and survival were comparable to those in the RESORCE trial. Child-Pugh score > 5, alpha-fetoprotein > 400ng/ml, and TTP for sorafenib ≥ median were independently associated with OS.ConclusionsThis real-word regorafenib study showed comparable effectiveness and safety to the RESORCE trial. Regorafenib improves the prognosis of patients with prolonged TTP during previous sorafenib therapy.

NCCN Guidelines Insights: Cervical Cancer, Version 1.2020.

The NCCN Guidelines for Cervical Cancer provide recommendations for diagnostic workup, staging, and treatment of patients with the disease. These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to first- and second-line systemic therapy recommendations for patients with recurrent or metastatic disease, and emerging evidence on a new histopathologic classification system for HPV-related endocervical adenocarcinoma.

Omalizumab in three children with severe vernal keratoconjunctivitis

SummaryBackgroundVernal keratoconjunctivitis (VKC) is a rare, recurrent form of ocular allergy that can be refractory to topical and systemic treatment. It typically presents as acute and chronic keratoconjunctival inflammation that may lead to visual impairment due to corneal ulcers and scaring. Patients often suffer from atopic IgE-driven comorbidities, especially atopic eczema. Children are frequently affected and often do not tolerate topical treatment well, especially if photophobia and pain impair therapy adherence. We present three children with severe VKC who were not controlled by first- and second-line topical and systemic therapy and finally responded to treatment with the monoclonal anti-IgE antibody omalizumab as third-line treatment.Methods and resultsWe retrospectively analyzed three patients with VKC having failed response to first- and second-line treatment. All three boys had very early allergic rhinoconjunctivitis from age 1–3 with polysensitization: birch, grass pollen, house dust mite, and/or pets. All received subcutaneous or sublingual immunotherapy (SCIT/SLIT) for birch and/or grass pollen without major success. Two patients had comorbidities: allergic asthma and severe atopic dermatitis (AD). For at least 6 months after the first administration, monoclonal anti-IgE antibody omalizumab (150 or 300 mg) was administered subcutaneously every 2–6 weeks in all patients achieving improvement of the clinical grading scale from VKC grade 3–4 to grade 1–2. One patient had a relapse mainly of his AD and achieved complete control of AD and VKC by introduction of dupilumab.ConclusionAlthough the clinical benefit of omalizumab in asthma and chronic spontaneous urticaria (CSU) has been established in several clinical trials, there are very little data about its effect on severe VKC. In addition to few previously reported cases we can report the rapid effectiveness of omalizumab in VKC clinically and in terms of quality of life. Randomized trials are needed to include omalizumab in third-line treatment of VKC for prevention of visual impairment and further sequelae such as corneal damage.

Outcomes to first-line pembrolizumab in patients with PD-L1-high (≥50%) non-small-cell lung cancer and a poor performance status.

9568 Background: Patients with non-small cell lung cancer (NSCLC) and a poor Eastern Cooperative Oncology Group performance status (ECOG PS) have been excluded from immunotherapy clinical trials. We sought to evaluate clinical outcomes to first-line pembrolizumab in patients with advanced NSCLC, a PD-L1 tumor proportion score (TPS) of ≥50%, and an ECOG PS of 2. Methods: We performed a multicenter retrospective analysis of patients with metastatic NSCLC and a PD-L1 tumor proportion score (TPS) of ≥50% (negative for genomic alterations in EGFR and ALK) who received treatment with first-line commercial pembrolizumab. Clinical outcomes were compared in patients based on ECOG PS. Results: Among 234 patients, 83.3% (N = 195) had an ECOG PS of 0 or 1, and 16.7% (N = 39) had an ECOG PS of 2. The baseline clinicopathological characteristics were balanced between the ECOG PS 0-1 vs 2 groups in terms of age, sex, tobacco use, histology, KRAS mutation status, presence of other potentially targetable driver mutations ( BRAF, MET, HER2, RET), history of central nervous system (CNS) disease, and PD-L1 TPS distribution. Compared to patients with an ECOG PS of 0-1, patients with an ECOG PS of 2 had a significantly lower objective response rate (ORR 43.1% vs 25.6%; P = 0.04), a numerically shorter median progression free survival (mPFS 6.6 months vs 4.0 months; P = 0.09), and a significantly shorter median overall survival (mOS 20.3 months vs 7.4 months; P < 0.001). Upon disease progression, patients with an ECOG PS of 2 were significantly less likely to receive second-line systemic therapy compared to patients with an ECOG PS of 0-1 (55.5% vs 14.3%, P < 0.001). Conclusions: Although a subset of patients with an ECOG PS of 2 can respond first-line pembrolizumab, clinical outcomes in this population are poor, and use of second-line systemic therapy is infrequent.

