Third-line Treatment For Patients Research Articles

Etirinotecan Pegol (NKTR-102) in Third-line Treatment of Patients With Metastatic or Recurrent Non–Small-cell Lung Cancer: Results of a Phase II Study

BackgroundThird-line treatment options are limited for patients with metastatic non–small-cell lung cancer (NSCLC). Etirinotecan pegol (NKTR-102) is a long-acting topoisomerase-I inhibitor. We conducted a single-arm phase II trial to evaluate its efficacy in third-line treatment. Patients and MethodsPatients aged ≥ 18 years with histologically proven NSCLC who had received 2 previous systemic therapy regimens, measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1, and adequate end-organ function were eligible. Etirinotecan pegol was administered at a dose of 145 mg/m2 intravenously once every 3 weeks until progression. The response was assessed every 6 weeks using Response Evaluation Criteria In Solid Tumors, version 1.1. The primary endpoint was the overall objective response rate. The secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. A Simon 2-stage design was implemented for futility. ResultsFrom January 2013 to January 2015, 40 patients were enrolled. Their median age was 66 years (range, 19-85 years), 45% were female, 30% had an ECOG performance status of 0, 96% were current and former smokers, and 31 had adenocarcinoma. Patients received a median of 3 cycles (range, 2-15) of protocol therapy. The best response was a partial response in 2 patients. The treatment was well tolerated; 3 patients had grade 3 gastrointestinal toxicity attributable to therapy. The median PFS was 2.3 months (95% confidence interval [CI], 1.3-4.4 months), and the median OS was 7.1 months (95% CI 4.2-11.4 months). ConclusionsEtirinotecan pegol was well tolerated and led to 2 partial responses and disease stabilization with this third-line treatment of metastatic NSCLC. However, the study failed to meet its prespecified response rate endpoint.

Redefining Later-Line Therapy in Metastatic Colorectal Cancer

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the fourth leading cause of cancer death in the world, accounting for approximately 1.4 million new cases and almost 700,000 deaths in 2012.1 The objective of the symposium was to provide an overview of the current treatment landscape in terms of later-line therapy in metastatic CRC (mCRC) and to discuss the evidence for the various options available, including rechallenge and therapies such as trifluridine (FTD)/tipiracil (TPI) (Lonsurf®; also known as TAS-102) and regorafenib (Stivarga®). The symposium started by examining the clinical value of third-line treatment in patients with mCRC and providing an insight into the mechanism of action of FTD/TPI, and a comparison with that of 5-fluorouracil (5-FU). The safety and efficacy of FTD/ TPI was then discussed together with the practical management of patients on treatment. The speakers tackled the issue of rechallenge and reintroduction as an option in the third-line, reviewing the pros and cons, and the available studies providing information on the safety and efficacy of the different options in later lines, concluding that there is a lack of robust evidence for rechallenge as a clinical decision. This was followed by a review of the compelling evidence for the use of treatments such as FTD/TPI and regorafenib in the third-line, with documented evidence for efficacy.

Phase II study of paclitaxel associated with lipid core nanoparticles (LDE) as third-line treatment of patients with epithelial ovarian carcinoma

Ovarian cancer is often diagnosed at advanced stages, when poorly responsive to standard treatment. First-line treatment consists in schemes including cytoreductive surgery followed by adjuvant chemotherapy schemes with platinum and taxane derivatives. Second-line regimens are based on gemcitabine and liposomal doxorubicin. Third line is often not worthwhile because of the high toxicity with poor response to treatment. Previously, we showed that paclitaxel (PTX) carried in non-protein lipid core nanoparticles (LDE) resembling the chemical structure of LDL has remarkably reduced toxicity. Here, the hypothesis was tested whether PTX-LDE could safely benefit patients in third-line treatment setting. Fourteen women unresponsive to second-line chemotherapy for ovarian cancer, aged 61±10years, clinical stage IV and TqNqM1, were included. PTX-LDE was administered at 175mg/m2, 3/3week dose. Patients were submitted to clinical examinations before each chemotherapy cycle. Serum biochemistry and imaging examinations to monitor disease progression were performed. In total, 74 cycles of chemotherapy were done and, in all cycles, clinical or laboratorial toxicities were not observed. Median progression-free survival (PFS) was 3.0months (95% CI 2.0-3.9). In four patients, PFS was >6months and in 2>1year. The unpreceded, striking absence of toxicity and consistently long PFS, compared to previous results, indicate that at least 4 among 14 patients had tumor arrest by the treatment and clear benefit of PTX-LDE at third-line setting. The absence of observable toxicity allows dose escalating to improve response to treatment, as perspective to be tested in the ensuing studies.

