bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized, double-blinded, phase II study of paclitaxel/carboplatin (PC) plus CT-322 versus PC plus bevacizumab (Bev) as first-line treatment for advanced nonsquamous non-small cell lung cancer (NSCLC).
Authors: Paschold Eugene Henry , Mazieres Julien , Lena Hervé , Cruciani Giorgio , Laird Glen , Walters Ian B. , Chen Allen C. , Trifan Ovidiu C. 
Published: March 2020

7584 Background: CT- 322 is a pegylated protein engineered from the tenth type III human fibronectin domain thatspecifically blocks VEGFR-2 signaling by all known ligands. This international randomized study assessed the efficacy and safety of PC + CT-322 compared to PC + Bev as first-line treatment for advanced non-squamous NSCLC. Methods: In addition to paclitaxel 200 mg/m2and carboplatin AUC 6 given on day 1 of a 21 day cycle(maximum 6 cycles), subjects, stratified by ECOG performance status, disease stage, and site, were randomized 1:1 to receive either CT-322 2 mg/kg on days 1, 8, and 15 (arm A) or Bev 15 mg/kg on day 1 and placebo on days 8 and 15 (arm B). CT -322 and Bev/placebo were continued as maintenance until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), response rate, and safety. Results: 255 subjects were randomized to arm A (n=127) or arm B (n=128). Baseline characteristics were wellbalanced. After a median follow- up of 13.8 months, 9 subjects on arm A and 24 on arm B remained on study treatment. The median treatment duration was 19 weeks in arm A and 26.3 weeks on arm B. The median PFS in arm A was 5.6 months compared to 6.8 months in arm B (HR 1.51, 1 -sided p=0.997). In all prespecified subgroups, PFS was favored in arm B. The response rate was 25.2% in arm A compared to 32.8% in arm B. Median OS was 12.5 months in arm A compared to 15.2 months in arm B. The most common grade ≥ 3 adverse events (Arm A vs B) were neutropenia (47.2% vs 49.2%), thrombocytopenia (11.8% vs 6.3%), and fatigue (10.2% in both arms). Grade ≥ 3 hypertension was more frequently reported in arm A (8.7% vs 3.1%). Grade ≥ 3 venous thrombosis (5.5% vs 6.3%), proteinuria (1.6% vs 2.3%), and bleeding events (0.8% vs 1.6%) were similar. Conclusions: PC + CT-322 failed to improve PFS, OS, or response rate compared to PC + Bev. However, thesafety profile in the PC + CT-322 arm was consistent with the anti-angiogenic mechanism of action, suggesting that CT-322 has biological activity as an inhibitor of VEGFR-2.
Clinical characteristics of KRAS mutations in NSCLC and their impact on outcomes to first-line chemotherapy.
Authors: Butaney Mohit , Porter Jennifer , Lindeman Neal Ian , Janne Pasi A. , Rabin Michael S. , Marcoux J Paul , Johnson Bruce E. , Jackman David Michael 
Published: March 2020

7588 Background: KRAS is one of the most commonly mutated oncogenes in non-small cell lung cancer (NSCLC). While the impact of EGFR mutations and EML4-alk translocations has been well-described, there is limited information about the impact of these somatic mutations on response to chemotherapy. Methods: We retrospectively reviewed the demographics and clinical outcomes of patients with KRAS mutations and compared these to patients who were KRAS wild-type (WT). Eligible pts received 1st-line IV chemo for stage IV NSCLC at DFCI and had known information about both KRAS and EGFR status. Since the biology and impact of EGFR mutations on response to chemo is well-described, we excluded such pts from the analysis. The primary endpoint was progression-free survival (PFS) with first-line chemo; secondary endpoints included radiographic response rate (RR) and overall survival (OS). Results: Between 2/05 and 8/11, there were 63 eligible KRAS pts and 97 eligible WT pts. The groups were similar in age (median 65yrs in both groups), % female (K 62, WT 54) race (K 89% white/6% black, 5% other; WT 86% white,/6% black/8% other), histology (K 90%adeno/8% NSCLC NOS; WT 86% adeno/9%NSCLC NOS), and % of pts receiving 1/2/3 agents in 1st line (K 11/56/33; WT 18/53/30). KRAS pts were less likely to be never or light smokers (4% vs 33% for WT). Nonsmokers were more likely to harbor KRAS transition rather than transversion mutations (3 transition, 1 transversion), while the converse held for smokers (51 transversions, 8 transitions). Median PFS was similar for KRAS vs WT (K .65 vs WT 4.8 months, p=0.81). RR (29% for both groups), disease control rates (K 73% vs WT 78%), and median OS (K 13.5 vs WT 12.1 months, p=.525) were also similar. Outcomes of KRAS pts to 2nd line chemotherapy (PFS 2.2, OS 8.6) are similar to those seen for WT patients in this setting. There was no significant difference in outcomes based on gender, smoking status, drug received (pemetrexed-based vs taxane based), or specific KRAS genotype. Conclusions: Pts with KRAS mutations experience similar outcomes to standard chemotherapy as those who are wild-type for EGFR and KRAS. Going forward, these data can serve as a reference for control arms of KRAS-specific randomized trials.
Safety and efficacy analysis by histology of weekly nab-paclitaxel in combination with carboplatin as first-line therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC).
Authors: Renschler Markus Frederic , Okamoto Isamu , Hon Jeremy K. , Hirsh Vera , Dakhil Shaker R. , Page Ray D. , Orsini James , Zhang Hui , Socinski Mark A. 
Published: March 2020

7592 Background: Treatment of advanced NSCLC differs by histology, with fewer options and poorer outcomes in pts with squamous histology. In a phase III trial of nab-paclitaxel (nab-P, 130 nm albumin-bound paclitaxel particles) + carboplatin (C) vs solvent-based paclitaxel (sb-P) + C, the primary endpoint of ORR was significantly improved from 25% to 33%, p = 0.005, with a 1-month improvement in OS (p = NS) and improved safety. This analysis evaluated efficacy and safety by histology. Methods: Pts with untreated stage IIIB/IV NSCLC were randomized 1:1 (stratified by age, histology, region, stage, and gender) to C AUC 6 day 1 and either nab-P 100 mg/m2 on days 1, 8, 15 or sb-P 200 mg/m2 day 1 q 21 days. ORR and PFS were determined by blinded centralized review. Results: In squamous pts, nab-P/C produced a significantly higher ORR (41% vs 24%, p < 0.001), similar PFS (5.6 vs 5.7 mo, HR: 0.865) and >1-month improvement in OS (10.7 vs 9.5 mo, HR: 0.890) vs sb-P/C (Table). nab-P/C was as effective as sb-P/C in nonsquamous pts for ORR (26% vs 25%, p = 0.808), PFS (6.9 vs 6.5 mo, HR: 0.933), and OS (13.1 vs 13.0 mo, HR: 0.950). In both squamous and nonsquamous pts, nab-P/C vs sb-P/C produced lower rates of grade 3/4 neuropathy (3% vs 11% and 3% vs 12%, respectively, p < 0.001 both), neutropenia (43% vs 51%, p = NS, and 50% vs 63%, p = 0.008), and higher but manageable rates of anemia (27% vs 4% and 28% vs 9%, p < 0.001 both) and thrombocytopenia (21% vs 7% and 16% vs 11%, p < 0.001 both). Conclusions: In pts with advanced NSCLC, nab-P/C demonstrated a favorable risk-benefit profile as a first-line therapy regardless of histology. Significantly improved ORR and a positive trend in OS were observed in pts with squamous histology. [Table: see text]
Meta-analysis of progression-free survival as a predictor of overall survival in locally advanced or metastatic non-small cell lung cancer trials.
