Search

A randomised phase II trial of single fraction or multi-fraction SABR (stereotactic ablative body radiotherapy) with atezolizumab in patients with advanced triple negative breast cancer (AZTEC trial) Abstract: BACKGROUND: In patients with advanced triple negative breast cancer (TNBC), immunotherapy has shown acceptable safety and efficacy in a PD-L1 (programmed death-ligand 1) positive population. Pre-clinical evidence has demonstrated that SABR can prime a more effective systemic anti-tumor response in combination with checkpoint inhibition. It is currently unknown if single or multi-fraction SABR scheduling synergises best with atezolizumab therapy. METHODS: This was a multi-centre, open label, phase 2 randomised trial of patients with advanced TNBC, unselected for (PD-L1) status, who had recurred at least 6 months post completion of (neo) adjuvant chemotherapy and received less than 2 lines of treatment in the metastatic setting. Participants were randomised to 20Gy SABR in 1 fraction or 24Gy SABR in 3 fractions to 1-4 sites of disease, with at least one metastasis left unirradiated. Within 5 days following the final fraction of radiotherapy atezolizumab was commenced at a dose of 1200 mg every 21 days and continued for up to 24 months, or until progression or intolerable toxicity. The primary endpoint is progression- free survival (PFS). Secondary endpoints include efficacy according to PD-L1 IHC status (positive: SP142 ≥1%) and TIL (tumour infiltrating lymphocyte) quantity, response assessment, overall survival and safety. Results presented are from interim analysis performed 18 weeks after the last patient commenced treatment. RESULTS: Fifty evaluable patients were recruited and randomised between 20th November 2018 and 12thApril 2021 with a median age of 57 [35 - 79] yrs. Thirty (60%) and 20 (40%) patients had received none or one previous line of chemotherapy in the metastatic setting, respectively. 14/40 (35%) patients were PD-L1 positive at baseline and 26/42 (62%) had TIL≥5%. Median follow-up was 17 months. The median PFS for the 20 Gy arm was 2.5 (90% CI: 1.7-4.5) months, 3.1 (90% CI: 1.8-3.9) months for the 24 Gy arm. For both arms combined, the PFS was 3.1 (90% CI: 1.8-3.9) months, with no difference between the arms, HR 1.2 (95% CI: 0.6-2.1), p=0.64. PFS by PD-L1 IHC status and TIL CONCLUSIONS: The efficacy between single and multi-fraction SABR in combination with Atezolizumab was similar and toxicity was acceptable. Efficacy was seen in PD-L1 positive and negative patients. Longer follow-up is required to assess the effect on OS.. (Research support and funding provided by the imCORE Network on behalf of F. Hoffmann-La Roche; AZTEC ClinicalTrials.gov Identifier: NCT03464942) Table 1.Response AssessmentResponse, n (%)All patients (n = 50)Patients with measurable disease (n = 32)Best objective response (non-SABR lesion)CR3 (6)2 (6)PR2 (4)2(6)NCR/NPD8 (16)0SD13 (26)13 (41)PD24 (48)15 (47)ORR (CR + PR)5 (10); 95% CI: 3-224 (12%); 95% CI: 4-29DCR (CR + PR + SD + non-CR/non-PD ≥24 weeks)a11 (22%); 95% CI: 12-377 (23%); 95% CI: 10-41aOne patient withdrew at 8 weeks and was not assessable for DCR. Citation Format: Steven David, Peter Savas, Shankar Siva, Michelle White, Michael W Neeson, Shane White, Gavin Marx, Robyn Cheuk, Michelle Grogan, Maria Farrell, Jessica Foudoulis, Annette Dempsey, Paul J Neeson, Mathias Bressel, Sherene Loi. A randomised phase II trial of single fraction or multi-fraction SABR (stereotactic ablative body radiotherapy) with atezolizumab in patients with advanced triple negative breast cancer (AZTEC trial) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD10-02.

Objectives Industry-supported decision impact studies demonstrate that Oncotype Dx (ODX) changes treatment recommendations (TR) in 24-40% of hormone receptor+/HER2- patients. ODX is not reimbursed by third-party payers in Australia, potentially resulting in more selective use. We sought to evaluate the impact of self-funded ODX on TRs. Methods Data collected included demographics, tumor characteristics, indication for ODX and pre- and post-recurrence score (RS) TR. Primary endpoint was frequency of TR change and associations with TR change were sought. Results Eighteen physicians contributed 382 patients (median age 54). A total of 232 (61%) of tumors were T1 and were grade 1, 2 and 3 in 49 (13%), 252 (66%) and 79 (21%). A total of 257 (67%) were node negative. Assay indications were: confirm need for chemotherapy (CT) (36%), confirm omission of CT (40%) and genuine equipoise (24%). RS was low (≤17) in 55%, intermediate (18-31) in 36% and high (≥32) in 9%. Thirty-eight percent of patients had TR change post-ODX. Sixty-five percent of patients recommended CT pre-ODX changed to hormone therapy alone (HT)-more likely if lower grade and if ER and/or PR > 10%. Fourteen percent of patients with pre-ODX TR for HT added CT-more likely if ER and/or PR ≤10% and if Ki67 > 15% Overall, TR for CT decreased from 47% to 24%. Conclusion Patient-funded ODX changed TRs in 38% of patients, de-escalating 65% from CT to HT and adding CT to 14% of those recommended HT. These changes were greater than an industry-funded study suggesting that physicians can identify situations where the assay may influence decisions.

OBJECTIVE: Ethnicity and migrant status result in disparities with cancer burden and survival, with communication difficulties cited as the main barrier to access. Our research team tested a communication intervention package comprising consultation audio-recordings (ARs) and question prompt lists (QPLs) for low English-speaking (LES) patients with cancer. This study explored LES patient experiences, preferences, and recommendations regarding the communication package. METHODS: Participants completed a questionnaire and qualitative interview regarding ARs and QPLs. Eligibility criteria comprised aged ≥18 years old; a consultation with an oncologist between June 1, 2015 and April 1, 2016; an Arabic, Cantonese, Greek, or Mandarin professional interpreter booked for that consultation; and randomised to receive the communication intervention. RESULTS: Eighteen patients completed the qualitative interview and 17 completed the questionnaire. Fifteen reported listening to the AR at least once. Participants reported that QPLs and ARs provide support and assistance with remembering and understanding medical information. Both resources were seen as having applicability beyond the oncology setting in regards to improving health service delivery and continuity of care. However, patients felt that individual tailoring of the resources should be considered. Patients also found it useful to share ARs with family. CONCLUSIONS: The LES participants in this study considered the ARs and QPLs useful for most, but not all contexts. Recommendations regarding delivery and use highlight that these resources should be tailored and patient-driven. Further, patients foresaw a range of additional uses for consultation ARs within the broader healthcare context.

