Days In Arm Research Articles

PHASE 1B OPEN‐LABEL STUDY OF LONCASTUXIMAB TESIRINE IN COMBINATION WITH OTHER ANTICANCER AGENTS IN PATIENTS WITH RELAPSED/REFRACTORY B‐CELL NON‐HODGKIN LYMPHOMA (LOTIS‐7)

Introduction: Combining agents with different mechanisms of action may enhance treatment (Tx) efficacy in patients (pts) with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca), an FDA-approved, CD19-directed, antibody-drug conjugate indicated for R/R diffuse large B-cell lymphoma (DLBCL), showed significant efficacy and manageable toxicity in a phase 2 trial in pts with R/R DLBCL. In preclinical models, Lonca + polatuzumab vedotin (Pola) showed improved efficacy. CD20 × CD3 T-cell–engaging antibodies and Lonca target different antigens; combining these is expected to increase efficacy. The safety and activity of Lonca combined with other agents in pts with R/R B-NHL will be evaluated in LOTIS-7. Methods: LOTIS-7, a phase 1b, open-label, multicenter, multiarm study (NCT04970901), will enroll ∼200 pts with B-NHL in part 1 (dose escalation, 60 pts) and part 2 (dose expansion, 140 pts). Part 2 may include specific subpopulation(s) of B-NHL informed by part 1. Primary endpoints are frequency and severity of adverse events (AE), serious AE, dose-limiting toxicities, and frequency of AE-related dose modifications. Secondary endpoints are overall response rate; duration of response; complete response rate; progression-free, relapse-free, and overall survival; Lonca concentrations; and antidrug antibody titers. Planned arms include Lonca + Pola (arm C), glofitamab (arm E), or mosunetuzumab (arm F). Arm C enrollment is open: pts are treated with Lonca + Pola as an outpatient infusion. In part 1, arm C pts receive Lonca at escalating doses (90-150 µg/kg) and Pola (1.8 mg/kg) on day 1 of each 3-week cycle; pts in arms E and F will receive Lonca 150 µg/kg for 2 cycles, then 75 µg/kg for subsequent cycles + glofitamab (2.5 mg on cycle [C]1 day [D]8, 10 mg on C1D15, and 10 or 30 mg for C2-12 D1, arm E) or mosunetuzumab subcutaneously (5 mg on C1D1, 15 or 45 mg for C1D8, and 45 mg for C1D15 and C2-8 D1, arm F) after initial step-up dosing. Lonca Tx may continue for up to 1 year or until disease progression, unacceptable toxicity, or other discontinuation criteria. Key eligibility criteria include age ≥18 years, pathologic diagnosis of R/R B-NHL (2016 WHO classification), measurable disease (2014 Lugano classification), Tx failure/intolerance, ≥2 lines of prior therapy (LOT) for part 1 (≥1 LOT for part 2), and ECOG performance status of 0-2. Pts previously receiving a study drug could not enroll in that respective study arm. Pts who received a stem-cell transplant within 60 days (100 days for arms E/F) before study Tx; received allogeneic stem cell or solid organ transplant (arms E/F); have lymphoma with active CNS involvement, ascites, edema, or effusion; or have significant comorbidities are excluded. The study opened in December 2021; as of January 2023, 12 pts have been enrolled and 9 treated in the Lonca + Pola arm. Encore Abstract - previously submitted to ASCO 2023 The research was funded by: ADC Therapeutics SA; medical writing: CiTRUS Health Group. Keywords: aggressive B-cell non-Hodgkin lymphoma, combination therapies, ongoing trials Conflicts of interests pertinent to the abstract. B. T. Hess Consultant or advisory role ADC Therapeutics, Bristol-Myers Squibb/Celgene M. M. Solh Research funding: Partner Therapeutics Other remuneration: Bristol-Myers Squibb, Amgen, AbbVie, Seattle Genetics M. Gandhi Honoraria: GlaxoSmithKline, TG Therapeutics, Karyopharm Therapeutics, Janssen Oncology Y. Wang Employment or leadership position: ADC Therapeutics America, Inc. Stock ownership: Johnson & Johnson (immediate family member) Y. Qin Employment or leadership position: ADC Therapeutics America, Inc. Stock ownership: ADC Therapeutics America, Inc. Research funding: ADC Therapeutics America, Inc. E. Yu Employment or leadership position: ADC Therapeutics America, Inc. Stock ownership: ADC Therapeutics America, Inc., Merck, Zentalis, Karuna Therapeutics, Biomarin P. L. Zinzani Consultant or advisory role Celltrion, Gilead Sciences, Janssen-Cilag, Bristol-Myers Squibb, Servier, Sandoz, MSD Oncology, Roche, EUSA Pharma, Kyowa Kirin, Takeda, Secura Bio, TG Therapeutics, Novartis, ADC Therapeutics, Incyte, BeiGene Other remuneration: MSD Oncology, EUSA Pharma, Novartis G. P. Collins Consultant or advisory role Roche, Takeda, Incyte, Pfizer, MSD Oncology, Celgene, BeiGene, Daiichi Sankyo, Celleron Therapeutics, ADC Therapeutics Honoraria: Roche, Takeda, Gilead Sciences, Pfizer, Novartis, Daiichi Sankyo, Incyte, Celleron Therapeutics, MSD Oncology, BeiGene, ADC Therapeutics, AstraZeneca Research funding: MSD Oncology, Celgene, Bristol-Myers Squibb, Amgen, Pfizer Educational grants: Roche, Takeda Other remuneration: Roche, Takeda, Novartis, Gilead Sciences

Phase 1b open-label study of loncastuximab tesirine in combination with other anticancer agents in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (LOTIS-7).