Multicenter analysis of treatment outcomes for well differentiated grade 3 neuroendocrine tumors (NET G3).

4607 Background: Well differentiated grade 3 neuroendocrine tumors (NET G3) have been distinguished from poorly differentiated neuroendocrine carcinomas (NEC) in the most current WHO classifications from 2017 and 2019. Retrospective data suggest that commonly applied first-line chemotherapy protocols with cisplatin or carboplatin in combination with etoposide (PE) are less effective in NET G3 than NEC. Therefore, current treatment guidelines suggest alternative first-line treatment protocols like temozolomide-based (TEM), streptozotocin-based (STZ) and FOLFOX which have only been studied in second-line so far. The aim of this multicenter analysis was to evaluate treatment outcomes for NET G3 with a focus on the efficacy of different first-line regimens. Methods: We performed retrospective analysis of all patients with NET G3 in the NEN databases of 3 German cancer centers. All histopathological findings were reviewed by the investigators in order to comply with the most current WHO classification. Results: A total of 131 patients could be identified. Median Ki67 was 30 %, primary tumors were located in the pancreas in 71 % of cases, 20 patients had a history of prior NET G1/G2 diagnosis. Median overall survival (OS) was 138.1 months with a median follow-up of 20.4 months. 125 patients received palliative first-line therapy: PE n = 34, FOLFOX n = 36, TEM (mostly temozolomide+capecitabine) n = 21, STZ n = 19, other (including targeted agents, somatostatin analogues, PRRT and multimodal combination approaches) n = 15. Overall response (ORR) and disease control rate was 35.3 % and 67.6 % for PE, 52.8 % and 80.6 % for FOLFOX, 28.6 % and 66.7 % for TEM, 47.4 % and 68.4 % for STZ, 20.0 % and 73.3 % for other respectively. Median progression-free survival for PE was 5.2 months. Compared to PE, PFS in the other treatment groups was 6.0 months for FOLFOX (p = 0.164), 12.0 months for TEM (p = 0.059), 5.7 months for STZ (p = 0.519), 14.1 months for other (p = 0.003). All non-PE patients combined showed a significantly prolonged PFS vs. PE (9.0 vs. 5.2 months; p = 0.011). 89 patients received second-line systemic therapy with a median PFS of 5.3 months. Conclusions: In this first multicenter analysis of different treatment strategies for NET G3, patients receiving upfront treatment with non-PE regimens had a significantly prolonged PFS. Of the single defined protocols, FOLFOX showed the highest ORR, and TEM the longest PFS. Further prospective evaluation of the optimal therapeutic strategy for this newly defined tumor entity is needed.

Choice of second-line systemic therapy in stage IV small cell lung cancer (SCLC) – A decision-making analysis amongst European lung cancer experts

ObjectivesStage IV small cell lung cancer (SCLC) is associated with short survival and progression after first-line systemic therapy frequently occurs within months. Although topotecan is approved for second-line treatment, its efficacy is limited, and treatment heterogeneity exists. Material and methodsThe decision-making patterns for second line treatment of 13 European medical oncologists with expertise in SCLC were analyzed. ResultsThe two criteria most relevant to decision-making were the performance status and the interval of recurrence since first-line treatment.With an interval of less than 3 months since the end of first-line chemotherapy, 62 % of the experts recommended cyclophosphamide, doxorubicin and vincristine (CAV) for fit patients and 54 % recommended topotecan for unfit patients. For an interval of more than 6 months, a clear consensus for a re-challenge with a platinum doublet was achieved (92 %). However, there was no consensus on the second-line therapy with an interval of 3–6 months since the end of first-line therapy. ConclusionReal world practice may differ from recommendations in general guidelines and cannot always be directly derived from trial results as other factor such as habits, patient’s preference, convenience or costs have to be factored in.