Authors: Turner Evadne Jane , McCloud Philip , Germanos Peter , Dehle Francis , Norris Sarah , Tan Jonathan 
Published: March 2020

7604 Background: Access to new oncology treatments for non-small-cell lung cancer (NSCLC) could be expedited if progression free survival (PFS) was accepted by payers as a valid endpoint predictive for overall survival (OS). We investigated the relationship between PFS and OS in advanced NSCLC, which has previously been limited by available data. Methods: A systematic review of the published literature was conducted (1988 to August 2011; Medline/Embase/Cochrane). Identified studies were assessed against the following criteria for inclusion in the analysis: randomised design; NSCLC; advanced disease (Stage IIIb or IV); pharmacological treatment in 2 or more groups; reported outcomes included median OS and median PFS. For each pair of treatment groups compared, the median OS difference and the median PFS difference were calculated. The data were analysed with locally weighted least squares regression (LOWESS) to validate the linear relationship. Unweighted and weighted linear regression was used to test the significance of the relationship between OS difference and PFS difference. Results: A total of 124 clinical trials, with 40,568 patients, were included in the analysis. The studies ranged from middle aged cohorts to the elderly. Median performance status (ECOG/WHO) was 1. 70% of studies were first line and therapy type was predominantly chemotherapy (57%). 19 studies (15%) reported use of crossover or rescue therapy. Weighted linear regression demonstrated a highly significant linear relationship between OS difference and PFS difference (Table). The results suggest that a 1 month difference in PFS is associated with approximately 1.3 months difference in OS. Conclusions: Analysis of NSCLC trials showed the treatment effect on PFS was predictive of the treatment effect on OS. With increased use of multiple lines of treatment and crossover/rescue therapy in new NSCLC trials OS differences are frequently confounded, making PFS an important outcome for health care decision making. [Table: see text]
ABVD (8 cycles) versus BEACOPP (4 escalated cycles => 4 baseline) in stage III-IV high-risk Hodgkin lymphoma (HL): First results of EORTC 20012 Intergroup randomized phase III clinical trial.
Authors: Carde Patrice P. , Karrasch Matthias , Fortpied Catherine , Brice Pauline , Khaled Hussein Mustafa , Caillot Denis , Gaillard Isabelle , Bologna Serge , Ferme Christophe , Lugtenburg Pieternella , Morschhauser Franck , Aurer Igor , Coiffier Bertrand , Cantin Guy , Seftel Matthew D. , Wolf Max , Glimelius Bengt , Sureda Anna , Mounier Nicolas 
Published: March 2020

8002 Background: Escalated BEACOPP and derivatives achieved superior time to treatment failure (FFTF) over COPP/ABVD, resulting in higher overall survival (OS) for advanced HL. However, later clinical trials have failed to confirm OS superiority over ABVD. Methods: Eligibility criteria: clinical stage III/IV HL, International prognostic score (IPS) ≥ 3, age<60. We compared ABVD (8 cycles) vs. BEACOPP (escalated 4 cycles ≥ baseline 4), without irradiation. Randomization was stratified for institution and IPS. Primary endpoint was EFS, defined as treatment discontinuation, no complete response (CR) after 8 cycles, progression, relapse or death. Additional endpoints were CR, progression free survival (PFS), OS, quality of life and secondary malignancies. Outcomes were reviewed by study coordinators to ensure consistency across pts. Results: From 2002-2010, 549 pts were randomized (ABVD 275, BEACOPP 274): stage IV 74%, PS 0, 1, 2: 34, 48 and 17%, B-symptoms 81%, median age 35.2y, males 75%. IPS was 4 or higher for 59% of pts. Histology reviewed no HL in 4 cases. CR was 83% in both arms. With a median follow-up of 3.8 yrs, EFS at 4 yrs was 63.7% vs. 69.3% (HR = 0.86, 95%CI=0.64 to 1.15, p=0.312). PFS at 4 yrs was 72.8% vs. 83.4% (HR = 0.58, 95%CI=0.39 to 0.85, p=0.005). OS at 4 yrs was 86.7 vs. 90.3 (HR = 0.71, 95%CI=0.42 to 1.21, p=0.208). Toxic deaths occurred in 6 and 5 pts, with early discontinuation (prior to cycle 5) in 12 & 26 pts, respectively. There were 5 crossovers to BEACOPP and 10 to ABVD. Second malignancies occurred in 8 ABVD and 10 BEACOPP pts (myelodysplasia/leukemia 2 and 4, lung 2 and 1, NHL 3 and 2, other 1 and 3); cumulative incidence curves did not differ significantly. Conclusions: The primary endpoint (EFS) was similar between treatment arms. However, more progressions/relapses were observed with ABVD, while early discontinuations were more frequent with BEACOPP. Nevertheless, even in this high-risk group, OS was not improved with BEACOPP. Additional considerations (treatment burden and cost, fertility issues, long term relapses and immediate and late morbidity) may guide physician/patient decisions toward ABVD or BEACOPP.