TPS7581 Background: Combining agents with different mechanisms of action may enhance treatment (Tx) efficacy in patients (pts) with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca), an FDA-approved, CD19-directed, antibody-drug conjugate indicated for R/R diffuse large B-cell lymphoma (DLBCL), showed significant efficacy and manageable toxicity in a phase 2 trial in pts with R/R DLBCL. In preclinical models, Lonca + polatuzumab vedotin (Pola) showed improved efficacy. CD20×CD3 T-cell engaging antibodies and Lonca target different antigens; combining these is expected to increase efficacy. The safety and activity of Lonca combined with other agents in pts with R/R B-NHL will be evaluated in LOTIS-7. Methods: LOTIS-7, a phase 1b, open-label, multicenter, multiarm study (NCT04970901), will enroll ~200 pts with B-NHL in part 1 (dose escalation, 60 pts) and part 2 (dose expansion, 140 pts). Part 2 may include specific subpopulation(s) of B-NHL informed by part 1. Primary endpoints are frequency and severity of adverse events (AE), serious AE, dose-limiting toxicities, and frequency of AE-related dose modifications. Secondary endpoints are overall response rate; duration of response; complete response rate; progression-free, relapse-free, and overall survival; Lonca concentrations; and antidrug antibody titers. Planned arms include Lonca + Pola (arm C), glofitamab (arm E), or mosunetuzumab (arm F). Arm C enrollment is open: pts are treated with Lonca + Pola as an outpatient infusion. In part 1, arm C pts receive Lonca at escalating doses (90-150 µg/kg) and Pola (1.8 mg/kg) on day 1 of each 3-week cycle; pts in arms E and F will receive Lonca 150 µg/kg for 2 cycles, then 75 µg/kg for subsequent cycles + glofitamab (2.5 mg on cycle [C]1 day [D]8, 10 mg on C1D15, 10 or 30 mg for C2-12 D1, arm E) or mosunetuzumab SC (5 mg on C1D1, 15 or 45 mg for C1D8, and 45 mg for C1D15 and C2-8 D1, arm F) after initial step-up dosing. Lonca Tx may continue for up to 1 year or until disease progression, unacceptable toxicity, or other discontinuation criteria. Key eligibility criteria include age ≥18 years, pathologic diagnosis of R/R B-NHL (2016 WHO classification), measurable disease (2014 Lugano classification), Tx failure/intolerance, ≥2 lines of prior therapy (LOT) for part 1 (≥1 LOT for part 2), and ECOG performance status of 0-2. Pts previously receiving a study drug could not enroll in that respective study arm. Pts who received a stem-cell transplant within 60 days (100 days for arms E/F) before study Tx; received allogenic stem cell or solid organ transplant (arms E/F); have lymphoma with active CNS involvement, ascites, edema, or effusion; or have significant comorbidities are excluded. The study opened in December 2021; 12 pts have been enrolled and 9 treated in the Lonca + Pola arm. Clinical trial information: NCT04970901 .

A Randomized Study of Short Course (One Week) Radiation Therapy with or without Temozolomide in Elderly and/or Frail Patients with Newly Diagnosed Glioblastoma (GBM).

Short-course radiotherapy (25 Gy in 5 fractions) has been shown to be non-inferior to standard course radiotherapy in elderly and frail patients (60 Gy in 30 fractions). The purpose of this study was to determine the effects of temozolomide combined with short-course radiotherapy on the outcome of elderly and frail patients. Between January 2017 and November 2018, 90 patients (65 years old and KPS score of 50-70; 65 years old and KPS score of 80-100; and 65 years old and KPS score of 50-70) were assessed for eligibility. Nine patients were excluded because they did not meet the inclusion criteria, six patients declined to participate, and four patients were unable to complete the quality-of-life questionnaire. The remaining 71 patients were divided into two arms at random in a 1:1 ratio. Short-course radiotherapy with concurrent temozolomide and adjuvant temozolomide was given to Arm 1, while short-course radiotherapy alone was given to Arm 2. In terms of overall survival and progression-free survival, radiotherapy with concurrent temozolomide and adjuvant temozolomide outperformed short-course radiotherapy alone. The median overall survival in arm 1 was 146 days and 121 days in arm 2 (P=0.146). The median progression-free survival in arm 1 was 109.50 days, while it was 77 days in arm 2 (P=0.028). With a median follow-up time of 6 months, the quality of life at 4 weeks and 12 weeks after treatment was not different between the two arms. We concluded that adding temozolomide to short-course radiotherapy significantly improved progression-free survival and showed an increasing trend in overall survival without compromising the quality of life.

Phase 2 pilot trial of RRx-001 as an anti-mucositis agent in patients with head and neck cancer treated with chemoradiation (PREVLAR).