Eligibility for second-line therapy in patients with advanced hepatocellular carcinoma (aHCC): A BC Cancer population-based study.

491 Background: Evidence supporting second-line therapies has become available for aHCC, including regorafenib, cabozantinib, ramucirumab, and nivolumab. The optimal second-line treatment regimen is unknown, and there remains limited real-world data about the eligibility of patients for second-line therapies in aHCC. We aimed to characterize the real-world eligibility and use of second-line therapies post sorafenib. Methods: We identified all patients with aHCC who received ≥1 cycle of first-line sorafenib between January 1, 2014 and December 31, 2017 across 6 centers in British Columbia (BC), Canada. All patients were required to be Child-Pugh class A for initiation of sorafenib in BC. Baseline characteristics and clinical outcomes were reviewed. Eligibility for second-line therapy was determined using the RESORCE and CELESTIAL study entry criteria. Results: Of 144 patients with advanced HCC who received ≥1 cycle of first-line sorafenib, median age was 65.3 years (range 32.2-83.4) and 85% were male. Median duration of sorafenib was 2.6 months. 12 patients (8%) went on to receive second-line treatment. 37 patients (26%) were deemed eligible for second-line systemic therapy. Primary reasons for ineligibility included ECOG ≥2 (58%), and deterioration to Child-Pugh status B (28%). On Cox regression, improved survival was associated with better ECOG and recurrent disease. (Table). Kaplan-Meier analysis demonstrated that eligibility for second-line treatment was associated with improved median overall survival from end of first-line treatment (8.5 vs. 5.1 months; p<0.01). Conclusions: Only a minority of real-world patients with aHCC were eligible for second-line therapies based on second-line trial criteria. Given the high-rate of attrition, improved first-line treatment options are urgently needed. [Table: see text]

A retrospective study: Impact of consensus treatment plans on systemic therapy of pediatric morphea.

Morphea is an inflammatory and fibrosing condition that affects the skin and subcutaneous structures. Morphea is managed by dermatologists, rheumatologists, or both. Prior studies have suggested there is significant variability in approach to treatment. In 2012, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) published consensus treatment plans (CTPs) for pediatric morphea to develop more standardized treatment plans for patients requiring systemic therapy. We aimed to assess whether the publication of CTPs has impacted care of patients with morphea at our institution. Data were collected via a retrospective review of medical records of 61 pediatric patients diagnosed with morphea at Seattle Children's Hospital (SCH) from January 1, 2005, to December 12,2017. Prior to the publication of CTPs, 2 out of 24 patients (8.3%) were treated with a regimen that matched a subsequent CTP. After publication of CTPs, 29 out of 37 patients (78.4%) were treated with a regimen that matched a CTP (P<0.001). A subanalysis was performed to assess the number of patients who needed second- or third-line therapies. Of those who followed a CTP therapy plan (n=26), 3 patients (11.5%) needed a second-line therapy compared with 11 patients (44%) in the no-CTP followed group (n=25), (P=0.012). The publication of CTPs led to a significant change in treatment approach for patients with morphea requiring systemic therapy at SCH. Patients treated with one of the treatment plans recommended by the CTPs were less likely to need second-line systemic therapy.

Second-line therapies in advanced biliary tract cancers.