A subgroup analysis of small lymphocytic and marginal zone lymphomas in the Eastern Cooperative Oncology Group protocol E4402 (RESORT): A randomized phase III study comparing two different rituximab dosing strategies for low tumor burden indolent non-Hodgkin lymphoma.
Authors: Williams Michael E. , Hong Fangxin , Kahl Brad S. , Gascoyne Randy D. , Wagner Lynne I. , Krauss John C. , Horning Sandra J. 
Published: March 2020

8007 Background: Management of low tumor burden (LTB) indolent lymphoma in the rituximab (R) era is uncertain. We hypothesized that R could delay the need for chemotherapy and that maintenance R (MR) would be superior to R retreatment (RR) at progression. E4402 is a randomized phase III study comparing MR and RR for previously untreated, LTB (by GELF criteria) small lymphocytic lymphoma (SLL), marginal zone lymphoma (MZL) and FL. Results for the FL subset was previously presented (Kahl, et al. Blood 2011; 118(21): LBA 6); we now report outcomes for the non-FL patients (pt). Methods: Pt received R 375 mg/m2 weekly x 4, with responders randomized to MR (1 dose R q 3 mo) or RR (R q wk x 4 at progression), each continued until treatment failure. The primary endpoint, time to treatment failure (TTTF), was defined as progression within 6 mo of last R, no response to RR, initiation of alternative therapy, or inability to complete protocol therapy. Pt were evaluated q 3 mo, with CT scans q 6 mo. Secondary endpoints: time to first cytotoxic therapy (TTCT), quality of life (QOL) and safety. Results: From 11/03 to 9/08,137 non-FL pt were enrolled. Complete or partial response was achieved in 57 (41%), who were randomized to MR (n=32) or RR (n=25). 136 pt were stage III-IV (1 IE), and all had PS 0-1; for MR vs RR, median age 66 vs 64, and M:F 47:53% vs. 28:72%, respectively. The mean no. of R doses/pt (incl. 4 induction doses) was 17.9 (range 5- 30) for MR and 5.8 (range 4-12) for RR. With a median follow-up of 4.3 yr, TTTF was 3.74 yr for MR vs. 1.07 yr for RR (p=.0002; HR 4.95). At 3 yr, 100% of MR vs. 70% of RR pt (p=.0002) remained free of cytotoxic therapy. Grade 3-4 toxicities occurred in 2 MR pt, 1 neutropenia and 1 encephalopathy. Conclusions: A planned subgroup analysis of non-FL pt showed significant benefit in TTTF and TTTC for MR but with 2 grade 4 toxicities. This differs from the FL pt in this trial, for whom response to induction was higher (70 vs. 41%; p<.0001) and where no TTTF benefit was observed with MR. LTB non-follicular indolent lymphoma pt who achieve a CR or PR to induction R benefit from MR therapy.
Bendamustine, bortezomib, and dexamethasone (BVD) in elderly patients with relapsed/refractory multiple myeloma (RRMM): The Intergroupe Francophone du Myélome (IFM) 2009-01 protocol.
