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Background The aim of this study was to evaluate patient preference and satisfaction for the subcutaneous (s.c.) versus intravenous (i.v.) formulation of rituximab given with chemotherapy in previously untreated patients with CD20+ diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Patients and methods Patients received eight cycles of rituximab according to 2 schedules: Arm A received 1 cycle rituximab i.v. (375 mg/m2) and 3 cycles rituximab s.c. (1400 mg) then 4 cycles rituximab i.v.; Arm B received 4 cycles rituximab i.v. (375 mg/m2) then 4 cycles rituximab s.c. (1400 mg). Alongside rituximab, both arms received 6–8 cycles of chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), cyclophosphamide, vincristine, prednisone (CVP), or bendamustine as per standard local practice). Preference for s.c. or i.v. administration was evaluated using the Patient Preference Questionnaire (PPQ) at cycles 6 and 8. Patient satisfaction and convenience were assessed using the Cancer Therapy Satisfaction Questionnaire (CTSQ), and Rituximab Administration Satisfaction Questionnaire (RASQ) at cycles 4 and 8. Results At the primary data cut-off (19 January 2015), the intent-to-treat population comprised 743 patients. The majority had DLBCL (63%) and baseline characteristics were balanced between arms. At cycle 8, 81% of patients completing the PPQ preferred rituximab s.c. Preference was not impacted by treatment sequence or disease type. Patient satisfaction as measured by RASQ was higher for s.c. versus i.v. CTSQ scores were similar between arms. Adverse events were generally balanced between administration routes and no new safety signals were detected. Conclusion Most previously untreated patients with CD20+ DLBCL or FL preferred s.c. to i.v. rituximab administration. Patient satisfaction with rituximab treatment was generally greater with s.c. administration. Registered clinical trial number NCT01724021 (ClinicalTrials.gov).

Background OCTOPUS, an NCRI investigator-initiated umbrella phase II trial, tests the addition of targeted agents to weekly paclitaxel (wP) in recurrent platinum-resistant/refractory ovarian cancer. The first agent tested is the dual mTORC1/mTORC2 inhibitor vistusertib (V). Preclinical studies support targeting PI3K/AKT/mTOR signalling. The combination of V and wP showed activity in ovarian high grade serous carcinoma (HGSC) in phase I. This is the first randomised trial of wP and dual mTORC1/2 inhibition in ovarian cancer. Methods In this double-blind trial, patients with platinum-resistant/refractory HGSC were randomised 1:1 to wP (80mg/m2 D1, D8, D15 of 28 day cycle) + oral V (50mg BD) or placebo (P) (D1-3, D8-10, D15-17). The primary endpoint is progression-free survival (PFS) (RECIST v1.1/GCIG CA125 criteria) and response is a key secondary end-point. A mandatory pre-treatment biopsy (if technically feasible), archival tumour tissue and serial blood samples were collected. The study uses a 3-outcome approach: significance at 10% (1-sided) for PFS indicates activity, significance at 20% also requires evidence of an improvement in response. The study has 90% power to detect a hazard ratio (HR) of 0.67. Results 140 patients were randomised; median age 63 (range: 36-86); 18% platinum-refractory; 54% had ≥3 prior therapy; 7% had prior taxane in previous 6 months (m); 66% had an image-guided biopsy at study entry. Median PFS was 4.5 vs 4.2m (HR 0.84; 80% CI 0.67 to 1.07; 1-sided p = 0.18); median OS was 9.7 vs 11.1m (HR 1.21, 80% CI 0.91 to 1.60; p = 0.80); RR (RECIST/GCIG CA125: CR+PR) was 53% vs 56% for wP+V vs wP+P respectively. Grade 3/4 adverse events were 24 vs 25%. There was significantly more gastro-oesophageal reflux (grd 1/2 10 v 0%), rash (grd 2/3 9 v 0%) and lymphopenia (grd 2/3/4 47 v 31%) on wP+V. Ongoing translational research exploring the influence of PI3K/mTOR signalling on platinum resistance and response to wP will be presented. Conclusions There was modest evidence of improvement in PFS with the addition of V, but this was not supported by response or OS. Translational research and subgroup analyses are ongoing. Clinical trial identification ISRCTN16426935. Legal entity responsible for the study NHS Greater Glasgow and Clyde/University of Glasgow. Funding AstraZeneca. Disclosure S. Banerjee: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: Clovis; Honoraria (self): Roche; Honoraria (self): Merck; Travel / Accommodation / Expenses: Nucana; Honoraria (self): Immunogen; Honoraria (self), Advisory / Consultancy: Seattle Genetics; Honoraria (self), Advisory / Consultancy: Gamamabs. A.R. Clamp: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: Clovis. J. krell: Honoraria (self), Advisory / Consultancy: AstraZeneca; Research grant / Funding (institution): Takeda. R.M. Glasspool: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Tesaro; Honoraria (self), Advisory / Consultancy: Clovis; Honoraria (self), Advisory / Consultancy: Immunogen; Honoraria (self), Advisory / Consultancy: Sotio; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Lilly/Ignyta; Travel / Accommodation / Expenses: Roche. C. Orbegoso: Full / Part-time employment: AstraZeneca. C. Gourley: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Clovis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Tesaro; Honoraria (self), Advisory / Consultancy: Foundation One; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Nucana; Honoraria (self), Advisory / Consultancy: Chugai; Research grant / Funding (institution): Aprea; Research grant / Funding (institution): Novartis. U. Banerji: Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Karas Therapeutics; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Astex; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Phoenix ACT; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): ONX; Research grant / Funding (institution): BTG; Research grant / Funding (institution): Chugai; Research grant / Funding (institution): Verastem. C. Shepherd: Full / Part-time employment: AstraZeneca. W. Brugger: Full / Part-time employment: AstraZeneca. I.A. McNeish: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Clovis; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: Takeda. All other authors have declared no conflicts of interest.