Background: Phase 3 trials (IMpassion130, KEYNOTE-355) have shown improved efficacy with the addition of immune checkpoint modulators to chemotherapy in PD-L1 +ve aTNBC. However, unmet need remains in the ~60% of pts with aTNBC who have PD-L1 -ve tumors. Preliminary data from a multicenter phase 1b study (NCT03800836) evaluating the safety and efficacy of the oral AKT inhibitor IPAT + atezo + paclitaxel/nab-paclitaxel showed promising antitumor activity (73% confirmed objective response rate) irrespective of PD-L1 status [Schmid, AACR 2019], suggesting a potential role for the triplet independent of PD-L1 status. We report on-treatment changes in the tumor microenvironment in Cohort 2. Methods: In Cohort 2, pts with aTNBC and ≤2 prior lines of chemotherapy for aTNBC received oral IPAT 400 mg on d1-28 of cycle 1 (35-d cycle) and on d1-21 of subsequent cycles (28-d cycles). IV atezo 840 mg was given on d8 & 22 of cycle 1 and on d1 & 15 of subsequent cycles. Biopsies were collected before treatment administration during cycle 1 on d1 (C1D1) & d8 (C1D8), and on d15 of cycle 2 (C2D15). PD-L1 (VENTANA SP142 immune cell ≥1%) and CD8 expression was assessed by immunohistochemistry (IHC); % immune infiltrate was measured by H&E staining. Changes in gene expression were assessed by RNA-Seq. Gene set enrichment analysis was used to study molecular pathway activation (enrichment score [ES] >0 to 1) or inhibition (ES -1 to Results: In Cohort 2, 11 pts had PD-L1 -ve tumors at baseline and are included in the analyses below, 2 had PD-L1 +ve tumors and 3 were unevaluable for PD-L1. IHC analysis of serial biopsies from pts with PD-L1 -ve tumors showed a statistically significant increase in immune infiltrates (mean % infiltrates C1D8/C1D1=1.44; p=0.042) and a trend toward increased CD8 protein expression (mean CD8 % staining C1D8/C1D1=1.75; Kruskal-Wallis p=0.16) at the tumor center during the first week of single-agent IPAT compared with the baseline biopsy. An increase in PD-L1 expression (mean PD-L1 % infiltrating immune cells C2D15/C1D1=4.33; Kruskal-Wallis p=0.044) was seen during IPAT + atezo combination treatment. No significant changes in immune infiltrates or CD8 expression were observed after initiating atezo versus IPAT alone. As expected, MTORC1 activity decreased (ES=-0.43; p Conclusion: Inhibition of AKT signaling may remodel the microenvironment of PD-L1 -ve tumors by increasing immune infiltration, priming immune pathways, promoting tumor cell apoptosis, and inhibiting oncogenic cell proliferative pathways. To our knowledge, these are the first reports evaluating molecular changes during AKT-targeted therapy for aTNBC in the context of immunotherapy irrespective of PD-L1 status. IPAT warrants further investigation combined with atezo as treatment for PD-L1 -ve aTNBC. Citation Format: Peter Schmid, Delphine Loirat, Peter Savas, Enrique Espinosa, Valentina Boni, Antoine Italiano, Shane White, Victor Laliman, Geraldine Strasser, Kui Lin, Karen Cheng, Aruna Mani, Matthew Wongchenko, Marie-Paule Sablin, Kalpit Shah. Molecular mechanism of ipatasertib (IPAT) and its combination with atezolizumab (atezo) in patients (pts) with locally advanced/metastatic triple-negative breast cancer (aTNBC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD14-03.

Introduction Small-cell lung cancer is an aggressive disease for which the mainstay of treatment is chemotherapy. Despite good initial responses most patients will relapse. Some will receive second-line therapy with clinical benefit, but for third-line chemotherapy there is little evidence to guide treatment decisions and the benefits of treatment are unknown. This study investigated the treatment of SCLC in the third-line setting. Patients and Methods An international, multicenter retrospective analysis of patients who received at least 3 lines of chemotherapy for their SCLC was performed. Results From 2000 to 2010, 120 patients were identified from 5 centers: median age 61, 40% (n = 72) limited stage, and 79% (n = 95) Eastern Cooperative Oncology Group performance status of 0 to 1. Only 22% of these patients received 3 distinct lines of chemotherapy. The remainder were rechallenged with a chemotherapy regimen used at least once previously. Six percent received platinum-based chemotherapy in all 3 lines. In third-line, response rate was 18% and median overall survival was 4.7 months. Factors associated with longer survival included normal baseline LDH levels and response to second-line chemotherapy. On multivariate analysis only normal baseline LDH retained statistical significance. Thirty-five patients went on to receive chemotherapy beyond the third line. Conclusion Few SCLC patients receive 3 chemotherapy lines. Most patients were rechallenged with a similar regimen at least once. Response and survival in the third-line setting are modest. Lack of response to second-line chemotherapy and elevated baseline LDH level might predict lack of benefit from third-line treatment. This data set does not include patients receiving fewer lines for comparison.

Aim The potential beneficial interaction between erlotinib and chemotherapy may require sequencing or pharmacodynamic separation. The aim of this study was to evaluate the efficacy and tolerance of sequential erlotinib and gemcitabine versus gemcitabine monotherapy as first-line therapy in elderly or ECOG PS-2 patients with advanced non-small cell lung carcinoma. Methods The primary objective of this multicenter randomized Phase II study was progression-free survival (PFS). Secondary objectives were overall response rate (ORR), disease control rate, response duration, overall survival and safety. Patients were randomized to either gemcitabine (1250 mg/m2 Day 1, 8 q28 days) followed by erlotinib (150 mg/day on day 15 through day 28), (EG-arm), or gemcitabine monotherapy (1000 mg/m2 Days 1, 8, 15 q28 days), (G-arm) for up to six cycles. Results Fifty-four patients were recruited, 28 G-arm and 26 EG-arm. Overall, efficacy results were not significantly different between study arms. Median PFS and ORR for the G- versus EG-arms were 8.0 versus 10.3 weeks (hazard ratio 1.3; 95% confidence interval [0.63;2.68]; P = 0.48) and 7.1 versus 3.8 percent respectively (difference −3.30; 95% confidence interval [−17.5;10.9]). The majority of adverse events (AEs) in both arms were Grade 1–2. The commonest AEs recorded in the EG- and G-arms were rash-like events (65 percent) and nausea (42 percent) respectively. Four patients (17 percent) in EG-arm and five (16 percent) in G-arm experienced at least one treatment-related serious AE. Conclusions In this study, patients with non-small cell lung carcinoma at ECOG PS-2 or aged ≥70 years derived no efficacy advantage from sequential erlotinib in combination with gemcitabine relative to gemcitabine alone. No unexpected safety findings were noted.