Biliary tract cancers constitute approximately 3% of gastrointestinal malignancies with poor prognosis. Surgical therapy is the main form of treatment in localised disease; however, for patients with advanced stage or unresectable disease, locoregional and systemic chemotherapeutics are primary treatment options. Although the combination of gemcitabine and cisplatin is a standard regimen of choice, there are no consensus guidelines that help in choosing an appropriate second-line therapy. Substantial progress has been made in the past decade to understand the tumorigenesis and genetic landscape of each biliary tract cancer subtype, which facilitates precision medicine for this cancer. Common genes implicated in biliary tract cancer tumorigenesis include IDH1, IDH2, FGFR1, FGFR2, FGFR3, EPHA2, BAP1, ARID1B, ELF3, PBRM1, PRKACA, PRKACB, HER2, and BRAF. With the advancements in molecular pathogenesis of biliary tract cancer, especially in an era of personalised medicine, many questions are yet to be answered in advanced stages of the cancer: what subset of patients might benefit from second-line drugs, how to choose an optimal second-line regimen, and their effects on quality of life. This Review seeks to summarise available literature and discuss the potential second-line systemic therapy options for advanced biliary tract cancer on the basis of advancements of our knowledge on molecular pathogenesis and tumorigenesis.

Investigation of the Efficacy and Safety of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma.

Nivolumab, an anti-PD-1 inhibitor, has demonstrated efficacy in patients with several types of recurrent and metastatic (R/M) squamous cell carcinoma of the head and neck. We evaluated patients with R/M-NPC receiving nivolumab. Twelve patients with R/M-NPC were enrolled at 4 institutions. The primary endpoint was overall survival, and secondary endpoints were i) progression-free survival (PFS), ii) overall response rate (ORR), iii) disease control rate (DCR), and iv) treatment-related toxicity. The 1-year survival rate was 75.8%, the median PFS was 2.8 months, and the 1-year PFS rate was 33.3%. The best therapeutic response was complete response in 2, stable disease in 3 and progressive disease in 7 patients. The ORR of all patients was 16.7% and the DCR was 41.7%. Nivolumab is a useful and relatively safe second-line systemic therapy in patients with R/M-NPC, and even patients who do not respond to nivolumab may survive for a long time.

Nivolumab-related severe thrombocytopenia in a patient with relapsed lung adenocarcinoma: a case report and review of the literature

BackgroundImmune checkpoint inhibitor therapy has changed the standard drug therapy for relapsed or advanced non-small cell lung cancer; its efficacy is well-recognized by pulmonary physicians, oncologists, and thoracic surgeons. Nivolumab, one of the anti-programmed cell death 1 antibodies, was the first immune checkpoint inhibitor to be approved and is used as a standard second-line regimen for patients with non-small cell lung cancer irrespective of the expression of programmed cell death ligand 1. Programmed cell death 1 antibodies have been generally confirmed to be less toxic than conventional cytotoxic chemotherapy, although unusual immune-related adverse events such as type I diabetes mellitus, adrenal failure, and myasthenia gravis may occur with a very low incidence. A case of severe grade V immune-related thrombocytopenia after two courses of nivolumab as second-line therapy for relapsed non-small cell lung cancer is reported.Case presentationAn 82-year-old Japanese woman with relapsed lung adenocarcinoma was treated with nivolumab as second-line systemic therapy at our institute. Her laboratory data indicated thrombocytopenia suspected to be an immune-related adverse event following two courses of nivolumab. Subsequently, she developed a massive pulmonary hemorrhage and left cerebral infarction despite intensive treatment including systemic steroid therapy. Although there have been a few reports of thrombocytopenia caused by nivolumab, this is the first report of grade V thrombocytopenia following administration of nivolumab for relapsed non-small cell lung cancer.ConclusionA very difficult case of grade V immune-related thrombocytopenia after the administration of nivolumab as second-line therapy for relapsed lung adenocarcinoma was described. Immune-related thrombocytopenia is a rare adverse event, but it must be considered a possible complication because it may become critical once it has occurred.

Incidence of Skeletal-Related Events in Patients with Castration-Resistant Prostate Cancer: An Observational Retrospective Cohort Study in the US.