A randomized phase II study of paclitaxel alone versus paclitaxel plus sorafenib in second- and third-line treatment of patients with HER2-negative metastatic breast cancer (PASO)

BackgroundWe conducted an open-label, randomized, two-arm multi-center study to assess the efficacy and safety of paclitaxel versus paclitaxel + sorafenib in patients with locally advanced or metastatic HER2-negative breast cancer.MethodsPatients were randomly assigned to receive either paclitaxel monotherapy (80 mg/m2) weekly (3 weeks on, 1 week off) plus sorafenib 400 mg orally, twice a day taken continuously throughout 28 day cycles. Sorafenib dose was gradually escalated from a starting dose of 200 mg twice a day. The primary endpoint was progression free survival (PFS).ResultsA pre-planned efficacy interim analysis was performed on the data of 60 patients, 30 patients in each treatment arm. Median PFS was estimated at 6.6 months (95% CI: 5.1 to 9.0) in patients randomized to single-agent paclitaxel (Arm A) and 5.6 months (95% CI: 3.8 to 6.5) in patients randomized to paclitaxel-sorafenib combination (Arm B) therapy. Contrary to the hypothesis, the treatment effect was statistically significant in favor of paclitaxel monotherapy (hazard ratio 1.80, 95% CI: 1.02 to 3.20; log-rank test P = 0.0409). It was decided to stop the trial early for futility. Median OS was also in favor of Arm A (20.7 months (95% CI: 16.4 to 26.7) versus 12.1 months (95% CI: 5.8 to 20.4) in Arm B. Clinical control was achieved in 28 patients (93.3%) in Arm A and in 21 patients 70.0% in Arm B. Overall response rate was met in 43.3% of patients in Arm A and in 40.0% in Arm B. Toxicities were increased in Arm B with higher rates of diarrhea, nausea, neutropenia, hand-foot skin reaction (HFSR) and anorexia, Grad 3 and 4 toxicities were rare.ConclusionsIn this pre-planned interim analysis, paclitaxel-sorafenib combination therapy was not found to be superior to paclitaxel monotherapy with regard to the primary end point, progression-free survival. The trial was therefore discontinued early. There was no indication of more favorable outcomes for combination therapy in secondary efficacy end points. As expected, the safety and toxicity profile of the combination therapy was less favorable compared to monotherapy. Overall, this trial did not demonstrate that adding sorafenib to second- or third-line paclitaxel provides any clinical benefit to patients with HER2-negative advanced or metastatic breast cancer. Cautious dosing using a sorafenib ramp up schedule might have contributed to negative results.Trial registrationThe study was registered at EudraCT (No 2009–018025-73) and retrospectively registered at Clinical trials.gov on March 17, 2011 (NCT01320111).