Purpose: Recent randomized trials in advanced TNBC have demonstrated improved efficacy with the addition of atezo to 1L nab-PAC in patients (pts) with PD-L1+ tumors (IMpassion130 [Schmid 2018]), and with the addition of the oral AKT inhibitor IPAT to 1L PAC, particularly in pts with PIK3CA/AKT1/PTEN-altered tumors (LOTUS [Kim 2017]). Loss of PTEN, a negative regulator of AKT, has emerged as a potential mechanism for resistance to checkpoint inhibitor therapy; inhibiting the PI3K/AKT pathway has led to reversal of T-cell-mediated immunotherapy resistance [Peng 2016]. We report first results from a multicenter phase 1b study (NCT03800836) evaluating a triplet of IPAT, atezo, and PAC or nab-PAC. Methods: Eligible pts had measurable unresectable locally advanced/metastatic TNBC, ECOG performance status 0/1, and no prior systemic therapy for advanced disease. Pts were assigned to PAC 80 mg/m2 (Arm A) or nab-PAC 100 mg/m2 (Arm B), both given on days 1, 8, & 15, in combination with oral IPAT 400 mg/day on days 1-21 and IV atezo 840 mg on days 1 & 15. Cycles were repeated every 28 days until loss of clinical benefit, unacceptable toxicity, or consent withdrawal. After establishing tolerability in a safety run-in (n=6), each arm was expanded to a total of 20 pts. The primary efficacy endpoint is confirmed objective response rate (ORR) per RECIST v1.1. Tumors are assessed every 8 weeks. Results: We report preliminary efficacy and safety data up to Jan 5, 2019, for the first 26 pts enrolled (18 PAC, 8 nab-PAC). The median duration of follow-up was 6.1 (range 3.1-10.6) months. Confirmed responses were seen in 19/26 pts, giving a confirmed ORR of 73% (95% CI 53-88%). Responses were seen irrespective of PD-L1 status (9/11 [82%] PD-L1+; 6/8 [75%] PD-L1-; 4/7 [57%] PD-L1 unknown) or PIK3CA/AKT1/PTEN alteration status (5/7 [71%] Dx+, 9/11 [82%] Dx-; 5/8 [63%] Dx unknown). Treatment was generally tolerable. Grade ≥3 adverse events occurred in 14 pts (54%). The most common all-grade adverse events were diarrhea (88%; grade ≥3 19%, manageable with loperamide; no colitis was reported) and rash (including pruritic, pustular, and maculopapular rash and drug eruption: 69%; grade ≥3 27%, manageable and reversible with antihistamine and steroids). The most severe rash was grade 3 and typically occurred in cycle 1. Hyperglycemia was absent. Enrollment is ongoing. Conclusions: The triplet regimen shows promising antitumor activity (73% confirmed ORR), irrespective of biomarker status, and has manageable toxicity. This triplet regimen warrants further investigation. Citation Format: Peter Schmid, Delphine Loirat, Peter Savas, Enrique Espinosa, Valentina Boni, Antoine Italiano, Shane White, Stina M. Singel, Nimali Withana, Aruna Mani, Suwen Li, Adam Harris, Matthew Wongchenko, Marie Sablin. Phase Ib study evaluating a triplet combination of ipatasertib (IPAT), atezolizumab (atezo), and paclitaxel (PAC) or nab-PAC as first-line (1L) therapy for locally advanced/metastatic triple-negative breast cancer (TNBC) [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 CT049.

Concurrent chemoradiotherapy (CCRT) has become the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). The comparative merits of two widely used regimens: carboplatin/paclitaxel (PC) and cisplatin/etoposide (PE), each with concurrent radiotherapy, remain largely undefined. Records for consecutive patients with stage III NSCLC treated with PC or PE and ≥60 Gy chest radiotherapy between 2000 and 2011 were reviewed for outcomes and toxicity. Survival was estimated using the Kaplan-Meier method and Cox modeling with the Wald test. Comparison across groups was done using the student's t and chi-squared tests. Seventy-five (PC: 44, PE: 31) patients were analyzed. PC patients were older (median 71 vs. 63 years; P = 0.0006). Other characteristics were comparable between groups. With PE, there was significantly increased grade ≥3 neutropenia (39% vs. 14%, P = 0.024) and thrombocytopenia (10% vs. 0%, P = 0.039). Radiation pneumonitis was more common with PC (66% vs. 38%, P = 0.033). Five treatment-related deaths occurred (PC: 3 vs. PE: 2, P = 1.000). With a median follow-up of 51.6 months, there were no significant differences in relapse-free survival (median PC 12.0 vs. PE 11.5 months, P = 0.700) or overall survival (median PC 20.7 vs. PE 13.7 months; P = 0.989). In multivariate analyses, no factors predicted for improved survival for either regimen. PC was more likely to be used in elderly patients. Despite this, PC resulted in significantly less hematological toxicity but achieved similar survival outcomes as PE. PC is an acceptable CCRT regimen, especially in older patients with multiple comorbidities.

This Phase I dose-escalation study (NCT00058526) assessed the safety and immunogenicity of an anti-cancer immunotherapeutic (recombinant HER2 protein (dHER2) combined with the immunostimulant AS15) in patients with early-stage HER2-overexpressing breast cancer (BC). Sixty-one trastuzumab-naive patients with stage II-III HER2-positive BC received the dHER2 immunotherapeutic after surgical resection and adjuvant therapy. They were allocated into four cohorts receiving different doses of dHER2 (20, 100, 500 A mu g) combined with a fixed AS15 dose. Safety and immunogenicity (dHER2-specific antibody responses) were assessed. After completing the immunization schedule (three or six doses over 14 weeks) and a six-month follow-up, the patients were followed for 5 years for late toxicity, long-term immunogenicity, and clinical status. The immunizations were well tolerated, and increasing doses of dHER2 had no impact on the frequency or severity of adverse events. Few late toxicities were reported, and after 5 years 45/54 patients (83.3 %) were still alive, while 28/45 (62 %) with known disease status were disease free. Regarding the immunogenicity of the compound, a positive association was found between the dHER2 dose, the immunization schedule, and the prevalence of dHER2-specific humoral responses. Among the patients receiving the most intense immunization schedule with the highest dHER2 dose, 6/8 maintained their dHER2-specific antibody response 5 years after immunization. The dHER2 immunotherapeutic had an acceptable safety profile in early HER2-positive BC patients. dHER2-specific antibody responses were induced, with the rate of responders increasing with the dHER2 dose and the number and frequency of immunizations

The purpose of this study was to investigate the safety, tolerability, and pharmacokinetics of motesanib when combined with docetaxel or paclitaxel in patients with metastatic breast cancer. In this open-label, dose-finding, phase 1b study, patients received motesanib 50 or 125-mg orally once daily (QD), beginning day 3 of cycle 1 of chemotherapy, continuously in combination with either paclitaxel 90 mg/m(2) on days 1, 8, and 15 every 28-day cycle (Arm A) or docetaxel 100 mg/m(2) on day 1 every 21-day cycle (Arm B). Dose escalation to motesanib 125 mg QD occurred if the incidence of dose-limiting toxicities (DLTs, primary endpoint) was ≤ 33 %. If the maximum tolerated dose (MTD) of motesanib was established in Arm B, additional patients could receive motesanib at the MTD plus docetaxel 75 mg/m(2). Forty-six patients were enrolled and 45 received ≥ 1 dose of motesanib. The incidence of DLTs was33 % in all cohorts; thus, motesanib 125 mg QD was established as the MTD. Seven patients (16 %) had grade 3 motesanib-related adverse events including cholecystitis (2 patients) and hypertension (2 patients). Pharmacokinetic parameters of motesanib were similar to those reported in previous studies. The objective response rate was 56 % among patients with measurable disease at baseline who received motesanib in combination with taxane-based chemotherapy. The addition of motesanib to either paclitaxel or docetaxel was generally tolerable up to the 125-mg QD dose of motesanib. The objective response rate of 56 % suggests a potential benefit of motesanib in combination with taxane-based chemotherapy.