Background and Objective Skeletal-related events (SREs) are common in men with bone metastases and have negative consequences for patients with castration-resistant prostate cancer (CRPC), including pain, reduced quality of life, and increased mortality. We estimated incidence rates of first SREs in a cohort of men with CRPC in the Surveillance, Epidemiology, and End Results-Medicare database. Methods We included men aged ≥ 65 years with a prostate cancer diagnosis in 2000-2011 if they had no prior malignancy (other than nonmelanoma skin cancer) and had surgical or medical castration with subsequent second-line systemic therapy, which was used to infer castration resistance. The first occurrence of an SRE (fracture, bone surgery, radiation therapy, or spinal cord compression) in Medicare claims was identified. Incidence rates of SREs were estimated in all eligible person-time and, in secondary analyses, stratified by any use of bone-targeted agents (BTAs) and history of SRE. Results Of 2,234 men with CRPC (84% white, mean age = 76.6 years), 896 (40%) had an SRE during follow-up, with 74% occurring within a year after cohort entry. Overall, the incidence rate of SREs was 3.78 (95% CI, 3.53-4.03) per 100 person-months. The incidence rate of SREs before any BTA use was 4.16 (95% CI, 3.71-4.65) per 100 person-months, and after any BTA use was 3.60 (95% CI, 3.32-3.91) per 100 person-months. The incidence rate in patients with no history of SRE was 3.33 (95% CI 3.01-3.68) per 100 person-months, and in patients who had such a history, it was 4.20 (95% CI 3.84-4.58) per 100 person-months. Conclusions In this large cohort of elderly men with CRPC in the US, SREs were common. A decrease in incidence of SREs after starting BTA is suggested, but the magnitude of the effect may be confounded by indication and other factors such as age and prior SRE.

Abstract CT086: Interim results from CLASSICAL-Lung, a Phase Ib/II study of VX15/2503 (pepinemab) in combination with avelumab in advanced NSCLC

Abstract Background: Blockade of the PD/PD-L1 pathway is an effective immunotherapy for NSCLC, however rational combination therapies are needed to overcome resistance mechanisms. VX15/2503 (pepinemab) is an IgG4 humanized monoclonal antibody targeting semaphorin 4D (SEMA4D, CD100). In vivo preclinical models demonstrated antibody blockade of SEMA4D promoted immune infiltration and reduced function and recruitment of immunosuppressive myeloid cells within the tumor. Importantly, preclinical combinations of anti-SEMA4D with various immunotherapies enhanced T cell activity and tumor regression. Avelumab is a fully human IgG1 antibody specific for PD-L1 and has been approved for both Merkel cell and urothelial carcinomas. The CLASSICAL-Lung clinical trial tests the combination of pepinemab with avelumab to couple immune activation via checkpoint inhibition with beneficial modifications of the immune microenvironment via pepinemab. Here, we present interim results of the dose escalation portion of the CLASSICAL-Lung study. Methods: This Phase Ib/II, open label, single arm, first-in-human combination study is designed to evaluate the safety, tolerability and efficacy of pepinemab in combination with avelumab in 62 subjects with advanced (IIIB/IV) NSCLC. The trial is split into dose escalation (n=12) and dose expansion (n=50) phases. The dose escalation portion includes patients who are immunotherapy naïve and have either progressed or declined standard first or second-line systemic anticancer therapy. The expansion phase includes a similar patient cohort as well as a second cohort of patients whose tumors progressed during or following immunotherapy. Patients in the dose escalation cohorts received ascending doses of pepinemab (5, 10, 20 mg/kg, Q2W) in combination with avelumab (10mg/kg, Q2W). The primary objective of dose escalation is safety, tolerability, and identification of the RP2D for dose expansion. Secondary objectives include evaluation of efficacy, immunogenicity, and PK/PD, and an exploratory objective is to identify candidate biomarkers of activity. Results / Conclusions: Dose escalation was successfully completed. The combination was found to be well tolerated at all dose levels tested and the RP2D was selected as 10mg/kg pepinemab Q2W (with 10mg/kg avelumab Q2W) for the dose expansion phase. No concerning safety signals have been identified to date. The most frequent related AEs were grades 1 or 2 fatigue, pyrexia, or chills; no grade 3 AE occurred in more than one subject. One DLT, a grade 3 pulmonary embolism occurred in the 10mg/kg pepinemab cohort, resolved and did not recur in that same subject or additional subjects in any cohort. The disease control rate to date in all dose escalation patients treated for at least two months is 90%. More detailed data from the dose escalation cohorts will be presented, as well as an enrollment update for the dose expansion phase. Clinical trial information: NCT03268057 Citation Format: Michael Shafique, Terrence L. Fisher, Elizabeth E. Evans, John E. Leonard, Desa Rae Pastore, Crystal Mallow, Ernest Smith, Maurice Zauderer, Andreas Schröeder, Kevin Chin, Thaddeus Beck, Megan Baumgart, Rachel E. Sanborn, Jonathan W. Goldman. Interim results from CLASSICAL-Lung, a Phase Ib/II study of VX15/2503 (pepinemab) in combination with avelumab in advanced NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT086.