Apatinib plus icotinib in treating advanced non-small-cell lung cancer after icotinib treatment failure.

e20528 Background: Icotinib, a small-molecule EGFR TKI, has been approved as the first-line therapy for treating advanced non-small-cell lung cancer (NSCLC) in China. However, treatment failures frequently occurred in NSCLC patients with EGFR-sensitizing mutations. A phase II clinical trial has reported the beneficial survival of apatinib, a new small-molecular VEGFR TKI, in treating NSCLC (Zhang et al. 2012 ASCO, 7548). This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib as second- or third-line treatment in patients with advanced NSCLC. Methods: This study comprised 27 patients diagnosed with advanced NSCLC and treated with icotinib and apatinib as the second- or third-line therapy. Patients received oral icotinib (125 mg, tid), alone initially. When disease progressed, they received icotinib plus apatinib (500 mg, qd, orally). Treatment was continued until disease progression or unacceptable toxic effects. Efficacy was evaluated based on RECIST version 1.0 and toxic effects were assessed using the NCI-CTC version 2.0. Results: Followed up to December, 2016, the median time of apatinib treatment was 7.47 months, and 8 of 27 patients were dead. The median overall survival had not reached and the median progression-free survival (PFS) was 5.33 months (95% CI 3.63-7.03 months). Moreover, the objective response rate (ORR) was 11.1% and the disease control rate (DCR) was 81.5%. Fourteen patients received icotinib and apatinib as the second-line treatment, and the RR and DCR were 7.1% and 78.6%. The remaining 13 patients received drugs as the third-line treatment, with an ORR and a DCR of 15.4% and 84.6%. Additionally, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months (95% CI 4.17-8.57 months) and 16 patients experienced icotinib monotherapy failure after 6 months with median PFS of 2.60 months (95% CI 0.00-8.54 months). The common drug-related toxic effects included hypertension (44.4%), fatigue (37.0%) and hand-foot syndromes (18.5%). Conclusions: Apatinib plus icotinib is efficacious in treating patients with advanced NSCLC after icotinib treatment failure, with acceptable toxic effects.

Real-world treatment patterns for patients receiving second-line and third-line treatment for advanced non-small cell lung cancer: A systematic review of recently published studies

Most patients with advanced non-small cell lung cancer (NSCLC) have a poor prognosis and receive limited benefit from conventional treatments, especially in later lines of therapy. In recent years, several novel therapies have been approved for second- and third-line treatment of advanced NSCLC. In light of these approvals, it is valuable to understand the uptake of these new treatments in routine clinical practice and their impact on patient care. A systematic literature search was conducted in multiple scientific databases to identify observational cohort studies published between January 2010 and March 2017 that described second- or third-line treatment patterns and clinical outcomes in patients with advanced NSCLC. A qualitative data synthesis was performed because a meta-analysis was not possible due to the heterogeneity of the study populations. A total of 12 different study cohorts in 15 articles were identified. In these cohorts, single-agent chemotherapy was the most commonly administered treatment in both the second- and third-line settings. In the 5 studies that described survival from the time of second-line treatment initiation, median overall survival ranged from 4.6 months (95% CI, 3.8–5.7) to 12.8 months (95% CI, 10.7–14.5). There was limited information on the use of biomarker-directed therapy in these patient populations. This systematic literature review offers insights into the adoption of novel therapies into routine clinical practice for second- and third-line treatment of patients with advanced NSCLC. This information provides a valuable real-world context for the impact of recently approved treatments for advanced NSCLC.

Efficacy and safety of eribulin as first- to third-line treatment in patients with advanced or metastatic breast cancer previously treated with anthracyclines and taxanes

ObjectivesDespite the survival benefit and acceptable tolerability of eribulin for advanced/metastatic breast cancer (MBC) patients pretreated with anthracyclines and taxanes, there is limited evidence of the clinical benefit of early eribulin use. We investigated the efficacy and safety of first- to third-line eribulin use in patients with MBC. Materials and methodsIn this phase II, open-label, single-arm study conducted at 14 sites in Kyushu, Japan, women with histologically confirmed human epidermal growth factor receptor 2–negative MBC were enrolled between December 1, 2011 and November 30, 2013 (Data cut-off: November 30, 2014). Objective response rate (ORR; primary endpoint), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and safety were evaluated. ResultsOf 53 recruited patients, 47 were enrolled. The ORR was 17.0% (95% confidence interval, 7.6–30.8), DCR was 66.0% (51.2–77.8), median PFS was 4.9 months (3.5–7.0), DOR was 6.6 months (1.9–14.3), and median OS was 17.4 months (10.1–not evaluable). The common grade 3/4 adverse events were neutropenia (25 patients; 53.2%), leucopenia (16 patients; 42.1%) and febrile neutropenia (4 patients; 8.5%). Toxicity did not increase during the long-term treatment. Subgroup analysis indicated that first-line treatment led to higher ORR and prolonged PFS and OS than second-/third-line treatment and that incidence of adverse events in patients of second-/third-line treatment was not higher than that in patients of first-line treatment. ConclusionEribulin exhibited efficacy and manageable tolerability in Japanese women with pretreated MBC in first- to third-line use. (ID: UMIN000007121).