Background This analysis assesses the efficacy and safety of a modified FOLFOX (oxaliplatin/leucovorin [LV]/5-fluorouracil [5-FU]) regimen given with a low dose of LV. Patients and Methods Forty patients with previously untreated metastatic colorectal cancer were enrolled to receive every-2-week cycles of oxaliplatin 100 mg/m2 intravenously administered over 2 hours concurrently with LV 20 mg/m2 bolus and 5-FU 400 mg/m2 bolus, followed by a 46-hour infusion of 5-FU 2.4 g/m2. Results Thirty-nine patients received ≥ 1 oxaliplatin dose and a median of 10 treatment cycles (range, 1–13 cycles). Thirteen patients (34%) experienced grade 3/4 neutropenia, whereas 21% of patients experienced grade 3 neurotoxicity. Of 37 eligible patients, complete or partial responses were observed in 18 patients (49% [95% confidence interval (CI), 32%–66%]). The median progressionfree survival was 6.2 months (95% CI, 5.5–8.7 months) with a median overall survival of 14.2 months (95% CI, 10–20.5 months). Conclusion A modified schedule of FOLFOX using a lower than standard dose of LV provides good response and survival results with excellent safety. A comparison with a previous study undertaken in the same centers using identical inclusion/exclusion criteria but using higher doses of LV suggests that reducing the dose of LV improves safety without compromising efficacy.

Purpose: Tumor antigen-loaded dendritic cells show promise for cancer immunotherapy. This phase I study evaluated immunization with autologous dendritic cells pulsed with mannan-MUC1 fusion protein (MFP) to treat patients with advanced malignancy. Experimental Design: Eligible patients had adenocarcinoma expressing MUC1, were of performance status 0 to 1, with no autoimmune disease. Patients underwent leukapheresis to generate dendritic cells by culture ex vivo with granulocyte macrophage colony-stimulating factor and interleukin 4 for 5 days. Dendritic cells were then pulsed overnight with MFP and harvested for reinjection. Patients underwent three cycles of leukapheresis and reinjection at monthly intervals. Patients with clinical benefit were able to continue with dendritic cell-MFP immunotherapy. Results: Ten patients with a range of tumor types were enrolled, with median age of 60 years (range, 33-70 years); eight patients were of performance status 0 and two of performance status 1. Dendritic cell-MFP therapy led to strong T-cell IFNγ Elispot responses to the vaccine and delayed-type hypersensitivity responses at injection sites in nine patients who completed treatments. Immune responses were sustained at 1 year in monitored patients. Antibody responses were seen in three patients only and were of low titer. Side effects were grade 1 only. Two patients with clearly progressive disease (ovarian and renal carcinoma) at entry were stable after initial therapy and went on to further leukapheresis and dendritic cell-MFP immunotherapy. These two patients have now each completed over 3 years of treatment. Conclusions: Immunization produced T-cell responses in all patients with evidence of tumor stabilization in 2 of the 10 advanced cancer patients treated. These data support further clinical evaluation of this dendritic cell-MFP immunotherapy.

Summary Purpose: Pemetrexed and vinorelbine are active antineoplastic agents in non-small cell lung cancer (NSCLC). Phase I objectives include maximum tolerated dose (MTD) and recommended phase II dose determination, and pharmacokinetics of the pemetrexed–vinorelbine doublet in locally advanced or metastatic solid tumor patients (pts). Phase II objectives include tumor response evaluation, efficacy, and toxicity for first-line treatment of advanced NSCLC. Experimental design: Phase I pts received pemetrexed (day 1, 300–700 mg/m2) and vinorelbine (days 1 and 8, 15–30 mg/m2) every 21 days. Pharmacokinetics determined at cycle 1. Beginning with dose-level 3, folic acid and Vitamin B12 supplementation were given. Results: Thirty-one phase I pts were enrolled. MTD was pemetrexed 700 mg/m2 and vinorelbine 30 mg/m2; and recommended phase II dose was pemetrexed 500 mg/m2 and vinorelbine 30 mg/m2. When administered in combination, pemetrexed and vinorelbine pharmacokinetics were consistent with single-agent administration. Thirty-seven (36 chemonaive) phase II NSCLC pts received pemetrexed–vinorelbine. Evaluable tumor response was 40%, with intent-to-treat 38%. One drug-related death occurred from febrile neutropenia with Staphylococcal infection. Grade 3/4 hematologic toxicities were neutropenia (65%) and febrile neutropenia (11%), while prevalent grade 3/4 non-hematologic toxicity was fatigue (27%). Conclusion: The pemetrexed–vinorelbine combination is well tolerated and shows activity as first-line treatment in advanced NSCLC patients.

This study determined the efficacy and safety of a modified FOLFOX regimen that improved patient convenience without compromising oxaliplatin dose intensity. A total of 62 patients with previously untreated metastatic colorectal cancer were enrolled to receive, entirely as outpatients, 2-weekly cycles of oxaliplatin 100 mg m(-2) i.v. over 2 h, together with leucovorin 400 mg m(-2) over 2 h, 5-fluorouracil (5-FU) 400 mg m(-2), bolus, followed by a 46-h infusion of 5-FU at 2.4 g m(-2). Treatment was given until progression or unmanageable toxicity. In all, 61 patients received > or =one oxaliplatin dose and a median of 11 treatment cycles (range 1-20 cycles); 22 (36%) reported grade 3/4 neutropenia and 13 patients (21%) experienced grade 3 neurotoxicity; 16 patients (26%) discontinued treatment due to disease progression or death, 15 (25%) due to neurotoxicity and six (10%) due to haematological toxicity. Of the 56 eligible patients, complete or partial responses were observed in 29 or 52% (95% confidence interval 38-65%). Median progression-free survival was 8.2 months (7.1-9.9) and median overall survival was 18.7 months (14.0-23.4). In our experience, a modified schedule of FOLFOX improves convenience without compromising efficacy or toxicity.

Carboplatin is a platinum analogue, widely used in the treatment of numerous cancer types including lung, genitourinary and ovarian cancers. It is also used in the adjuvant treatment of human epidermal growth factor receptor 2 positive breast cancer, where a non-anthracycline regimen is preferred. It is considered generally to be less toxic though potentially less efficacious than cisplatin, another platinum compound. Cisplatin is well recognized as causing hyponatremia, through the mechanism of renal salt wasting. Conversely, carboplatin has only rarely been associated with hyponatremia. We report here a case of severe hyponatremia occurring 6 days after adjuvant treatment with a carboplatin-containing chemotherapy regimen for early stage breast cancer. The mechanism of hyponatremia was consistent with the syndrome of inappropriate anti-diuretic hormone secretion based on biochemical and clinical findings, and response to fluid restriction. With no previously reported cases of docetaxel-associated or trastuzumab-associated hyponatremia, the causative agent was considered to be carboplatin. Additionally there was no recurrence of hyponatremia on recommencement of docetaxel and trastuzumab therapy. Hyponatremia secondary to carboplatin has been rarely reported in the literature, with only three previously reported cases. Although it is rare, oncologists should be aware of the potential for carboplatin to cause hyponatremia and the need to monitor electrolytes throughout therapy.