Incidence of Second Primary Malignancies in Patients with Castration-Resistant Prostate Cancer: An Observational Retrospective Cohort Study in the United States.

Background New therapies for castration-resistant prostate cancer (CRPC) may be associated with increased risk of second primary malignancies (SPM). We therefore estimated the population-based incidence of SPM among patients with CRPC in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. We also estimated the proportion of men with CRPC with bone metastases and overall survival. Methods We conducted a retrospective cohort study of United States (US) men aged ≥ 65 years with CRPC. Cohort entry was from January 1, 2000, to December 31, 2011, with follow-up through December 31, 2013. Castration resistance was defined by treatment with second-line systemic therapy (after surgical or medical castration). SPM were diagnoses of primary cancers (other than prostate) in SEER or Medicare data. Results Altogether 2,234 patients met eligibility criteria. Most (1,887; 84.5%) had evidence of bone metastases in Medicare claims. SPM occurred in 172 patients (incidence rate 5.9 per 100 person-years; 95% confidence interval [CI], 5.0-6.8; standardized incidence ratio = 3.1, 95% CI, 2.8-3.6, based on SEER incidence rate of all malignancies except prostate cancer among men aged ≥ 65 years). The most common SPM were lung/bronchus (n = 29, 16.9%), urinary bladder (n = 22, 12.8%), and colon/rectum (n = 21, 12.2%). Median survival was 1.2 years (95% CI, 1.1-1.3); 5-year survival was 9% (95% CI, 7-11%). Conclusions This study provides the first estimate of SPM risk in older men with CRPC in the US. The incidence rate is approximately threefold higher than the population-based cancer incidence among men without prostate cancer.

Clinical Outcomes of 42 Renal Cell Carcinoma Patients With Metastases Solely to the Lung Who Received Sorafenib as Second-line Systemic Therapy

In renal cell carcinoma (RCC), sorafenib was the first targeted agent demonstrating a definitive benefit in a large phase III clinical trial. The objective of this study was to assess the clinical outcomes of 42 consecutive RCC patients with metastases solely to the lung who received sorafenib as a second-line systemic agent. Of the 42 patients, 14 (33.3%) and 28 (66.7%) received cytokine therapy and sunitinib, respectively, prior to treatment with sorafenib. In this series, all patients initially received 400 mg of sorafenib twice daily on a continuous dosing schedule. The efficacy and safety of second-line sorafenib in these 42 patients were retrospectively evaluated. As the best response to sorafenib, 2 (4.8%), 14 (33.3%), 22 (52.4%) and 4 (9.5%) patients were judged to show a complete response, partial response, stable disease and progressive disease, respectively. The median progression-free survival (PFS) and overall survival (OS) after the introduction of sorafenib was 10.6 and 30.2 months, respectively. Multivariate analyses of several parameters identified the following independent prognostic predictors: C-reactive protein (CRP) level for PFS, and International Renal Cell Carcinoma Database Consortium classification and CRP level for OS. The common adverse events associated with sorafenib were hand-foot syndrome, hypertension and diarrhea, which developed in 22 (52.4%), 17 (40.5%) and 13 (31.0%), respectively; however, any AEs corresponding to ≥grade 3 occurred in only 16 (38.1%). Favorable disease control with acceptable tolerability might be expected by introducing sorafenib as second-line therapy for RCC patients with metastases solely to the lung; therefore, sorafenib could be the optimal option for this category of patients.