Treatment of chronic spontaneous urticaria with an inadequate response to H1-antihistamines: an expert opinion.

Chronic spontaneous urticaria (CSU) is characterized by the sudden, continuous or intermittent appearance of pruritic wheals (hives), angioedema, or both for six weeks or more, with no known specific trigger. The international EAACI/GA2LEN/EDF/WAO urticaria guideline advises standard-dose, second-generation H1-antihistamines as first-line therapy. However, H1-antihistamine treatment leads to absence of symptoms in fewer than 50% of patients. Updosing of second-generation H1-antihistamines (up to fourfold) as recommended by the EAACI/GA2LEN/EDF/WAO urticaria guideline as second-line therapy, can improve response, but many patients remain symptomatic. Definitions of response are often subjective and a consensus is needed regarding appropriate treatment targets. There is also an unmet need for biomarkers to assess CSU severity and activity and to predict treatment response. The EAACI/GA2LEN/EDF/WAO urticaria guideline recommends add-on omalizumab, ciclosporin A (CsA), or montelukast third-line treatment in patients with an inadequate response to high-dose H1-antihistamines. Omalizumab is currently the only licensed systemic biologic for use in CSU. Both omalizumab and CsA are effective third-line CSU treatments; montelukast appears to have lower efficacy in this setting. Omalizumab carries a label warning for anaphylaxis, although no cases of anaphylaxis were reported in the phase III trials of omalizumab in CSU and it is generally well tolerated in patients with CSU. Omalizumab arguably has a better safety profile than CsA.

Evaluation of Efficacy and Safety of Ponatinib as Third-line Treatment in Patients with the Diagnosis of Chronic Phase Chronic Myeloid Leukemia

Evaluation of Efficacy and Safety of Ponatinib as Third-line Treatment in Patients with the Diagnosis of Chronic Phase Chronic Myeloid Leukemia

Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial

There are no systemic treatments for patients with hepatocellular carcinoma (HCC) whose disease progresses during sorafenib treatment. We aimed to assess the efficacy and safety of regorafenib in patients with HCC who have progressed during sorafenib treatment. In this randomised, double-blind, parallel-group, phase 3 trial done at 152 sites in 21 countries, adults with HCC who tolerated sorafenib (≥400 mg/day for ≥20 of last 28 days of treatment), progressed on sorafenib, and had Child-Pugh A liver function were enrolled. Participants were randomly assigned (2:1) by a computer-generated randomisation list and interactive voice response system and stratified by geographical region, Eastern Cooperative Oncology Group performance status, macrovascular invasion, extrahepatic disease, and α-fetoprotein level to best supportive care plus oral regorafenib 160 mg or placebo once daily during weeks 1-3 of each 4-week cycle. Investigators, patients, and the funder were masked to treatment assignment. The primary endpoint was overall survival (defined as time from randomisation to death due to any cause) and analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01774344. Between May 14, 2013, and Dec 31, 2015, 843 patients were screened, of whom 573 were enrolled and randomised (379 to regorafenib and 194 to placebo; population for efficacy analyses), and 567 initiated treatment (374 received regorafenib and 193 received placebo; population for safety analyses). Regorafenib improved overall survival with a hazard ratio of 0·63 (95% CI 0·50-0·79; one-sided p<0·0001); median survival was 10·6 months (95% CI 9·1-12·1) for regorafenib versus 7·8 months (6·3-8·8) for placebo. Adverse events were reported in all regorafenib recipients (374 [100%] of 374) and 179 (93%) of 193 placebo recipients. The most common clinically relevant grade 3 or 4 treatment-emergent events were hypertension (57 patients [15%] in the regorafenib group vs nine patients [5%] in the placebo group), hand-foot skin reaction (47 patients [13%] vs one [1%]), fatigue (34 patients [9%] vs nine patients [5%]), and diarrhoea (12 patients [3%] vs no patients). Of the 88 deaths (grade 5 adverse events) reported during the study (50 patients [13%] assigned to regorafenib and 38 [20%] assigned to placebo), seven (2%) were considered by the investigator to be related to study drug in the regorafenib group and two (1%) in the placebo group, including two patients (1%) with hepatic failure in the placebo group. Regorafenib is the only systemic treatment shown to provide survival benefit in HCC patients progressing on sorafenib treatment. Future trials should explore combinations of regorafenib with other systemic agents and third-line treatments for patients who fail or who do not tolerate the sequence of sorafenib and regorafenib. Bayer.

Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial

SummaryBackgroundErlotinib is approved for the treatment of all patients with advanced non-small cell lung cancer (NSCLC), but is most active in the treatment of EGFR mutant NSCLC. Cabozantinib, a small molecule tyrosine kinase inhibitor, targets MET, VEGFR, RET, ROS1, and AXL, which are implicated in lung cancer tumorigenesis. We tested the efficacy of cabozantinib and the combination of erlotinib plus cabozantinib, as compared with erlotinib, in patients with EGFR wild-type NSCLC.MethodsIn this three arm, randomised phase 2 study, the primary endpoint was to compare progression-free survival (PFS) of patients treated with cabozantinib versus erlotinib alone, and the combination of erlotinib plus cabozantinib versus erlotinib alone. Patients were eligible if they had received 1–2 previous treatments for advanced non-squamous EGFR wild-type NSCLC. Patients were stratified by performance status and line of therapy, then randomised using permuted blocks within strata to receive open label oral daily dosing of erlotinib (150 mg), cabozantinib (60 mg), or erlotinib (150 mg) and cabozantinib (40 mg). Imaging was performed every 8 weeks. At the time of radiographic progression, there was optional crossover for patients in either single agent arm to receive combination therapy. The comparison between erlotinib and each of the arms was powered (91%) to detect a PFS hazard ratio (HR) of 0.5 (1-sided p-value 0.10-level). Secondary objectives were overall survival (OS), radiographic response by RECIST version 1.1 and description of adverse events by CTCAE version 4.0. This trial is registered with ClinicalTrials.gov, number NCT01708954.FindingsAt complete enrollment, we randomised 125 patients (42 assigned to erlotinib, 40 assigned to cabozantinib, 43 assigned to the combination), of which 111 (89%) were eligible and received treatment per protocol were included in the primary analysis (38, 38, and 35 patients on erlotinib, cabozantinib, and combination, respectively). Compared to erlotinib alone (median 1.8 months), PFS was significantly improved in the cabozantinib arm (4.3 months, HR 0.39, 1-sided p=0.0003, 80% CI 0.27–0.55) and also in the erlotinib plus cabozantinib arm (4.7 months, HR 0.37, 1-sided p=0.0003, 80% CI 0.25–0.53).The safety analysis population included all patients who received study therapy regardless of eligibility. The most common grade 3 or 4 adverse events were diarrhea (3 [8%] in the erlotinib group vs 3 [8%] in the cabozantinib group vs 11 [28%] in the erlotinib and cabozantinib group), hypertension (none vs 10 [25%] vs 1 [3%]), fatigue (5 [13%] vs 6 [15%] vs 6 [15%]), oral mucositis (none vs 4 [10%] vs 1 [3%]), and thromboembolic event (none vs 3 [8%] vs 2 [5%]). Adverse events that were grade 3 or worse occurred in 13 (33%) patients in the erlotinib group, in 28 (70%) patients in the cabozantinib group, and in 28 (72%) patients in the erlotinib and cabozantinib group. One death of respiratory failure occurred in the cabozantinib group, deemed possibly related to either drug or disease, and one death occurred in the erlotinib plus cabozantinib group from pneumonitis. MET IHC results were available on 86 patients from the primary analysis and 85% were scored as positive (1–3+ membrane or cytoplasm staining with MET4 antibody). There was no association between MET IHC status and PFS when treated with or without cabozantinib.InterpretationThe ECOG-ACRIN 1512 trial design tested the feasibility of using cabozantinib alone or combined with erlotinib in this patient population with EGFR wild-type NSCLC. Despite its modest sample size, this trial identified signals of clinically meaningful efficacy superior to that of erlotinib alone, and additional toxicity that was generally manageable. Cabozantinib-based regimens are promising for further investigation in this patient population.