Background: In the placebo-controlled phase III SATURN study, maintenance erlotinib after first-line chemotherapy demonstrated significantly prolonged progression-free survival (PFS) and overall survival (OS) in the overall study population of patients with advanced non-small-cell lung cancer (NSCLC). Methods: After four cycles of platinum-based doublet chemotherapy, patients without progressive disease (PD) were randomised to erlotinib (150 mg/day) or placebo until PD or unacceptable toxicity. In this pre-planned analysis, data are assessed according to response to first-line chemotherapy (complete/partial response [CR/PR] or stable disease [SD]). Results: Following first-line chemotherapy, 889 non-PD patients were included in the intention-to-treat population (55% SD; 44% CR/PR

Aim: The addition of BEV to standard doublet chemotherapy (CT) improves outcomes vs CT alone in pts with mCRC. Use of more intensive triplet CT may prolong overall survival (OS), progression-free survival (PFS), increase response rates and improve resectability rates but at the expense of greater toxicity. The OPAL study examined the effect of BEV + FOLFOXIRI on PFS in pts with previously untreated unresectable mCRC. Here we report final survival and pharmacogenetic results. Methods: Eligible pts had histologically confirmed mCRC, ECOG PS ≤1 and were 18–70 years old. Pts received ≤12 cycles of FOLFOXIRI (infusional 5-fluorouracil [FU] 3200 mg/m2, folinic acid [FA] 200 mg/m2, oxaliplatin 85 mg/m2 and irinotecan 165 mg/m2) + BEV 5 mg/kg q2w (induction phase) followed by ≤40 cycles of 5-FU/FA + BEV q2w (maintenance phase). PFS was the primary endpoint; secondary endpoints included OS, proportion of pts achieving resectability, safety, and prognostic value of pharmacogenetic profiling (single nucleotide polymorphisms (SNP) for VEGF-A, VEGFR 1-3, PDGFR beta, HIF 1 alpha, Neuropilin). Results: 96 pts were enrolled. Of these, 90 received study medication and formed the safety population: 64 male, 26 female; median age 58 (range 28–71) years; ECOG performance status 0/1 in 49/41 pts; liver only disease in 35 pts. During induction phase a median number of 9.5 cycles FOLFOXIRI and BEV was administered. Relative dose intensities were 81-86% for all 4 drugs. The incidence of adverse events (AEs) was as previously reported and there were no new safety signals. during induction phase. In total, 61 serious AEs occurred in 34 pts (38%). AEs resulting in death occurred in 3 pts (3%); these were not considered treatment-related by the investigators. Median PFS was 11.1 months (m) (95% CI 9.4-12.0) and OS was 32.2m (95% CI 22.6-36.9). 52 pts were pharmacogenetically profiled and VEGFR 2 SNP 305 was associated with OS (CC–12.4m, CT–18.7m, and TT–30.1m; p = 0.038). Conclusions: FOLFOXIRI + BEV was feasible in this mCRC pt population. Survival was relevantly increased compared to standard three drug combinations in a molecularly unstratified pt population. VEGFR 2 SNPs might be prognostic for treatment with FOLFOXIRI + BEV. Disclosure: A. Stein: Roche: membership on an advisory board, corporate-sponsored research. C. Bokemeyer: Roche: corporate-sponsored research. All other authors have declared no conflicts of interest.