6078 Background: Severe oral mucositis (SOM) is a dose limiting toxicity during radiotherapy and cisplatin for head and neck cancers. The aim of this 4-arm randomized controlled pilot trial was to evaluate the efficacy of different schedules of a novel radioprotectant, RRx-001 versus standard-of-care (SOC), to reduce duration, time to onset and incidence of SOM in patients received cisplatin-based chemoradiotherapy (CRT) for oral cavity or oropharyngeal cancer (OCC). Methods: Patients with locally advanced OCC treated with definitive or postoperative CRT were randomized to receive RRx-001 by 15-minute intravenous infusion in one of three different schedules versus none. The days and severity of mucositis were prospectively evaluated. Oral mucositis was assessed weekly during and after CRT as well as 28 days after completion. The pre-specified efficacy endpoints were duration of grade 3-4 SOM, resolution of SOM, time to onset of SOM and incidence of SOM. Results: A total of 53 patients were enrolled between June 2018 and July 2019 across 11 institutions. Forty-five (out of 53) patients received study drug and were efficacy evaluable. RRx-001 were well tolerated with no associated serious adverse events. All RRx-001 arms numerically outperformed SOC on the pre-specified efficacy measures, and the greatest effect estimate was observed on Arm 1 (RRx-001 pretreatment only + CRT). The following endpoints favored treatment with RRx-001. Median SOM duration by treatment was 22 and 40 days for Arm 1 and SOC respectively. Time to onset of SOM was by 38 days (Arm 1) vs. 26 days (SOC). On Arm 1, 83% of patients had SOM resolution vs 60% on SOC). Gastrostomy requirement was reduced by 45%. No patients on Arm 1 developed grade 4 mucositis vs 30% developed grade 4 mucositis on the SOC arm. Furthermore, the incidence of oropharyngeal dysphagia, which can substantially impair nutrition, was reduced by treatment with RRx-001, occurring at 50% vs 70% for Arm 1 vs SOC respectively. Treatment with RRx-001 resulted in highly significant decrease in the duration of SOM through 60 Gy with a median SOM of 1 day vs 17 days for Arm 1 vs SOC respectively (Wilcoxon rank-sum test p < 0.001). Median cumulative cisplatin dose was significantly greater for RRx-001 Arm 1 than SOC (557.4 mg vs. 438 mg, Wilcoxon p = 0.025). Conclusions: Compared with SOC, SOM among RRx-001-treated patients given 3 different treatment schedules was less severe, of shorter duration, demonstrated delayed time to onset and resolved earlier. Overall, the incidence, duration and severity of SOM and dysphagia was reduced. The safety profile of RRx-001 was similar to SOC. These results will inform the design of a Phase 3 pivotal study of RRx-001 in the prevention of SOM in at-risk cancer patients. Clinical trial information: NCT03515538.

Reducing Acneiform Rash Induced by EGFR Inhibitors With Honeysuckle Therapy: A Prospective, Randomized, Controlled Study.

Background: Epidermal growth factor receptor inhibitors (EGFRIs), including cetuximab, erlotinib, gefitinib and icotinib, have been proven to be effective in treating colorectal cancer or lung cancer. However, most of patients who receive EGFRIs treatment experience cutaneous toxicities, such as acneiform or papulopustular rashes, which affects quality of life and leads to discontinuation of cancer therapies. Honeysuckle is a traditional herb historically used to treat skin rash for thousands of years in Eastern Asia and showed proven safety in human. Methods: To investigate whether honeysuckle therapy could control EGFRIs induced acneiform rashes, a total of 139 colorectal and lung cancer patients with EGFRIs treatments were recruited in a prospective study. Patients were randomized to 3 arms (Arm A: prophylactic treatment with honeysuckle before rash occurred; Arm B: symptomatic treatment with honeysuckle when rash occurred; Arm C: conventional treatment with minocycline and a topical solution when rash occurred). The incidences, severities and recovery time of acneiform rash were observed in each arm. Results: Honeysuckle treatment reduced incidences of EGFRIs induced acneiform rash, which were 56.5, 68.1 and 71.7% in Arm A, B and C, respectively (p = 0.280). Severities of rash (CTCAE grade 2 and 3) were significantly lower in prophylactic honeysuckle treatment (Arm A) compared to conventional treatment (Arm C) (p = 0.027), which was 10–21%, respectively. Patients with honeysuckle treatment recovered more quickly from pruritus, the median time was 22, 36 and 58 days in Arm A, B and C, respectively (p = 0.016). Conclusion: Honeysuckle was effective in reducing incidences and severities of EGFRIs induced acneiform rash, especially for prophylactic treatment.

Interim safety analysis of the DANTE trial: Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma—A randomized, open-label phase II trial of the German Gastric Group at the AIO and SAKK.