Analysis of second- and third-line antihypertensive treatments after initial therapy with an angiotensin II receptor blocker using real-world Japanese data.

Combination therapy using two or three classes of drugs is often required to treat hypertension to prevent cardiovascular disease. In this study, we examined combination therapies administered following initial therapy with an angiotensin II receptor blocker (ARB) in hypertensive Japanese patients. To determine which classes of antihypertensives are being prescribed as second- or third-line treatments for patients who were initially treated with a single ARB, we analyzed prescription claims data from two Japanese health-care databases for 2008 to 2015. Among the 26 998 patients who were initially treated with a single ARB (from one database), calcium channel blockers (CCBs) were the most frequently prescribed second-line antihypertensive, as these medicines were added for >20% of patients within 1 year of ARB prescription initiation. The addition rates of CCBs as a second-line therapy differed depending on the initial ARB type. In contrast, <10% of patients received a diuretic as a second-line antihypertensive. Among the 48 813 patients who were prescribed an ARB in combination with a CCB (as shown in the other database), diuretics were prescribed as third-line antihypertensives more frequently than increased doses of CCBs or ARBs. Diuretics were added for 8% of patients within 2 years of CCB addition, and the addition rates differed based on the CCB dose used for combination therapy. We also found that the addition rates of diuretics differed depending on patient clinical histories among ARB and CCB recipients.

Progress on clinical application of bevacizumab for the treatment of refractory cervical cancer

Bevacizumab is increasingly used in recurrent, persistent or metastatic cervical cancer. The early retrospective case reports found that bevacizumab combined with 5-FU (including capecitabine) or paclitaxel was well tolerated and displayed encouraging anti-tumor activity in recurrent or persistent cervical cancer. Phase Ⅱ clinical trials showed that bevacizumab was well tolerated and active in the second- and third-line treatment of patients with recurrent cervical cancer. Large scale phase Ⅱ and phase Ⅲ clinical trials demonstrated that bevacizumab-containing chemotherapy was effective in the first- and second-line treatment of patients with persistent cervical cancer, prolonged survival time and improved remission rate. The article also reviews the research progress on predictive factors of bevacizumab efficacy, showing the use of imaging and biomarkers in predicting the efficacy of bevacizumab treatment. In addition, this article analyzes the cost-effectiveness of bevacizumab, finding that bevacizumab combined with chemotherapy meets the standard of cost-effectiveness.

Avelumab (MSB0010718C; anti-PD-L1) + best supportive care (BSC) vs BSC ± chemotherapy as third-line treatment for patients with unresectable, recurrent, or metastatic gastric cancer: The phase 3 JAVELIN Gastric 300 trial.

TPS4135Background: Programmed death-1 receptor ligand (PD-L1) is a key therapeutic target in the reactivation of the immune response against multiple cancers. Avelumab* is a fully human anti-PD-L1 ...

Comparison of erlotinib and pemetrexed as second-/third-line treatment for lung adenocarcinoma patients with asymptomatic brain metastases.