8514 Background: Early phase trials of anti-programmed death 1 (PD-1) antibodies have demonstrated important responses in malignant mesothelioma (MM). Expression of the ligand, PD-L1, is a potential biomarker for PD-1 directed therapy use and is expressed in a significant proportion of MM. We present results for a cohort treated with PD-1 inhibitory antibodies and assessed for PD-L1 expression. Methods: Patients (pts) with unresectable pleural or peritoneal mm treated with anti-PD-1 antibodies were included. Data was collected retrospectively. Radiological response was assessed using RECIST 1.1. Overall survival (OS) and progression-free survival (PFS) were evaluated. PD-L1 expression was assessed with IHC clone E1L3N (Cell Signaling Technology). PD-L1 positivity was defined as membranous expression on tumour cells: > 5% for PD-L1+ and > 50% for PD-L1hi. Results: Forty-six pts were treated between July 2015 and January 2017. Median age was 66.5 years, ECOG PS was 0/1 in 3/46 (7%) and 35/46 (76%) respectively. Most were male (83%), and 43/46 (93%) had ≥1 prior therapy, with a median of 2 (range 0 - 5). The predominant histology was epithelioid (n = 32/46; 70%). Pembrolizumab was used in 45/46 and BGB-A317 (a PD-L1 antibody) in 1 pt. Of the 46 pts, the overall response rate (ORR) was 15% (7 PR) with 15/46 (33%) achieving stable disease, giving a DCR of 44%. Progression was seen in 24/46 (52%). Median OS for the entire cohort was 8.0 months (95% CI: 2.3 – 11.9). Median duration of response was not yet reached (range 1.5 -19.8). PD-L1 testing was performed in 14 samples, with PD-L1+ in 5 (36%) and PD-L1hi in 4 (29%). The ORR was 40% (2 PR, 3 SD) with PD-L1+, 50% (2 PR, 2 SD) with PD-L1hi and 22% (2/9 patients) with negative expression. PFS and OS were greater with both PD-L1+ (PFS HR: 0.26, 95% CI 0.05 – 1.32, p = 0.10) and PD-L1hi(PFS HR: 0.17, 95% CI 0.02 – 1.47, p = 0.11). PD-L1+ positivity remained a borderline predictor of improved survival on multivariate analysis (p = 0.06). Complete PD-L1 analysis will be presented at the meeting. Conclusions: PD-1 targeted therapy demonstrated a clinically significant response rate in this cohort of mm patients. Initial analysis suggests PD-L1 expression is correlated with improved response and survival.

Summary Background A randomised phase II study was performed to compare standard combination chemotherapy containing cisplatin and etoposide with infusional carboplatin. Patients and methods One hundred twenty patients with locally advanced/metastatic non-small-cell lung cancer or mesothelioma were enrolled. All were chemotherapy-naive and had a Karnofsky performance status of ≥50. Patients were randomised to either four cycles of bolus therapy of cisplatin 80 mg/m2 day 1, etoposide 120 mg/m2 day 1–3, or continuous infusion of carboplatin 100/m2/mg/week for six weeks. Results No patients on infusional therapy incurred grade 3–4 toxicity while in the bolus arm, grade 3 and grade 4 leucopenia occurred in 17% and 35% of patients, respectively. Grade 4 thrombocytopenia occurred in 8% of patients and there were two instances of grade 3 renal toxicity. No responses occurred in the pump arm. Eight of forty-six patients with non-small-cell lung cancer responded to treatment (response rate 17.3%) with two complete responses and six partial responses. Only one patient with mesothelioma responded to bolus therapy. There was no difference in survival for the subset of NSCLC patients. Survival for mesothelioma patients in the pump arm was superior but this was likely to be a result of early deaths in the bolus arm. Conclusions The pump arm was well-tolerated but not active, whilst combination platinum-based therapy demonstrated activity but significantly more toxicity than the pump arm. Further studies of infusional carboplatin with this schedule are not warranted.

Cancer management in the older patient is a growing concern, particularly with the increasing geriatric population and the high incidence of cancer among these individuals. Incidence of lung cancer in particular is known to rise with age. This article reviews prognosis, treatment options, and decision-making issues for both clinician and patient with respect to both non-small-cell and small-cell lung cancer in this population. Research findings dealing with response rates, survival rates, and symptom control in this age group are reviewed for radiotherapy, surgery, and for various chemotherapy agents, including gemcitabine, the taxanes, vinorelbine, and the topoisomerase 1 inhibitors. Quality- of-life issues are also addressed.

In May 2000, a 23-year-old male underwent thymectomy and adjuvant radiotherapy for Masaoka stage II thymoma with positive resection margins. In December 2003, CT and positron emission tomography (P...

Background: Cancer-Testis Antigens (CTAs) are immunogenic proteins that are poor prognostic markers in non-small cell lung cancer (NSCLC). We investigated expression of CTAs in NSCLC and their association with response to chemotherapy, genetic mutations and survival. Methods: We studied 199 patients with pathological N2 NSCLC treated with neoadjuvant chemotherapy (NAC; n = 94), postoperative observation (n = 49), adjuvant chemotherapy (n = 47) or unknown (n = 9). Immunohistochemistry for NY-ESO-1, MAGE-A and MAGE-C1 was performed. Clinicopathological features, response to neoadjuvant treatment and overall survival were correlated. DNA mutations were characterized using the Sequenom Oncocarta panel v1.0. Affymetrix data from the JBR. 10 adjuvant chemotherapy study were obtained from a public repository, normalised and mapped for CTAs. Results: NY-ESO-1 was expressed in 50/199 (25%) samples. Expression of NY-ESO-1 in the NAC cohort was associated with significantly increased response rates (P = 0.03), but not overall survival. In the post-operative cohort, multivariate analyses identified NY-ESO-1 as an independent poor prognostic marker for those not treated with chemotherapy (HR 2.61, 95% CI 1.28-5.33; P = 0.008), whereas treatment with chemotherapy and expression of NY-ESO-1 was an independent predictor of improved survival (HR 0.267, 95% CI 0.07-0.980; P = 0.046). Similar findings for MAGE-A were seen, but did not meet statistical significance. Independent gene expression data from the JBR. 10 dataset support these findings but were underpowered to demonstrate significant differences. There was no association between oncogenic mutations and CTA expression. Conclusions: NY-ESO-1 was predictive of increased response to neoadjuvant chemotherapy and benefit from adjuvant chemotherapy. Further studies investigating the relationship between these findings and immune mechanisms are warranted.

e18063Background: Racial disparities have been identified in the treatment of cancer patients worldwide, often associated with differences in outcomes. International data has shown reduction in can...

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the benefits and harms of angiogenesis inhibitors in the treatment of lung cancer when given alone, following or in combination with chemotherapy or chemo-radiotherapy (in the case of locally advanced non-metastatic NSCLC or limited stage SCLC).