Authors: Rodon Philippe , Hulin Cyrille , Pegourie Brigitte , Tiab Mourad , Anglaret Bruno , Benboubker Lotfi , Jardel Henry , Decaux Olivier , Kolb Brigitte , Roussel Murielle , Garderet Laurent , Leleu Xavier , Fitoussi Olivier , Chaleteix Carine , Casassus Philippe , Lenain Pascal , Moreau Philippe , Petillon Marie-Odile , Mathiot Claire , Avet-Loiseau Herve 
Published: March 2020

8014 Background: Bortezomib (V) plus dexamethasone (D) is a treatment of choice of RRMM. In small series, the addition of an alkylator was beneficial. Bendamustine (B) showed a high activity in advanced MM. The IFM 2009-01 trial evaluates the combination of B, V and D in elderly pts with MM progressive on or after 1st line therapy. Methods: We conducted a phase 2 trial combining B 70 mg/m2 D1-8, V 1.3 mg/m2 D1-8-15-22 and D 20 mg D1-8-15-22 every 28 days. 4 cycles were administered. In responders (PR or better), 2 additional cycles were provided followed by a maintenance phase with 6 cycles given every 2 months. Inclusion criteria were progression on or after 1 prior line of therapy, measurable disease, PS ECOG <3, ANC > 1.5x109/l, platelets > 100x109/l, creatinine < 250 mcmol/l, AST and ALT < 3xULN. Pts with prior exposure to bortezomib were excluded. Response was evaluated according to IMWG criteria. Primary end point was response at end of cycle 4, secondary objectives overall response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicity. Results: The present analysis was restricted to the first 4 cycles. From 03/2010 to 07/2011, 73 pts were included, median age 75.8 years (range 66-86). Median time from diagnosis to inclusion was 29 months. All pts received only 1 prior therapy: MP in 12, MP-thalidomide in 44, lenalidomide-dexamethasone (LD) in 14, other in 3. 42 pts (57.5%) were responders at end of cycle 4 [CR: 8 (10.9%), VGPR: 9 (12.3%), PR: 25 (34.2%), SD: 10 (13.6%), progression: 11 (15%), early discontinuation: 10 (13.6%)]. 6pts/10 were in PR and 1pt/10 in VGPR at time of discontinuation. ORR was 67.1% (49/73 pts). 11 pts died (MM: 6, sepsis: 4, renal failure: 1). Adverse events grade 3-4 were neutropenia: 16 pts, thrombocytopenia: 7 pts, sepsis: 12 pts, gastro-intestinal: 8 pts, anaphylaxis: 1 pt. 2 pts had DVT. Peripheral neuropathy grade>1 occurred in 9 pts, all grade 2. Treatment was stopped in 20 pts (lack of efficacy: 11, toxicity: 9). Conclusions: These results compare favorably with those achieved with VD or LD. The triplet BVD combination is very effective and tolerable in elderly pts with MM in 1st progression.
Efficacy and side-effect profile of long-term bisphosphonate therapy in patients (pts) with multiple myeloma (MM): MRC myeloma IX study results.