ObjectiveBrain metastases occur in one-third of all non-small-cell lung cancer patients. Due to restrictive transport at the blood–brain barrier, many drugs provide poor control of metastases in the brain. The aim of this study was to compare erlotinib with pemetrexed as second-/third-line treatment in patients with lung adenocarcinoma with asymptomatic brain metastases.MethodsFrom January 2012 to June 2014, all lung adenocarcinoma patients with asymptomatic brain metastases who received treatment with erlotinib or pemetrexed as second-/third-line treatment were retrospectively reviewed. Chi-square and log-rank tests were used to perform statistical analysis.ResultsThe study enrolled 99 patients, of which 44 were positive for EGFR mutation. Median progression-free survival (PFS) in months was not significantly different between the erlotinib- and pemetrexed-treated groups (4.2 vs 3.4 months; 95% confidence interval [CI]: 2.01–6.40 vs 2.80–5.00, respectively; P=0.635). Median PFS was found to be significantly longer in EGFR mutation–positive patients in the erlotinib-treated group (8.0 months; 95% CI 5.85–10.15) compared to the pemetrexed group (3.9 months; 95% CI: 1.25–6.55; P=0.032). The most common treatment-related side effect was mild-to-moderate rash and the most common drug-related side effects in the pemetrexed-group were vomiting and nausea.ConclusionErlotinib and pemetrexed may be used as second-/third-line treatment in lung adenocarcinoma patients with asymptomatic brain metastases, and detection of EGFR mutation status is very important in these patients. EGFR mutation–positive lung adenocarcinoma patients with asymptomatic brain metastases showed longer PFS when treated with erlotinib as opposed to pemetrexed.

Avelumab (MSB0010718C), an anti-PD-L1 antibody, as a third-line treatment in patients with advanced gastric or gastroesophageal junction cancer: A phase Ib JAVELIN Solid Tumor trial.

TPS188 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against cancer. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in clinical trials. The phase Ib study (NCT01772004) is an open-label, parallel-group expansion trial in patients (pts) with locally advanced or metastatic (LA/M) solid tumors that includes a heavily pretreated cohort of pts with advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJ) to evaluate safety and efficacy of avelumab in the 3rd-line setting. Prior to adding this 3rd-line cohort, this trial had enrolled a separate cohort with advanced GC/GEJ who had received prior 1st-line chemotherapy (Chung et al, ECC 2015). Methods: This trial cohort is enrolling pts with histologically confirmed unresectable LA/M GC/GEJ who have been previously treated with 1st-line combination chemotherapy and 2nd-line ramucirumab, alone or in combination, and whose disease has progressed during or after ramucirumab treatment. Pts who have received prior treatment with trastuzumab and pts with HER2+ status are allowed. Eligible pts also must have tumor archival material or fresh biopsy, an ECOG performance status of 0 or 1 at the time of trial entry, and disease with ≥ 1 measurable lesion according to RECIST 1.1. Exclusions include prior therapy with immune checkpoint drugs or history of autoimmune disease. Up to 150 eligible pts will receive avelumab at 10 mg/kg as an IV infusion Q2W. Treatment will continue until disease progression, unacceptable toxicity, or any criterion for withdrawal occurs. Primary endpoint is confirmed best overall response (RECIST 1.1) as adjudicated by an IERC. Secondary objectives include assessment of progression-free survival, overall survival, and immune-related efficacy assessments. Association between tumor PD-L1 expression and efficacy will be evaluated. Adverse events will be assessed and graded according to NCI-CTCAE v4.0. Tumor evaluation will be performed every 6 wks until progression. Enrollment in this cohort began in June 2015. *Proposed INN Clinical trial information: NCT01772004.

