Doxophos (doxorubicin nanoparticle formulation) / Hetero, Vivesto - LARVOL DELTA

STANDARD-RISK RANDOMIZATION OF PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA IN TRIAL AIEOP-BFM ALL 2000 INDICATES EQUAL OUTCOME WITH REDUCED-INTENSITY DELAYED INTENSIFICATION IN ETV6-RUNX1-POSITIVE PATIENTS (EHA 2017) - "P-III is shorter than P-II (duration 29 vs 49 days), the dose of dexamethasone in P-III is 30% lower, and the dose of vincristine, doxorubicin, and cyclophosphamide are reduced by 50% as compared to P-II. There was no evidence of prognostic disadvantage in ETV6-RUNX1-positive standard-risk patients when treated with the reduced-intensity experimental arm. No clear age- or response-dependent differences could be revealed for this group, which is in line with the biologic understanding of this genetic subgroup.nHence, it might be postulated that treatment reduction might be feasible in this clearly defined biologic subgroup."

Retrospective data • Acute Lymphocytic Leukemia • Biosimilar

EFFECTIVENESS OF LAWSONIA INERMIS (HENNA) FOR THE MANAGEMENT OF PALMAR-PLANTAR ERYTHRODYSESTHESIA: PRELIMINARY RESULTS FROM A RANDOMISED CONTROLLED TRIAL (MASCC-ISOO 2017) - P=N/A; "To test the effectiveness of a henna treatment protocol in the management of capecitabine and/or pegylated liposomal doxorubicin induced palmar-plantar erythrodysesthesia.The preliminary findings showed the henna was more effective to reduce the PPE grade compared to the placebo."

Clinical • HEOR • Biosimilar • Oncology

13-YR FOLLOW UP OF MULTICENTER RANDOMIZED CHOP-R VS R-HDS TRIAL IN HIGH RISK FOLLICULAR LYMPHOMA PATIENTS: PROLONGED SURVIVAL AND HIGH RATE OF LONG-TERM DISEASE FREE SURVIVORS (EHA 2017) - P3; "Treatment schedule consisted of: i. CHOP-R arm: 6 courses of cyclophosphamide/doxorubicin/vincristine/prednisone followed by 4-weekly rituximab courses; ii. i. poor risk FL may have a prolonged survival, with 63% of patients alive at 13 yrs.; ii. no survival differences between CHOP-R and R-HDS can be detected even at 13 yrs of follow-up; iii."

Clinical • Biosimilar • Indolent Lymphoma

INNOVATE: a phase II study of TTFields (200 kHz) concomitant with weekly paclitaxel for recurrent ovarian carcinoma (AACR 2017) - "97% of patients received prior taxane-containing regimens, 16% received prior bevacizumab and 58% received prior pegylated-liposomal doxorubicin (PLD). TTFields concomitant to weekly paclitaxel are tolerable and safe in heavily pre-treated platinum-resistant ovarian cancer ovarian cancer patients, with promising progression-free and overall survival. A phase III trial is planned, testing the efficacy of TTFields combined with paclitaxel in recurrent ovarian cancer patients."

P2 data • Biosimilar • Gynecologic Cancers • Oncology • Ovarian Cancer

KPT-9274 inhibits cellular NAD and synergizes with doxorubicin to treat dogs with lymphoma (AACR 2017) - P1; "KPT-9274 exhibits single agent activity in canine spontaneous cancers. Moreover, the combination of KPT-9274 and DOX has substantial biologic activity against canine Non-Hodgkin lymphoma, likely through the activation of NAD consuming enzymes such as PARP1 by DOX. Importantly, the drug combination was safe with no enhanced toxicity over DOX alone."

Biomarker • Late-breaking abstract • Biosimilar • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sarcoma • Venous Thromboembolism

Breast conservation after neoadjuvant chemotherapy for triple-negative breast cancer: Surgical results from an international randomized trial (BrighTNess). (ASCO 2017) - P3; " Women with operable TNBC were randomized to veliparib (V) with carboplatin (C) and paclitaxel (P), placebo with C and P or placebo with P followed by doxorubicin and cyclophosphamide. This largest prospective analysis of the impact of NST in TNBC demonstrates a conversion rate from BCT-I to BCT-E of 53%. BCT rates were lower in pts with gBRCA; the much higher mastectomy rate among BCT-E pts in NA merits investigation."

Clinical • Biosimilar • Triple Negative Breast Cancer

A randomised phase III trial comparing two dose-dense, dose-intensified approaches (EPC and PM(Cb)) for neoadjuvant treatment of patients with high-risk early breast cancer (GeparOcto). (ASCO 2017) - P3; "...Background: The sequential use of intense does-dense (idd) epirubicin, paclitaxel, cyclophosphamide (EPC) and weekly paclitaxel/liposomal doxorubicin (+/- carboplatin (Cb) in triple negative breast cancer (TNBC) (PM(Cb)) are considered highly efficient regimens for high-risk early stage breast cancer (BC)...For HER2+ BC trastuzumab 6 (8) mg/kg q3w and pertuzumab 420 (840) mg q3w cycles were given concomitantly with P and C. Pts with histologically confirmed, cT1c - cT4a-d BC and central receptor assessment were included... In high-risk early stage breast cancer pts pCR rates of idd EPC compared to weekly PM(Cb) were not significantly different. PM(Cb) appeared to be less feasible."