We evaluated whether 18F-FDG-PET altered stage classification, management, and prognostic stratification of newly diagnosed small cell lung cancer (SCLC). We identified 46 consecutive patients undergoing staging positron emission tomography for SCLC from 1993–2008 inclusive. Updated survival data from the state Cancer Registry was available on 42 of 46 patients. PET altered stage classification in 12 of 46 (26%) patients. PET altered treatment modality in nine patients, and the target mediastinal radiation field in another three patients. Therefore, PET altered management in 12 of 46 (26%) patients. Patients with limited disease (LD) on pre-PET staging had significantly longer overall survival (OS) than those upstaged to extensive disease (ED; median 18.6 months versus 5.7 months; log-rank p

BACKGROUND: Sensory neurotoxicity is dose limiting for oxaliplatin, an effective drug in the treatment of colorectal cancer (CRC) and other malignancies. This study assessed the impact of gabapentin on oxaliplatin dose intensity and neurotoxicity. PATIENTS AND METHODS: Patients with previously untreated metastatic CRC were recruited sequentially to 2 cohorts: the first used a modified FOLFOX6 (fluorouracil/leucovorin/oxaliplatin) regimen alone with oxaliplatin 100 mg/m(2) every 2 weeks (mFOLFOX; n = 40), and the second included the addition of gabapentin (mFOLFOX+G; n = 41). Gabapentin commenced at 300 mg daily, increasing to a maximum of 600 mg 3 times daily to decrease neurotoxicity. RESULTS: Doses of gabapentin were increased in 31 of 41 patients, with 39% of patients receiving >or= 900 mg daily. The median relative dose intensity of oxaliplatin and requirement for dose reductions or delays because of neurotoxicity were similar in the 2 cohorts. There was no grade 4 neurotoxicity. Whereas grade 3 neurotoxicity was observed in 10% of patients treated with gabapentin versus 21% of patients treated with mFOLFOX alone, there was no statistically significant difference in the severity of neurotoxicity between the 2 cohorts (P = 0.89) or the time to recover from grade 2/3 neurotoxicity (P = 0.97). There were also no significant differences in nonneurologic toxicity or antitumor efficacy between the 2 cohorts. CONCLUSION: This study does not support a role for gabapentin in reducing the incidence or severity of oxaliplatin-induced sensory neurotoxicity.

Background Small cell lung cancer (SCLC) is an aggressive disease and chemotherapy (CT) is the mainstay of treatment. Despite good response rates most patients (pts) will relapse and die of this disease. Standard 1st-line CT in limited (LD) and extensive stage disease is usually etoposide with platinum (P) or CAV (cyclophosphamide, doxorubicin, vincristine). At progression, 2nd-line CT may involve re-challenging with the 1st-line regimen. For pts who progress after 2 lines of CT, there is little evidence to guide treatment decisions, and the benefit of 3rd-line CT is unclear. Objective To determine the clinical benefit of 3rd-line CT for SCLC. Study design An international multi-centre retrospective analysis of pts who received 3 lines of CT for SCLC from 2001-2011 was performed. Baseline demographics, known prognostic factors and CT details were recorded. The main end-points were response rate (RR) and overall survival (OS) after 3rd-line CT. Results A total of 124 eligible pts were identified; 59% male, median age 61, 89% ECOG 0-1, 40% LD. First-line P-based CT was given to 99% of pts, with a RR of 90%. In the 2nd-line, 70 pts (56%) were re-challenged with similar CT, with the remaining receiving either CAV or topotecan based CT, with an RR of 50%. In the 3rd-line, 35 pts (28%) were re-challenged with CT similar to a prior regimen. Only 27 pts (22%) received 3 distinct lines of CT. Median progression free survival (PFS) in the 1st, 2nd and 3rd-lines were: 9.0, 4.6 and 2.0 months respectively. The RR in the 3rd-line was 17%, with no complete responses. Median 3rd-line OS was 4.8 months. Factors associated with longer OS were: normal baseline serum LDH (p = 0.02), response to 2nd-line CT (p = 0.04) and PFS >3 months after 2nd-line CT (p = 0.05). Age, sex, initial disease stage, and CT re-challenges did not predict longer survival. After the 3rd-line, 35 pts received further CT. Conclusions In 5 cancer centres, over 10 years, few SCLC pts received 3 lines of CT. Most who received 3 lines had been re-challenged with a similar regimen at least once. OS and RR in the 3rd-line are modest. Lack of response to, or progression after 2nd-line CT may predict particular lack of benefit in the 3rd-line. Prospective research in this area is needed. Disclosure All authors have declared no conflicts of interest.

Pure Red Cell Aplasia (PRCA) is a disorder charac-terized by anemia with almost complete absence of red-cell precursors but normal platelet and white blood cell precursors. It is a recognized complication of mali-gnancies, particularly Large Granulocyte Lymphomas, CLL, Hodgkins Lymphoma and thymomas [1]. PRCA has also been associated with other solid organ malig-nancies, including breast cancer although the occur-rence is very rare [2,3]. Treatment of PRCA is usually based on oral cor-ticosteroids and cyclosporine, although other immu-nosuppressive agents have been used successfully [4]. Relapse, however, is common and often prolonged courses of immunosuppression are required [5]. There have been a number of cases where treatment of an underlying malignancy has resulted in sustained remis-sion of the PRCA [3,6]. We will describe a case of breast cancer associated with PRCA, in which treatment of the underlying breast cancer in conjunction with brief course of oral pred-nisolone has caused lasting remission. A 54-year-old lady presented with a 10 cm left fun-gating infl ammatory breast mass and fevers (Figure 1). Biopsy confi rmed a basal-like invasive ductal carci-noma HER-2 negative ER/PR negative. CT scanning on presentation revealed mild left-sided lymphade-nopathy suspicious for locally advance disease. Whole body bone scan did not reveal any evidence of meta-static disease. The initial hemoglobin (Hb) was 72 g/l. The white cell count was 21.7 9 10 (neutrophils 18.6 10

Background Mucin 1 antigen, highly expressed by epithelial ovarian cancer (EOC), is a potential target for immunotherapy. A previous successful phase 1 trial was conducted in patients with adenocarcinoma who were injected with Cvac, autologous monocyte-derived dendritic cells (DCs) incubated with mannosylated mucin 1 protein (M-FP). The present study was a phase 2 trial of Cvac in patients with advanced EOC. Methods Eligible patients had EOC with progressive disease, defined as an increase in CA125 of ≥ 25% in 1 month. The primary endpoint was CA125 response or stabilization. Peripheral blood mononuclear cells were collected by leukapheresis and cultured to generate DCs. The DC were incubated with M-FP, and after washing were prepared for injection into the patient intradermally every 4 weeks for 3 doses, then every 10 weeks for up to 12 months. Results All 28 patients recruited were evaluable for safety and 26 for efficacy. All had undergone surgery and platinum-based chemotherapy, and 57% of patients received ≥ 3 chemotherapy regimens. There were no Grade 3 or 4 toxicities considered related to Cvac. Four patients showed CA125 response or stabilization (2 patients with major responses, 1 minor response, 1 stabilization) of median duration 10.3 months (5.3–16.3 months). An additional patient had > 25% CA125 reduction (not confirmed). Conclusions Cvac immunotherapy was well tolerated. Clinical activity in EOC was evident based on decline or stabilization of CA125 in some patients, supporting ongoing development of Cvac in ovarian carcinoma and planning of additional trials of patients in remission is currently underway.