Platinum rechallenge in second-line treatment for endometrial carcinoma

Objectives: Metastatic endometrial carcinoma (EC) has a poor prognosis. Systemic treatment (hormone therapy or chemotherapy) has been used in first line, however, the best therapy as second-line therapy is not known. The aim of this study is to evaluate the role of platinum-based chemotherapy rechallenge in second-line treatment for EC. Materials and Methods: Retrospective review of patients with recurrent EC who were treated with second-line systemic therapy from April 2007 to April 2015 at two cancer centers. Clinical data included: age, histology, tumor grade, tumor stage at diagnosis, site of disease progression, ECOG performance status, adjuvant chemotherapy, first-and second-line chemotherapy for recurrent disease and comorbidities. Results: A total of 84 patients were evaluated. Median age was 66.2 years; most patients had endometrioid histology (67.9%) and grade 2 tumors (45.8%). Twenty-nine patients (34.5%) were treated with platinum rechallenge at second line. Median overall survival (OS) was 9.7 months (7.1-12.3 months; 95% CI). Longer OS was observed in platinum rechallenge group compared to non-re-exposed (13.8 months vs. 7.9 months, p = 0.005). Only platinum rechallenge was significantly associated to a better OS on multivariate analysis (HR 0.43 [95%CI 0.21-0.87, p = 0.019]). Platinum rechallenge was also associated with a higher progression-free survival (PFS) (4.9 months vs. 3.4 months, p = 0.008). Conclusions: The present findings suggest a longer OS and PFS for patients treated with platinum rechallenge at second-line treatment for EC and add more evidence for adoption of this strategy in a scenario where there is little evidence of effective treatments.

Treatment Outcomes and Sensitivity to Hormone Therapy of Aggressive Angiomyxoma: A Multicenter, International, Retrospective Study.

Aggressive angiomyxoma (AA) is a rare, locally aggressive tumor usually arising from pelvis or perineum, with a high local-recurrence rate after complete surgery. Anecdotal responses to hormone therapy have been reported. In the present study we aimed at studying surgical treatment outcomes and sensitivity to hormone therapy of AA. We conducted a multicenter, international retrospective effort including patients with AA treated at three European referral centers (Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy and the Italian Rare Cancer Network; Centre Léon Bérard, Lyon, France; and Hospital Universitario Virgen del Rocio, Seville, Spain). A total of 36 patients were included. Median follow-up was 51.3 months. Thirty-three patients (92%) underwent complete (R0 + R1) surgery, with a local relapse rate of 50% and a median relapse-free survival of 39 months (95% confidence interval [CI], 27-68.1). Thirteen patients received a first-line systemic treatment with hormone therapy for locally advanced disease, with an overall response rate of 62% and a median progression-free survival of 24.6 months (95% CI, 11.0-39.7). In two patients, adding an aromatase inhibitor (AI) on progression to first-line GnRH agonist (GnRHa) resulted in a new tumor response. Our findings confirm that in AA, surgical local control may be challenging, with a significant rate of local relapse despite complete surgery. Hormone therapy is an active treatment option, with a potential of disease control and of being combined with surgery. The addition of an AI to first-line GnRHa could be an effective second-line systemic therapy in premenopausal female patients with AA. In this retrospective effort including 36 patients with aggressive angiomyxoma, local relapse rate after complete surgery was 50%, with a median relapse-free survival of 39 months, confirming that local control is challenging. Overall response rate to first-line hormone therapy was 62%, with a median progression-free survival of 24.6 months. Thus, hormone therapy has a potential of disease control and of being combined with surgery.