4549 Background: The DANTE study evaluates atezolizumab in the perioperative treatment of locally advanced, potentially resectable gastric or GEJ adenocarcinoma in combination with perioperative FLOT. Here, we report the protocol-defined interim safety analysis. Methods: DANTE is a multinational, prospective, multicenter, randomized, investigator-initiated, open label phase II trial. Patients (pts) with locally advanced, potentially resectable adenocarcinoma of the stomach and GEJ (≥cT2 and/or N-positive) without distant metastases are enrolled. Pts are randomized 1:1 to 4 pre-operative 2-week cycles of FLOT followed by surgery and 4 additional cycles of FLOT plus atezolizumab at 840 mg every 2 weeks, followed by a total of 8 additional cycles of atezolizumab at 1200 mg every 3 weeks as monotherapy (arm A) or FLOT alone (arm B). Primary endpoint is time to disease progression or relapse after surgery (PFS/DFS). Results: Recruitment started in Sep 2018; by Feb 2020, a total of 175 pts have been randomized. This analysis is based on the first 40 pts (20 pts in each arm). The pts had a median age of 62 y and 75% of pts had an ECOG PS of 0 in both arms. The cohort was well balanced in terms of tumor location and clinical stage. 5% of the 40 patients (overall 7.4% of 175 pts enrolled) showed microsatellite instability. 90% of pts enrolled completed all pre-operative cycles in each arm. Total number of adverse events with relation to study treatment was 154 in arm A and 148 in arm B. Total number of serious adverse events (SAE; related or not) was 16 in Arm A and 14 in arm B. 20% of pts in each arm had an SAE due to perioperative morbidity. No surgical mortality was observed. 18 and 19 pts proceeded to operation in arms A and B, respectively. Premature treatment discontinuation occurred in 2 pts in each arm: disease progression (1) and deterioration of general health condition (1) in arm A; and pts’ wish (1) and death (1) in arm B. Median hospitalization time was 15 days in arm A and 16 days in arm B. Conclusions: Perioperative atezolizumab plus FLOT is feasible and safe. The study continues recruitment. Clinical trial information: NCT03421288 .

Safety of perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: An interim safety analysis of the DANTE, a randomized, open-label phase II trial of the German Gastric Group at the AIO and the SAKK.

398 Background: The DANTE study evaluates atezolizumab in the perioperative treatment of locally advanced, potentially resectable gastric or GEJ adenocarcinoma in combination with perioperative FLOT. Here, we report the protocol-defined interim safety analysis. Methods: DANTE is a large, multinational, prospective, multicenter, randomized, investigator-initiated, open label phase II trial. Patients (pts) with locally advanced, potentially resectable adenocarcinoma of the stomach and GEJ (≥cT2 and/or N-positive) without distant metastases are enrolled. Pts are randomized 1:1 to 4 pre-operative 2-week cycles (8 weeks) of FLOT followed by surgery and 4 additional cycles of FLOT plus atezolizumab at 840 mg every 2 weeks, followed by a total of 8 additional cycles of atezolizumab at 1200 mg every 3 weeks as monotherapy (arm A) or FLOT alone (arm B). Primary endpoint is time to disease progression or relapse after surgery (PFS/DFS). Results: Recruitment started in Sept 2018; by September 2019, a total of 122 pts have been randomized. This analysis is based on the first 40 pts (20 pts in each arm). The pts had a median age of 62 y and 75% of pts had an ECOG PS of 0 in both arms. The cohort was well balanced in terms of tumor location and clinical stage. 90% of pts enrolled completed all pre-operative cycles in each arm. Total number of adverse events with relation to study treatment was 154 in arm A and 148 in arm B. Total number of serious adverse events (SAE; related or not) was 16 in Arm A and 14 in arm B. 20% of pts in each arm had an SAE due to perioperative morbidity. No surgical mortality was observed. 18 and 19 pts proceeded to operation in arms A and B, respectively. Premature treatment discontinuation occurred in 2 pts in each arm: disease progression (1) and deterioration of general health condition (1) in arm A; and pts’ wish (1) and death (1) in arm B. Median hospitalization time was 15 days in arm A and 16 days in arm B. Conclusions: perioperative atezolizumab plus FLOT is feasible and safe. The study continued recruitment. Clinical trial information: NCT03421288.

Subgroup Analyses of the Randomized GMMG Phase III Multicenter Trial Relapse Suggest Survival Benefit of Salvage Autologous Transplant Primarily in Low Risk Multiple Myeloma

Subgroup Analyses of the Randomized GMMG Phase III Multicenter Trial Relapse Suggest Survival Benefit of Salvage Autologous Transplant Primarily in Low Risk Multiple Myeloma

Tolerance of Chemoradiation in Advanced Head and Neck Cancers: Comparison Between Inpatients and Outpatients.

Concurrent chemoradiation (CCRT) is the mainstay of treatment for majority of locally advanced head and neck carcinomas (LAHNC). Addition of chemotherapy to radiotherapy increases the probability of local control and improved disease-free survival but at the cost of acute and delayed toxicities. A retrospective observational study. To compare the tolerance of CCRT and its toxicity profile amongst two groups, first arm (Arm A) being outdoor patients and the second group (Arm B) was hospitalized patients of LAHNC in an oncology centre of a tertiary care hospital. A total of 100 patients were enrolled, 50 in each arm. Overall, the most common site was oropharynx, followed by larynx and hypopharynx. 38 patients in Arm A received full 6 cycles of weekly chemotherapy with Inj Cisplatin infusion. 39 of the hospitalized patients completed 6 cycles of weekly Cisplatin, 04 patients also received 3 weekly Cisplatin. Average duration of treatment was 49.18days in arm A and 50.92days in arm B. Incidence of Grade II onwards dysphagia was 48 and 45 (96 and 90%) in Arm A and Arm B respectively; Chi Square value-0.6 (Yate's corrected); P value-0.43. Grade III oral mucositis was seen in 14% patients in Arm A and 34% patients in Arm B. 3 patients (6%) in Arm A and 14 patients (28%) in Arm B has Grade II and III hematological toxicities and nephrological toxicities. Aspiration pneumonia was seen in 2 patients (4%) in Arm A and in 4 patients (8%) in Arm B, Chi Square value-0.2 (Yate's corrected) P value-0.67. The incidence of febrile neutropenia was 3 and 10 in Arms A and B (6 and 20%) respectively. The tolerance of CCRT in hospitalized patients is marginally better, with relatively few associated complications as compared to outdoor setting. Every institute should promulgate its own guidelines regarding hospitalization of such patients.