Clinical observation of docetaxel combined with carboplatin as second-or third-line treatment for patients with advanced triple-negative breast cancer

Objective To observe the clinical efficacy and adverse reactions of docetaxel and carboplatin 21 day regimen (TC) as second-or third-line in treatment of patients with advanced triple-negative breast cancer (ATNBC). Methods 37 ATNBC patients with anthracyclines resistance were given docetaxel 70mg/m2, the first day of intravenous drip, carboplatin AUC=5, through intravenous drip on the first day, 21 days for a course of treatment, until disease progression or not tolerated or most received six cycles of chemotherapy. Results 147 cycles of chemotherapy were completed in 37 patients, and the median chemotherapy cycle was 4 cycles.The efficacy and adverse reactions could be evaluated in all patients.Among them, complete remission (CR) in 0 patient, partial remission (PR) in 12 patients (32.43%), stable (SD) in 11 patients (29.73%), and progression(PD) in 14 patients (41.18%). The effective rate(CR+ PR) was 32.43%.The disease control rate (CR+ PR+ SD) was 62.15%, median TTP was 3.9 months (95%CI: 4-8months), and median OS was 10 months.Until the end of follow-up, there were 3 patients with no progress.The main adverse reactions were hematological toxicity (51.53%) and gastrointestinal reaction (56.76%). Conclusion TC regimen is effective and safe in the treatment of patients with ATNBC. Key words: Breast cancer; Docetaxel; Carboplatin

Cost Effectiveness Analysis of Eribulin Mesylate as a Treatment for Metastatic Breast Cancer in Spain: Management in the Later Line of Therapy.

Background: Two thirds (62%) of metastatic breast cancer (MBC) patients in Western Europe have human epidermal growth factor receptor 2 (HER2)-negative disease, for which anthracyclines and taxanes are recommended as first-line treatments, followed by microtubule-targeting agents such as capecitabine, vinorelbine and/or eribulin. The study objective was to compare the cost-effectiveness of eribulin in Spain as a second-line treatment for HER2-negative MBC with its current status as a third-line treatment for patients who have received capecitabine. Methods: A Markov model was developed from the perspective of the Spanish healthcare system. The model had three health states: Stable; Progression and Death. In Stable, patients received eribulin or: capecitabine and vinorelbine for HER2-negative patients; primary treatment of physician's choice (TPC) for post-capecitabine patients. In Progression, all patients received secondary TPC. Model inputs were overall survival, progression-free survival and costs relating to chemotherapies, grade 3/4 adverse events and healthcare utilization. Sensitivity analyses were conducted to identify uncertainty. Results: As second-line treatment, Eribulin was associated with a greater incremental benefit in life years (LYs) and quality-adjusted life years (QALYs) than capecitabine and vinorelbine. Erubilin as third-line treatment was associated with greater benefit in life years (LYs) and QALYs than TPC. The incremental cost-effectiveness ratios (ICERs) for eribulin were higher in the second-line than the third-line setting in terms of LYs (€35,149 versus €24,884) and QALYs (€37,152 versus €35,484). In both settings, deterministic sensitivity analyses demonstrated that the ICER is most sensitive to the eribulin price. Conclusion: Eribulin is cost-effective as second-line treatment for HER2-negative MBC patients in Spain; albeit, slightly less so than as third-line treatment for MBC patients who have received capecitabine (an ICER per QALY difference of €1,668). This difference may fall within the margin of error for the model and could potentially be addressed by a minor reduction in the eribulin price.

A randomized, open-label, multi-center phase II study to compare bevacizumab plus sorafenib versus sorafenib for the third-line treatment of patients with metastatic renal cell carcinoma (NCT02330783).

e15591 Background: There is no standard treatment in patients with renal cell carcinoma that was previously treated with VEGF-targeted therapies and mTOR inhibitors. From the Gold study, Sorafenib ...

113P - Anlotinib as Third-Line Treatment in Patients with Refractory Advanced Non-Small Cell Lung Cancer: a Multicentre, Randomized, Double-Blind, Placebo-Controlled, Phase Ii Trial (NCT01924195)

113P - Anlotinib as Third-Line Treatment in Patients with Refractory Advanced Non-Small Cell Lung Cancer: a Multicentre, Randomized, Double-Blind, Placebo-Controlled, Phase Ii Trial (NCT01924195)