Anthracyclines are amongst the most active drugs in the treatment of breast cancer. Stealth liposomal doxorubicin (Caelyx, Doxil, Alza Pharmaceuticals Inc.) is a promising new agent under investigation for the treatment of breast cancer and other solid tumours. The liposomal encapsulation alters drug pharmacokinetics and leads to a marked change in toxicity profile compared to non-liposomal doxorubicin. The results of recently completed and ongoing clinical trials in breast cancer are reviewed.

e18559 Background: Concurrent chemoradiotherapy (CCRT) has become the standard of care for patients (pts) with unresectable stage III NSCLC. Although 60Gy of radiotherapy is accepted as the standard radiation dose, the concurrent chemotherapy regimen is idiosyncratic to the institution with PC generally reserved for older and less fit pts. We retrospectively reviewed outcomes and toxicity of two widely used regimens at our institution (Austin Health, Melbourne): weekly PC (Belani et al, 2005) versus (vs) PE given weeks 1 and 5 (SWOG 9019) each with concurrent chest radiotherapy. Methods: Charts from stage III NSCLC pts treated with radical dose CCRT between 2000-2011 were reviewed. Clinical data including demographics, toxicity, and response were reviewed. Results: A total of 83 (PC: 50, PE: 33) pts were treated. PC pts were older [median age (range) 70 year (44-83) vs 63 year (32-76); p=0.001]. Other characteristics were comparable in PC and PE groups (Table). Increased grade (gr) ≥3 neutropenia was seen with PE (39% vs 12%, p=0.008). Other gr ≥3 toxicities were similar including febrile neutropenia, esophagitis and pneumonitis. With a median follow up of 17.2 months (mo), no statistical difference in overall survival (OS) (median PC 21.3 mo vs PE 13.7 mo; p=0.690) and relapse free survival (median PC 12.0 mo vs PE 11.1 mo; p=0.934) were observed. In multivariate analysis, where treatment type and age were included in the model, only more advanced stage predicted poorer OS (p=0.045). Conclusions: PC was more likely to be used in elderly pts. Despite this, PC resulted in significantly less hematological toxicity but achieved similar survival outcomes compared to PE. PC is an acceptable CCRT regimen especially in older pts. [Table: see text]

11072 Background: Cancer-Testis Antigens (CTAs) are immunogenic molecules that have increased expression in triple negative breast cancers (TNBC), a phenotype that whilst associated with poorer survival, is chemosensitive. We investigated expression of the CTAs MAGE-A, MAGE-C1, and NY-ESO-1 in women with Locally Advanced Breast Cancers (LABC) and TNBC to determine the association between CTA expression, survival and response to chemotherapy. Methods: We reviewed patient charts, treated for either TNBC or LABC between 1997 and 2011. Tissue samples were used for immunohistochemical (IHC) staining for MAGE-A, MAGE-C1 and NY-ESO-1 and compared using Fisher’s exact test. Positive expression was defined as any antigen staining above background.. Clinicopathological features were correlated with IHC results and survival estimated using the Kaplan Meier method. Results: A total of 106 cases were investigated (64 TNBC and 42 LABC). In the TNBC cohort the median age was 58 and TNM stages 1 to 3c. CTA expression occurred in 56, 51 and 43% for MAGE-A, MAGE-C1 and NY-ESO-1 respectively. CTA expression was not associated with overall survival (OS) or time to progression. In the LABC cohort the median age was 54 and consisted of stage IIIb tumors. All breast cancer subtypes were represented. CTA expression occurred in 26, 64 and 21% for MAGE-A, MAGE-C1 and NY-ESO-1 respectively. There was no association between CTA expression and response to chemotherapy. In a univariate analysis MAGE-A expression in the LABC group was associated with poorer OS (median 25 vs 76 months, HR 3.347 95% CI 1.44 to 21.68, p=0.015). However, there were more TN patients and Grade 3 tumors in the MAGE-A positive group. Across the two groups, MAGE-A (51 vs 14% p=0.002) and NY-ESO-1 (37 vs 2% p=0.006) but not MAGE-C1 had significantly higher expression in ER -ve tumors. There was higher expression of MAGE-A (51 vs 25% p=0.025) and NY-ESO-1 (43 vs 10% p=0.002) in Grade 3 tumors. Conclusions: MAGE-A, MAGE-C1 and NY-ESO-1 are highly expressed in TNBC and high-grade subsets of early breast cancer. CTA expression in TNBC was not predictive of survival nor response to chemotherapy in LABC. However, MAGE-A expression was found to be associated with poorer overall survival in LABC.

Background There is growing evidence that older patients derive the same benefits from chemotherapy as younger patients, but often at the cost of increased toxicity. A retrospective analysis was done of cancer patients ≥65 years who received chemotherapy, with the aim of identifying patient or treatment factors associated with subsequent hospital admission. Methods Medical records and an electronic prescribing system (EPS) were used to identify all cancer patients ≥65 years who received chemotherapy at Northern Health. For each patient, age, treatment dose at onset, ECOG, presence of metastases, cardiac comorbidities, chronic kidney disease stage, liver function tests and reason for admission were documented. Univariate and multivariate logistic regression analysis was used to assess the association between a factor and subsequent hospitalisation. An Odds Ratio greater than or less than 1, and a P value Results Between June 2009 and October 2010, 102 patients ≥65 years received chemotherapy on the EPS, which assigns full dose chemotherapy unless reduced by the clinician. 35 patients had a dose reduction at the outset. 49 patients were admitted following at least one cycle of chemotherapy; 33 (67%) for a treatment complication, 12 (24%) due to a cancer related complication and 4 (8%) for other reasons. After adjusting for age there was a trend for patients on full chemotherapy dose to have a decreased risk of admission (OR 0.50, 95%CI 0.21-1.12, p = 0.116). A multivariate model found that after adjusting for age and treatment dose, there was a trend for the presence of metastases at baseline (OR 2.6, 95%CI, 0.88-4.85, p = 0.095) and the presence of cardiac comorbidities (OR 2.35, 95%CI, 0.90-6.11, P = 0.080) to be associated with an increased risk of admission. Conclusion In this cohort of 102 older patients no factors were found that accurately predicted subsequent acute care admission. Surprisingly, a lack of dose reduction did not appear to incease risk of admission, indicating that high-risk patients were being effectively identified and that the EPS was being implemented appropriately in this population of older adults. Disclosure All authors have declared no conflicts of interest.