A Randomized, Phase II Trial of Cetuximab With or Without PX-866, an Irreversible Oral Phosphatidylinositol 3-Kinase Inhibitor, in Patients With Metastatic Colorectal Carcinoma

BackgroundThe phosphotidylinositol-3 kinase (PI3K)/serine-threonine kinase/mammalian target of rapamycin signaling pathway is frequently altered in colorectal cancer (CRC). PX-866 is an oral, irreversible, pan-isoform inhibitor of PI3K. This randomized phase II study evaluated cetuximab with or without PX-866 in patients with metastatic, anti-epidermal growth factor receptor-naive, KRAS codon 12 and 13 wild-type CRC. Patients and MethodsPatients with metastatic CRC who had received both oxaliplatin and irinotecan were randomized (1:1) to cetuximab (400 mg/m2 loading then 250 mg/m2 weekly) with or without PX-866 (8 mg orally daily; arms A and B, respectively). The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate, overall survival (OS), toxicity, and correlation of relevant biomarkers with efficacy outcomes. ResultsA total of 85 patients were enrolled. The median PFS was 59 days versus 104 days for arms A (cetuximab + PX-866) and B (cetuximab alone), respectively (P = .77). OS between the 2 arms (266 vs. 333 days for arm A vs. B) were similar (P = .83). Overall toxicity, including treatment-related toxicity, was higher in arm A compared with arm B, especially in terms of all-grade nausea (66% vs. 37%), vomiting (50% vs. 29%), diarrhea (64% vs. 18%), and rash (66% vs. 37%). Grade 3 diarrhea occurred in 19% of patients in Arm A and 0% in Arm B. PIK3CA mutations and PTEN loss by immunohistochemistry were infrequently seen. ConclusionThe addition of PX-866 to cetuximab did not improve PFS, objective response rate, or OS in patients with metastatic CRC. The combination arm had greater toxicity and may have been harmful in this study.

A Randomized Comparison of Low-Dose Cyclophosphamide + G-CSF Versus G-CSF Alone Mobilization after Lenalidomide-Bortezomib-Dexamethasone (RVD) Induction in Multiple Myeloma

Introduction Autologous stem cell transplantation (ASCT) is the standard treatment in multiple myeloma (MM) for eligible patients below 70 years of age. The main mobilization treatment in Europe consists of combination of cyclophosphamide (CY) and G-CSF. It is questionable if CY is useful in mobilization. CY as an alkylating agent might also have some negative long-term effects. Bortezomib seems not to have negative impact on autologous stem cell harvesting, but prolonged use of lenalidomide might hamper mobilization. There are only a few studies regarding autologous stem cell mobilization after RVD induction. We designed this randomized study as a substudy of the Finnish Myeloma Group Study (NCT01790737) to compare the results of CY+G-CSF versus G-CSF mobilization in autologous stem cell harvesting. The primary endpoint is the percentage of patients reaching ≥ 3 x 106/kg CD34+ cells (or ≥ 6 x 106/kg for two transplants), with ≤ 2 apheresis after low-dose CY+G-CSF vs. G-CSF mobilization. Secondary endpoints are need for plerixafor, graft cellular composition and engraftment after ASCT. Patients and methods This phase 2 study will include 80 patients below 70 years of age with symptomatic MM and eligible for ASCT. At registration the patients are randomized equally to arm A) CY 2 g/m2 + G-CSF 5 μg/kg or arm B) G-CSF 10 μg/kg. Before mobilization three RVD induction cycles are given. Each 3-week RVD cycle includes lenalidomide 25 mg daily on days 1−14, bortezomib 1.3 mg/m2 subcutaneously on days 1, 4, 8, 11, and dexamethasone 160 mg/cycle. By this schedule the first harvest is estimated to be on day +10 in CY + G-CSF and on day +5 in G-CSF group. Apheresis will start with blood CD34+ level >10 x 106/l. The target cell yields for one and two grafts are ≥ 3 and ≥ 6 x 106 CD34+ cells/kg, respectively, and the minimum for one graft ≥ 2 x 106/kg. Plerixafor is given if B-CD34+ cell count is less than 10 x 106/l on days +10 or +5, respectively, or if the first apheresis product contains 0.5 x 109/l, and unsupported platelets > 20 x 109/l. Results Fifty-six patients have been included, and the mobilization data for the first 37 patients are available for analysis. The primary endpoint was reached in 90% of the patients (18/20) in arm A and in 82% (14/17) in arm B (p=NS). The median number of apheresis to reach the goal in arms A and B is one (1-3) and two (1−3), respectively (p=0.03). The median number of harvested cells in the two arms is 6.2 (2.2−12.1) and 4.8 (2.9−7.6) x 106/kg, respectively (p The median number of CD34+ cells transplanted, was 4.1 (2.2−7.3) and 3.2 (2.3−4.7) x 106/kg in arms A and B, respectively (p=0.01). In arm A the median neutrophil engraftment was on day +14 (9−28) (16 patients) and in arm B on day +15 (11−25) (15 patients) (p=0.68). The median platelet engraftment days were +13 (8−22) and +11 (8−21) in arms A and B, respectively (p=0.67). At ASCT the response rates in arm A were ≥ VGPR 65% (13/20), PR 25% (5/20), and 10% (2/20) were progressing, and the respective rates for arm B were 70% (12/17), 18% (3/17),and 12 % (2/17). Conclusions Preliminary results of this randomized mobilization substudy with a limited number of patients show no clinically significant differences between the number of harvested CD34+ autologous stem cells. However, in CY+G-CSF group the CD34+ cell target was reached by less aphereses. After short induction course of RVD it seems possible to harvest also for two autografts with G-CSF only mobilization. However, when compared to historical data the CD34+ cell counts in blood and grafts were lower than after bortezomib + dexamethasone induction, and also neutrophil engraftment seemed to be slower after lenalidomide-based induction therapy. We conclude that CY can be omitted in the mobilization regimen for MM patients who have responded to short course of RVD. Disclosures Silvennoinen:Janssen-Cilag: Research Funding; Celgene: Research Funding; Janssen-Cilag: Honoraria; Sanofi: Honoraria; Celgene: Honoraria. Porkka:BMS: Honoraria; BMS: Research Funding; Novartis: Honoraria; Novartis: Research Funding; Pfizer: Research Funding.