CURRENTLY AVAILABLE TREATMENT OPTIONS FOR METASTATIC RENAL CELL CARCINOMA

Over the last 10 years, the capacities of second-line systemic therapy for metastatic renal cell carcinoma (mRCC) changed significantly. Targeted therapy is a standard treatment for patients with mRCC. However, the choice of therapeutic agents for such patients remains challenging. In the absence of reliable prognostic biomarkers, physicians can use only the results of randomized clinical trials and their own routine experience with targeted drugs when choosing a regimen of second-line therapy. The article discusses the current situation with second-line therapy with the three new options available for patients with mRCC. It also contains a case report, describing our successful experience of treatment a female patient that received 6 variants of chemotherapy with good effect during 89 months after the diagnosis.

PCN264 - ASSESSMENT OF TREATMENTS AND HEALTH CARE UTILISATION (HCU) IN SPAIN FOLLOWING INITIAL PLATINUM THERAPY FOR RECURRENT OR METASTATIC (R/M) HEAD AND NECK SQUAMOUS CELL CARCINOMA (HNSCC)

To assess treatment patterns and HCU among patients with R/M HNSCC in Spain who experienced progression during or after platinum-based chemotherapy. Physicians in Spain recruited by convenience sampling reviewed medical records of adult patients who experienced disease progression between 1 January 2011 and 31 March 2016. Progression must have occurred during or after palliative platinum chemotherapy for R/M HNSCC or within 6 months after platinum chemotherapy as part of a multimodality therapy with curative intent. Disease characteristics, treatment patterns, and HCU (including drug administration encounters) were described. Data for 196 patients (median age 58.6 years) were extracted by 43 physicians. Second-line systemic therapy was received by 154 (78.6 %) patients; 42 (21.4%) patients received best supportive care only. The most frequently received second-line regimens were cetuximab+paclitaxel (n=38, 24.7%), paclitaxel monotherapy (n=19, 12.3%), and single-agent cetuximab (n=18, 11.7%). Of patients receiving second-line treatment, only 38 (24.7%) received third-line treatment. During second-line treatment, hospital outpatient and community health visits were reported for 64 (41.6%) and 24 (15.6%) patients (median 0.9 and 0.7 visits/month, respectively); 33 (21.4%) patients required emergency department visits, and treatment- or procedure-related complications (n=15, 45.5%) were the most common reason for these visits. Hospitalisations during second-line treatment were reported for 35 (22.7%) patients; median length of stay was 10 days. Palliative care (n=18, 51.4%), disease progression (n=17, 48.6%), and treatment- or procedure-related complications (n=8, 22.9%) were common reasons for hospitalization. After progression on initial platinum therapy, 21.4% patients received best supportive care and, of the 154 (78.6%) receiving second-line therapy, only 24.7% received subsequent treatments. A considerable proportion of patients were hospitalised for disease- and treatment-related issues, highlighting the need for improved safety of new treatments.

Prognostic significance of pre-treatment neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with glioblastoma.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumour in adults. Identification of accessible and cost-effective prognostic factors may better guide adjuvant treatment-related decisions. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of host inflammatory response, and their increase has recently been shown to be a poor prognostic factor in several malignancies. The aim of the present study was to investigate the prognostic value of preoperative NLR and PLR in GBM patients. Between 2012 and 2017, 104 patients who had undergone surgery for GBM were considered for adjuvant therapy in our institution. Of those, 80 patients with evaluable pre-corticosteroid full blood count results were identified and included in the final analysis. The Eastern Cooperative Oncology Group performance status, localization, radiochemotherapy and second-line systemic therapy were found to be independent prognostic indicators for progression-free and overall survival. The median overall survival was 13.2 months. Patients with NLR <4 had a better median overall survival of 10.7 vs. 7.8 months in patients with NLR >4; however, this difference was not statistically significant (P>0.05). Overall survival also did not differ significantly between patients with low and those with high PLR values (10.2 vs. 15.2 months, respectively; P=0.105). In conclusion, the results of the present study suggest that pre-treatment NLR and PLR do not have prognostic value in GBM patients; however, large-scale trials are required to confirm these findings.