Background In the phase III SATURN study, maintenance erlotinib significantly prolonged progression-free survival (PFS) vs placebo in patients (pts) with advanced non-small-cell lung cancer (NSCLC) and non-progressive disease after first-line chemotherapy (Cappuzzo et al, Lancet Oncol 2010). Epidermal growth factor receptor (EGFR) expression analysis by immunohistochemistry (IHC) found no significant difference in PFS (p = 0.63) or overall survival (OS; p = 0.52) with erlotinib by EGFR IHC status (Brugger et al, J Clin Oncol 2011). Recently, Pirker at al. (Lancet Oncol 2012) presented data on EGFR expression as a predictor of OS for first-line chemotherapy plus cetuximab in the phase III FLEX study, using a novel method (H-score) to assign EGFR IHC status. We used this method to reassess samples from the SATURN study. Methods The H-score method assigns an IHC score to each pt on a continuous scale of 0–300, based on the percentage of cells at different staining intensities (Pirker et al, Lancet Oncol 2012). As per this method, the outcome-based discriminatory threshold IHC H-score for our analysis was set at 200 and existing samples were re-read and classed as low (H-score Results The original EGFR IHC analysis used samples from 370 and 372 pts in the erlotinib and placebo arms, respectively. This analysis examined existing samples from 351 and 361 pts in the erlotinib and placebo arms, respectively. PFS and OS according to EGFR IHC by different methods are shown in the Table. Table: 1271P . SATURN protocol-defined EGFR IHC+ SATURN protocol-defined EGFR IHC– EGFR IHC by H-score ≥ 200 (high) EGFR IHC by H-score EGFR IHC by H-score ≥ 10% EGFR IHC by H-score n erlotinib: 308 placebo: 313 erlotinib: 62 placebo: 59 erlotinib: 146 placebo: 157 erlotinib: 205 placebo: 204 erlotinib: 267 placebo: 287 erlotinib: 84 placebo: 74 PFS 0.69 (0.58–0.82) log-rank p 0.77 (0.51–1.14) log-rank p = 0.1768 0.68 (0.53–0.86) log-rank p = 0.0010 0.76 (0.62–0.93) log-rank p = 0.0076 0.71 (0.59–0.84) log-rank p 0.79 (0.57–1.10) log-rank p = 0.1627 OS 0.77 (0.64–0.93) log-rank p = 0.0063 0.91 (0.59–1.38) log-rank p = 0.6482 0.80 (0.62–1.05) log-rank p = 0.1099 0.80 (0.64–1.01) log-rank p = 0.0639 0.78 (0.64–0.96) log-rank p = 0.0161 0.85 (0.60–1.22) log-rank p = 0.3901 n (EGFR WT) erlotinib: 170 placebo: 157 erlotinib: 28 placebo: 27 erlotinib: 86 placebo: 84 erlotinib: 103 placebo: 97 erlotinib: 147 placebo: 144 erlotinib: 42 placebo: 37 PFS in WT 0.79 (0.63–0.99) log-rank p = 0.0336 0.65 (0.37–1.13) log-rank p = 0.1146 0.69 (0.51–0.95) log-rank p = 0.0188 0.84 (0.63–1.12) log-rank p = 0.2166 0.78 (0.62–0.99) log-rank p = 0.0400 0.69 (0.44–1.10) log-rank p = 0.1126 OS in WT 0.77 (0.60–0.99) log-rank p = 0.0402 0.64 (0.35–1.20) log-rank p = 0.1608 0.78 (0.55–1.10) log-rank p = 0.1563 0.76 (0.55–1.05) log-rank p = 0.0964 0.78 (0.60–1.02) log-rank p = 0.0698 0.72 (0.43–1.19) log-rank p = 0.2004 Note: HR Conclusions Re-scoring of EGFR IHC status in SATURN by H-score found similar benefit of erlotinib treatment in PFS or OS for subsets with high or low EGFR expression, in overall or EGFR WT populations. Disclosure W. Brugger: Financial Interest: Advisory Board. F. Cappuzzo: Financial Interest: Advisory board, F. Hoffmann-La Roche Ltd. I. Bara: Employed by F. Hoffmann-La Roche Ltd. G. Klingelschmitt: Employed by F. Hoffmann-La Roche Ltd. B. Klughammer: Stock Ownership: F. Hoffmann-La Roche Ltd Employed by F. Hoffmann-La Roche Ltd. All other authors have declared no conflicts of interest.