Guiding decongestion treatment in chronic heart failure patients. Clinical assessment or serial laboratory evaluation?

Purpose: The purpose of this study is to determine the optimal strategy of chronic monitoring of HF patients during outpatient basis, in order to prevent cardiovascular (CV) events. Methods: One hundred and thirty five patients with history of systolic heart failure were included in the study. Patients follow-up was randomly based on clinical examination only (arm A), on serial assessment of B-type natriuretic peptide (BNP) levels, or on serial echocardiography (arm C). Patients were followed up during 12 months for major CV events (death, cardiovascular hospitalization) and renal function worsening. One way ANOVA test was used for comparisons among the three arms, while chi-square test was used for comparisons between arm A (clinical arm) and the combination of arm B and arm C (laboratory arm). Results: Renal function worsening was more frequently observed in arm A (13 events vs 4 of arm B vs 11 of arm C, p=0.049). Concerning the major CV events, arm A was associated with the shorter time to event (297±15 days vs 321±13 days for arm B, vs 329±12 days for arm C), even though the difference did not reach statistical significance. The combination of two laboratory arms (arm B and arm C) leaded to fewer CV events (p=0.052). Kaplan – Meier event free survival curves for arm B and arm C (laboratory arm), vs arm A (clinical arm) are shown in figure (log rank p=0.06). ![Figure][1] Figure 1 Conclusions: Serial laboratory evaluation of HF patients reduces CV events as well as renal function worsening when compared to clinical evaluation alone. The chronic monitoring of HF patients should include echocardiography and/or natriuretic peptides, on the top of clinical assessment. [1]: pending:yes

THU0087 One single infusion of rituximab 1g might be sufficient in the long-term management of rheumatoid arthritis patients responding to a first cycle of rituximab (2 × 1g): Results of a 2-year multi-center randomized controlled trial

ObjectivesTo assess the symptomatic efficacy and the safety profile of 2 dose regimens of rituximab (RTX) in patients (pts) who had a EULAR response 6 months after a 1st cycle...

Randomized phase II study of pemetrexed plus carboplatin followed by pemetrexed versus paclitaxel plus carboplatin followed by pemetrexed in advanced nonsquamous, non-small cell lung cancer (LOGIK 0904).

8111 Background: PARAMOUNT study confirmed the improvement of overall survival with continuation maintenance chemotherapy with pemetrexed (PEM) compared with placebo after 4 cycles of cisplatin plus PEM induction chemotherapy recently. JMEN study also showed the usefulness of switch maintenance with PEM after 4 cycles of platinum doublet without PEM. In this study, we conducted the randomized phase II study comparing switch or continuation maintenance chemotherapy with PEM after standard doublet regimen. Methods: Histologically/cytologically confirmed stage IIIb or IV non-squamous NSCLC patients with mesurable disease, ECOG PS 0-1, age over 20 years and adequate organ function were eligible for the study. Randomization was stratified by gender and stage of disease. Patients received 3 cycles of PEM 500 mg/m2 plus CB AUC6 (Arm 1) or PAC 200 mg/m2 plus CB AUC6 (Arm 2). All patients with non-PD after induction chemotherapy continued PEM 500 mg/m2 until PD. Primary endopoint is progression-free survival (PFS). Results: 140 pts were enrolled and assigned to Arm 1 or Arm 2 randomly. The clinical data of 132 pts were used as full analysis set (median age 64.5 yrs (42-83), 85 male, 120 stage IV, 58 PS0, 127 adenocarcinoma, 46 never smoker). 42 pts had prior treatment including 9 sugery, 1 adjuvant chemotherapy, 24 radiotherapy and 8 others. In both arms, 50% of pts entered into the maintenance treatment with PEM after completion of 3 cycles induction chemotherapy. The median PFS was 92 days in Arm 1 and 143 days in Arm 2, respectively. Cox-proportinal Hazard ratio was 0.827, and 95% HR confidential interval was 0.563-1.248. Stratified Log-Rank test showed no significant difference in both arms. Conclusions: There was no significant difference for PFS in PEM plus CB follwed by PEM and PAC plus CB followed by PEM. Clinical trial information: 000005008.