Authors: Morgan Gareth J , Jackson Graham H. , Davies Faith , Wu Ping , Gregory Walter , Bell Sue E , Szubert Alexander , Navarro Coy Nuria , Drayson Mark , Owen Roger G. , Feyler Sylvia , Ashcroft John , Ross Fiona , Byrne Jennifer , Roddie Huw , Rudin Claudius , Boyd Kevin , Cook Gordon , Child J. Anthony ,   National Cancer Research Institute Haematological Oncology Clinical Study Group
Published: March 2020

8015 Background: Bisphosphonates (BPs) are recommended in pts with osteolytic lesions from MM. However, data on the long-term efficacy and safety of BPs beyond 2 y is somewhat limited. The MRC Myeloma IX study has already revealed significant overall survival (OS) and progression-free survival (PFS) benefits for zoledronic acid (ZOL) over clodronate (CLO) in MM pts (N = 1960) initiating chemotherapy (Morgan GJ, et al. Lancet. 2010). We now report the efficacy and safety of BP therapy with long-term follow-up. Methods: Newly diagnosed MM pts were randomized to ZOL (4 mg IV q 21-28 days) or CLO (1600 mg/day PO) plus antimyeloma therapy. BPs continued at least until disease progression. PFS and OS were estimated using Kaplan-Meier methodology. Hazard ratios (HRs) were calculated using stratified Cox models. Adverse events (AEs) were monitored continuously and analyzed using cumulative incidence functions. Results: At a median follow-up of 5.8 y in 1960 evaluable pts, ZOL improved PFS (HR = 0.88; P = .01) and OS (HR = 0.88; P = .03) vs CLO. Both BPs were generally well tolerated, and acute renal failure events were similar between groups (ZOL 5.2% vs CLO 5.8% at 2 y, with incidence plateaued thereafter). Overall incidence of confirmed osteonecrosis of the jaw (ONJ) has remained low (ZOL 3.7% vs CLO 0.5%; P < .0001). ONJ incidence was lower among pts receiving thalidomide-containing regimens (1.4%) vs no thalidomide (2.76%; P = .041). Events were generally low-grade, most occurred between 8 and 30 mo (median time to ONJ = 23.7 mo), and cumulative incidence plateaued at ~36 mo. Ten pts had data on ONJ recovery: complete recovery in 4 pts, improvement in 2 pts, no change in 3 pts in the ZOL group; and no change in 1 CLO pt. Dental surgery or trauma preceded ONJ in 6 ZOL pts. Conclusions: ZOL provided sustained PFS and OS improvements vs CLO during long-term therapy in the MRC Myeloma IX study. Overall incidence of AEs was similar between groups, with no notable changes during long-term therapy. ONJ incidence remained low during long-term (> 2.5 y) therapy and was reduced in pts receiving thalidomide (possibly because of anticytokine effects of this agent).
Pomalidomide (POM) with or without low-dose dexamethasone (LoDEX) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Outcomes in pts refractory to lenalidomide (LEN) and/or bortezomib (BORT).
Authors: Vij Ravi , Richardson Paul Gerard Guy , Jagannath Sundar , Siegel David Samuel DiCapua , Baz Rachid C. , Srinivasan Shankar , Larkins Gail , Zaki Mohamed H. , Hussein Mohamad A. , Anderson Kenneth Carl 
Published: March 2020

8016 Background: Response and survival outcomesare poor in pts with RRMM who are refractory to BORT and immunomodulatory drugs. POM+LoDEX has demonstrated activity in pts with advanced multiple myeloma who have received multiple lines of therapy. This analysis evaluates outcomes in pts with disease refractory to LEN, BORT, or both, as well in pts with disease refractory to both LEN and BORT who had received prior transplant. Methods: In the MM-002 phase II trial, pts received POM (4 mg/day on days 1–21 of each 28-day cycle) alone (n=108) or in combination with LoDEX (40 mg/week) (n=113). Refractory disease was defined as documented progression during treatment or within 60 days of the last dose of treatment. Response rates were assessed using European Group for Bone Marrow Transplantation (EBMT) criteria by independent adjudication committee. Results: Patients who received POM+LoDEX were refractory to LEN (77%), BORT (73%), or both (61%). Forty-two percent were refractory to both LEN and BORT and had received prior transplant. Overall, 20% of pts achieved ≥ PR, median PFS was 3.5 months, and 1-year survival rate was 59%. Response rates and duration were comparable in pts with disease refractory to LEN, BORT, or both, and in pts who had received prior transplant (response rate 25-34%, median duration of response 5.7-7 months). Survival outcomes were similar across the groups (median PFS 3.8-4.6 months; 1-year survival rate 60-67%). Conclusions: POM, given at 4 mg/day on days 1–21 of each 28-day cycle in combination with LoDEX, 40 mg/week, is effective in pts with RRMM refractory to LEN, BORT, or both, and including those with prior transplant. These results suggest a lack of cross-resistance between POM and LEN, and confirm activity not only in BORT-refractory pts but also those for whom transplant has failed. [Table: see text]