e17539 Background: Cancer-testis antigens (CTAgs) have previously been shown to be markers of poor prognosis and to be associated with chemoresistance in short interference RNA screens. In contradistinction, we recently reported the CTAg NY-ESO-1 predicted improved responses to neoadjuvant chemotherapy in pathological stage IIIA NSCLC. Despite this, no significant survival benefit was seen in NY-ESO-1 positive (NY-ESO-1+) patients. Given that tissues available for staining in the neoadjuvant setting were limited, we investigated a retrospective cohort of patients who underwent curative surgery for pathological N2 disease. As some of these patients were operated on prior to the broad acceptance of adjuvant chemotherapy (ACT), half did not receive chemotherapy. We investigated NY-ESO-1 as a prognostic and/or predictive marker in these patients. Methods: Formalin fixed paraffin embedded tissues were reviewed and stained using standard methods for a panel of CTAgs including NY-ESO-1 by immunohistochemistry. Tumors were categorized as NY-ESO-1+ or NY-ESO-1-. Isolated DNA was subjected to mutation profiling using Sequenom’s MassArray platform. Molecular markers were correlated with clinicopathological features and survival. Results: NY-ESO-1 stained 26/104 (25%) samples, including 15 cases that received ACT and 11 that did not. NY-ESO-1+ tumors were enriched for squamous cell carcinomas over adenocarcinomas (12/29 vs. 8/57; p = 0.01). They also lacked EGFR mutants and were enriched for KRAS mutants amongst adenocarcinomas relative to NY-ESO-1- tumors (5/8 vs. 9/49; p=0.02). NY-ESO-1+ patients who did not receive ACT had significantly worse outcome than NY-ESO-1- patients who did not receive ACT (HR 2.66 1.2-5.86, p=0.01). Median survival favored NY-ESO-1+ patients who received chemotherapy (37.7 months) compared to NY-ESO-1- patients regardless of chemotherapy (28.2 ACT vs 15.7 No ACT; p= 0.25) and NY-ESO-1+ patients who did not receive ACT (7.75). Conclusions: In this dataset, NY-ESO-1 was poorly prognostic but also predictive for more favorable outcomes with chemotherapy. These data support our previous observation of increased responses to chemotherapy in NY-ESO-1+ N2 patients and warrant further study.

e11102 Background: TN breast cancers are associated with young onset, high-risk pathology, distant metastases and poor prognosis. We examined pathological features, treatment and clinical outcomes ...

e21100 Background: There are limited treatment options for TN breast cancer, as there is no role for hormone therapy or trastuzumab. Expression of CTAgs is confined to testis and cancer cells, making them ideal targets for specific vaccine treatment. We examined the expression of 4 CTAgs (MAGE-A3, NY-ESO-1, MAGE-A1, and MAGE-C1) in TN breast cancer to evaluate their potential as targets for vaccine treatment. We also investigated the association between CTAg expression and histopathologic prognostic factors. Methods: 39 patients with histologically confirmed early-stage TN breast cancer resected at Austin Hospital and The Northern Hospital from January 1, 2001 to February 28, 2009 were included. Immunohistochemical staining was performed on tissue microarrays of formalin-fixed paraffin-embedded tissues, with human testis as the positive control. We examined the proportion of tumours expressing CTAgs, percent of tumour area stained, and intensity of staining (semi-quantitative). Associations between CTAg e...

e19044 Background: 18FDG-PET is not routinely used in the initial staging of SCLC despite evidence that it alters stage classification and management. Furthermore, the association between stage classification by PET and prognosis of newly diagnosed SCLC has not previously been directly assessed. We aimed to evaluate whether PET altered stage classification, management and prognosis when used to stage newly diagnosed SCLC. Methods: We retrospectively reviewed the medical records of 46 consecutive patients undergoing PET during initial staging for SCLC at Austin Health from 1993 to 2008 inclusive. Data collected included patient demographics, stage classification before and after PET, treatment history and date of death. Statistical analysis included estimation of overall survival (OS) by the Kaplan-Meier method using the log-rank test. Results: PET altered stage classification in 12 of 46 (26%) of patients. Stage alteration led to a change in treatment modality in 9 of these 12 patients. In addition, PET altered the target radiation field in another three patients. Therefore, PET had a significant impact on management in 12 of 46 (26%) of patients. Patients with limited disease (LD) on both conventional imaging and PET had significantly longer OS than patients with LD on conventional imaging that was upstaged to extensive disease (ED) on PET (median 557 days versus 172 days; log-rank p18FDG-PET during staging for SCLC had a major impact on stage classification, management and prognostic stratification. The use of staging PET should be considered in patients with newly diagnosed SCLC. No significant financial relationships to disclose.

5515 Background: Mucin 1 (MUC1) is a glycoprotein highly expressed by ovarian carcinoma and is thus a potential antigen for immunotherapy. Following successful phase I results (Loveland et al. Clin Can Res 2006; 12:869), using DC pulsed with mannan-MUC1 fusion protein (DC-MFP), we report a phase II trial in similarly treated pts with ovarian carcinoma. Methods: Eligibility: incurable disease; age = 18 yrs; PS 0–2; no autoimmune disorders; rising CA125 levels (= 25% in 1 mth, confirmed). The primary endpoint was CA125 response (major = 50%, minor = 25%, each confirmed at = 4 wk) or stabilisation (= 3 mths). PBMC were collected by leukapheresis, cultured with IL-4 and GM-CSF to generate DC, and pulsed with MFP on d5. DC were reinjected on d6 as 8 i.d. injections (each 5x106), given 4-weekly × 3, then 10- weekly to 12 mths. Excess cells were cryopreserved for subsequent injections. Results: 28 pts were recruited, with all evaluable for toxicity and 21 for efficacy (received = 3 vaccinations). Characteristics were: serous histology 24 (86%) pts; median age 58 yrs (34–78); PS 0–1 27 (96%) pts; prior systemic therapy (all pts platinum-treated) 1 line 5 pts, 2 line 4 pts, 3 line 10 pts, = 4 lines 9 pts. Leukapheresis was generally required only 6-monthly. Following ex vivo culture, the proportion of CD86+ cells ranged from 40 - 85%. There was no grade = 3 therapy-related toxicity. Of 21 pts, 4 (19%) showed CA125 response or stabilisation. 2 pts had major response: 1 pt with 4 previous lines of systemic therapy (DC-MFP response duration 12+ mths) and 1 pt treated second line (duration 14 mths). One pt had stable disease of 7 mths duration which included 10 wks classified as minor response and one pt, treated fifth-line, had stable disease for 5 mths. An additional pt, treated fourth-line, had >25% CA125 reduction which was not confirmed by repeat CA125. CT scan results were generally concordant with CA125 status. No relationship was seen between clinical benefit and HLA type. 88% of tumours were MUC1+ on IHC. Conclusions: Study treatment was well tolerated and acceptable to pts. There was clear evidence of clinical benefit, including pts who were heavily pre-treated. This approach warrants further study in ovarian carcinoma. Supported by grants from PrimaBiomed Ltd. No significant financial relationships to disclose.

2520 Background: Therapy with monoclonal antibodies against HER2 is effective in some patients with HER2+ Stage IV breast cancer. However, many patients do not respond to antibody therapy, and pati...

3581 Background: In order to determine the neuroprotectant effect of G against oxaliplatin-induced neurotoxicity, we sequentially recruited pt cohorts in a non-randomised phase II trial to FOLFOX t...