Pure Accelerated Radiation Versus Concomitant Chemoradiation in Selected Cases of Locally Advanced Carcinoma Cervix: A Prospective Study

This non-randomized study was conducted to assess and compare the response and safety of true accelerated radiation alone to concomitant chemoradiation in locally advanced squamous cell carcinoma of the uterine cervix. Sixty patients with locally advanced squamous cell carcinoma of the uterine cervix, FIGO Stages (2009) IB2-IIIB were non-randomized to receive six fractions per week of external beam radiation (EBRT) (will be henceforth referred to as Arm A or Study arm or pure accelerated radiation arm) and five fractions per week of EBRT and chemotherapy with inj cisplatin 40mg/m(2) i.v. every Monday during the course of EBRT (will be henceforth referred to as Arm B or Control arm or chemoradiation arm). The median follow-up was 15months in both the arms. The overall treatment time was 56.54days for Arm A and 62.59days for patients in Arm B (P value<0.000**). The median EBRT time was 32.25days in Arm A and 38.85days in Arm B, a statistically significant delay for patients of chemoradiation Arm B (P value<0.000**). The response assessment at the end of the study was not statistically different among the patients in both the treatment arms (P value 0.631). The early responses to treatment with pure accelerated EBRT are non-inferior to concomitant chemoradiation and the acute toxicities are lesser.

Prospective randomised evaluation of traditional Chinese medicine combined with chemotherapy: a randomised phase II study of wild toad extract plus gemcitabine in patients with advanced pancreatic adenocarcinomas

Background:An intravenous formulated extract of the venom of the wild toad Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider, huachansu, is currently used in China for the treatment of lung, liver, pancreatic, and colorectal cancers. We performed a randomised, single-blinded, phase II clinical study of huachansu plus gemcitabine versus placebo plus gemcitabine in patients with locally advanced and/or metastatic pancreatic adenocarcinomas.Methods:Patients with tissue-proven locally advanced and/or metastatic pancreatic adenocarinoma were randomly assigned to receive either gemcitabine 1000 mg m−2 on days 1, 8, and 15 with huachansu 20 ml m−2 daily for 21 days (arm A) or placebo (arm B); treatment cycles were 28 days in length. Primary end point was 4-month progression-free overall survival (PFS); secondary end points were objective radiographical response rate (ORR), time to progression (TTP), and toxicity.Results:A total of 80 subjects were enrolled; 76 patients were evaluable (received at least 1 week therapy). Median overall survival was 160 days for arm A and 156 days for arm B (P=0.339); ORR was 9 and 3% in arms A and B, respectively (P=0.332), median TTP was 98 and 115 days, respectively (P=0.825); the median 4-month PFS was 99 and 98 days, respectively (P=0.679).Conclusion:Huachansu when combined with gemcitabine did not improve the outcome of patients with locally advanced and/or metastatic pancreatic cancer.

Phase II/III randomized study of hyperfractionated radiotherapy with concomitant cetuximab versus concomitant chemotherapy in advanced nonmetastatic head and neck cancer: Preliminary report.

e16002 Background: This is a randomized study to compare the use of cetuximab versus platinum based chemotherapy with concurrent hyperfractionated radiation therapy (HRT). Acute and late morbidity, locoregional control (LC) and disease free survival (DFS) were set as primary end points, while overall survival (OS) was set as secondary end point. Methods: Between December 2009 and May 2011, 24 patients were randomly assigned to HRT consisting of 120 cGy twice daily, for a total of 69.6 Gys in 58 fractions over 6 weeks, plus either cisplatin chemotherapy at weeks 1, 4, 6 (Arm A: 14 patients) or weekly cetuximab (Arm B: 10 patients). The overall radiation dose was the same for the two groups. The median follow up time of the whole group was 14.07 months (IQR: 5.8- 25.0 ms). Results: Overall treatment time was 72 days in arm A and 63 days in arm B (p= 0.64). Grade 3 skin toxicity was experienced in 42.9% of patients in arm A and 9.1% in arm B (p= 0.09). Grade 3 mucositis was 64.3% in arm A and 45.5% in arm B (p= 0.43). Hematologic toxicity of G3-4 occurred in 21.4% and 18% of the cases respectively (p= 0.06). The mean percent of weight loss was (13 % +/- 0.1%) in group A, and (10.75 % +/- 0.1%) in group B respectively (p=0.56). Complete response was observed in 12 (85.7%) and 100% of patients of arm A and B respectively. Partial response was achieved in the remaining 2 (14.2%) patients in arm A. Loco-regional recurrence occurred in 2 (14.2%) of the patients in arm A after partial response, and one of them died eventually due to progressive disease. Two patients developed distant metastasis, one patient in arm A and another one in arm B. As the sample size was small and events were limited, survival analysis could not be computed at this stage of the study Conclusions: Hyperfractionated radiotherapy and concurrent cetuximab seems to have less side effects compared to concurrent platinum. There's a trend of less skin, mucosal and haematological toxicity with cetuximab that might become significant as the number of patients increase. We will be able to evaluate the outcomes of the patients regarding LC, DFS and OS within 2 years.

A Phase II Study of Lapatinib in Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

This study sought to determine the efficacy and safety profile of lapatinib in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). This phase II multiinstitutional study enrolled patients with recurrent/metastatic SCCHN into two cohorts: those without (arm A) and those with (arm B) before exposure to an epidermal growth factor receptor (EGFR) inhibitor. All subjects were treated with lapatinib 1,500 mg daily. Primary endpoints were response rate (arm A) and progression-free survival (PFS; arm B). The biologic effects of lapatinib on tumor growth and survival pathways were assessed in paired tumor biopsies obtained before and after therapy. Forty-five patients were enrolled, 27 in arm A and 18 in arm B. Diarrhea was the most frequent toxicity occurring in 49% of patients. Seven patients experienced related grade 3 toxicity (3 fatigue, 2 hyponatremia, 1 vomiting, and 1 diarrhea). In an intent-to-treat analysis, no complete or partial responses were observed, and stable disease was the best response observed in 41% of arm A (median duration, 50 days, range, 34-159) and 17% of arm B subjects (median, 163 days, range, 135-195). Median PFS was 52 days in both arms. Median OS was 288 (95% CI, 62-374) and 155 (95% CI, 75-242) days for arms A and B, respectively. Correlative analyses revealed an absence of EGFR inhibition in tumor tissue. Lapatinib as a single agent in recurrent/metastatic SCCHN, although well tolerated, appears to be inactive in either EGFR inhibitor naive or refractory subjects.

Prospective evaluation of supportive care with or without CVD chemotherapy as a second-line treatment in advanced melanoma by patient’s choice

This prospective, nonrandomized multicentre, phase III study compared best supportive care (BSC) alone with cisplatin, vindesine and dacabazine-based (CVD) chemotherapy and BSC in patients with advanced melanoma. A total of 117 pretreated patients with metastatic melanoma were evaluated, 34 patients in arm A (BSC) and 83 in arm B (BSC and CVD). Primary endpoint was overall survival and secondary endpoints were disease control rate and quality of life (European Organisation for Research and Treatment of Cancer QLQ-C30). Owing to sparse recruitment of patients for randomization, the protocol has been changed based on patients' choice. Baseline characteristics were imbalanced with respect to the Karnofsky Performance Index (P=0.001), the existence of brain metastases (P=0.035) and earlier application of chemoimmunotherapy (P=0.038). Disease control was observed in 8.8% of patients in arm A and in 28.9% of patients in arm B (P=0.028). Median overall survival time was 137 days in arm A and 229 days in arm B (P=0.014). Multivariate analyses could not ascribe this prognostic benefit to CVD treatment. No significant difference in the quality of life could be found. This study could not detect clear survival benefits for polychemotherapy with CVD compared with BSC alone in patients with advanced metastatic melanoma. Interestingly, having the choice of chemotherapy or BSC alone in a second-line situation, more than 70% of patients chose polychemotherapy.

Albumin-bound paclitaxel (ab-pac) versus docetaxel for first-line treatment of metastatic breast cancer (MBC): Final overall survival (OS) analysis of a randomized phase II trial.

275 Background: We previously reported the results of a phase II study evaluating the efficacy and safety of three different dosing regimens of ab-pac and docetaxel for the first-line treatment of MBC (Gradishar et al. J Clin Oncol. 2009;27:3611-3619). Here we report final OS outcomes. Methods: Patients (N = 300) with previously untreated MBC were randomized to 1 of 4 treatment arms (arms A–D listed in table). A step-down statistical approach was used for pairwise comparisons of treatment groups. Results: Patients (N = 300) with previously untreated MBC were randomized to 1 of 4 treatment arms (arms A–D listed in table). A step-down statistical approach was used for pairwise comparisons of treatment groups. These OS data were consistent with the investigator assessment of overall response rates (ORR) and progression-free survival (PFS) that were previously published. Rates of grade (gr) 3 sensory neuropathy (SN) were 21%, 9%, 22% and 12%, respectively in arms A, B,C, and D (p= 0.082). There were no cases of gr 4 SN. The median times to improvement to ≤ gr 2 SN were 22, 22, and 20 days for arms A, B, and C and 37 days for arm D. Gr 3/4 neutropenia occurred less frequently with ab-pac vs docetaxel (gr 3: 39, 20, 35, and 19% in arms A,B,C, and D, respectively; gr 4: 5, 5, 9, and 75%, p &lt; .001 for gr 4). Conclusions: Ab-pac qw 3/4 at 150 mg/m2 resulted in a 33.8 mo OS, a longer OS than historically achieved with taxane monotherapy in MBC. The 150 mg/m2 qw 3/4 dosing regimen provided the best clinical outcome in this phase II trial in patients with MBC. [Table: see text]