Adverse events • Clinical • P3 data • Biosimilar • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Immunology • Triple Negative Breast Cancer

Effects of neoadjuvant chemotherapy (NAC) on tumor infiltrating lymphocytes (TIL) and PD-L1 expression in the SWOG S0800 clinical trial. (ASCO 2017) - P2; "The goal of this study was to examine TIL and PD-L1 expression in pre- and post-NAC tumor specimens from the S0800 clinical trial that compared weekly nab-paclitaxel/bevacizumab + dose-dense doxorubicin and cyclophosphamide (AC) with nab-paclitaxel + AC as NAC for HER2-negative cases. TIL counts and PD-L1 expression generallydecreased, but in a minority of cases increased after NAC. The decrease in TIL was significantly greater in cases achieving pCR."

Biomarker • Clinical • Biosimilar • Oncology

NCT02456857: A phase II trial of liposomal doxorubicin, bevacizumab and everolimus (DAE) in patients with localized triple-negative breast cancer (TNBC) with tumors predicted insensitive to standard neoadjuvant chemotherapy (AACR 2017) - P2; "Abstract embargoed at this time."

Clinical • P2 data • Biosimilar • Breast Cancer • Oncology • Triple Negative Breast Cancer

Results of the GETUG-AFU 19 trial: A randomized phase II study of dose dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) with or without anti-epidermal growth factor receptor (EGF-R) monoclonal antibody panitumumab (PANI) in advanced transitional cell carcinoma (ATCC). (ASCO-GU 2017) - P3; "When combined with dd-MVAC, PANI does not seem to improve efficacy in pts with ATCC."

Biomarker • Clinical • P2 data • Biosimilar • Oncology • Ophthalmology • Prostate Cancer • Urothelial Cancer

A phase I window, dose escalating and safety trial of Metformin in combination with induction chemotherapy (VPLD)in relapsed/refractory acute lymphoblastic leukemia: NCT01324180 (AACR 2017) - P1; " Metformin was administered twice daily continuously on a 28 day cycle in addition to the Vincristine, Dexamethasone, PEG-Asparaginase and Doxorubicin (VPLD) systemic regimen and CNS-directed therapy in pediatric patients with relapsed/refractory ALL. This trial has been completed. We found induction of ER stress with inhibition of UPR consistent with that observed in vitro leading to metformin-induced apoptosis. The chemotherapeutic backbone was tolerable and the combination with metformin yielded responses in a heavily pretreated population."

Adverse events • P1 data • Acute Lymphocytic Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Oncology

Pressurized intraperitoneal aerosol chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) in patients with gastric cancer and peritoneal metastasis (PIPAC-GA1). (ASCO-GI 2017) - P2; "PIPAC C/D is well tolerated and active in patients with RGCPM. Survival is encouraging. Randomized controlled trials should now be designed."

Clinical • Biosimilar • Gastric Cancer • Gastrointestinal Cancer • Oncology

Genomic predictors of neoadjuvant chemotherapy (NACT) response in breast cancer (BC). (ASCO 2017) - P2; " Baseline (BL) and post-NACT tumor / matched normal DNA from 12 newly diagnosed BC patients on NACT (4 x doxorubicin/cyclophosphamide + low dose sunitinib; NCT01176799) were subject to whole exome sequencing. Chemoresistance and emergent mutations were revealed by tracking mutant VAF in BC patients on NACT."

Biomarker • Clinical • Biosimilar • Breast Cancer

SWOG S0221 updated: Randomized comparison of chemotherapy schedules in breast cancer adjuvant therapy. (ASCO 2017) - P3; "Background: S0221 investigated weekly vs q 2 week dosing of doxorubicin/cyclophosphamide (AC) and paclitaxel (P) in patients (pts) with high risk early breast cancer as previously reported (JCO 33:58-64, 2015). There were no significant differences in DFS or OS between any of the schedules with extended follow-up in the original cohort and no difference in outcome by paclitaxel schedule for the 578 additional patients in the revised protocol. Either paclitaxel schedule may be recommended, with selection based on toxicity, cost, or patient preference rather than efficacy."

Clinical • Biosimilar • HER2 Breast Cancer • Hormone Receptor Breast Cancer

Ixazomib as a Replacement for Carfilzomib and Bortezomib for Multiple Myeloma Patients (clinicaltrials.gov) - P1/2; N=60; Recruiting; Sponsor: Oncotherapeutics; Trial primary completion date: Dec 2016 ➔ Dec 2017

Trial primary completion date • Biosimilar • Hematological Malignancies • Multiple Myeloma • Oncology

Safety Study of Rituximab (SC) Administered in Participants With CD20+ DLBCL or CD20+ Follicular NHL Grade 1 to 3A (clinicaltrials.gov) - P3; N=121; Active, not recruiting; Sponsor: Hoffmann-La Roche; Recruiting ➔ Active, not recruiting

Enrollment closed • Biosimilar • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

ZoptEC: Zoptarelin Doxorubicin (AEZS 108) as Second Line Therapy for Endometrial Cancer (clinicaltrials.gov) - P3; N=512; Completed; Sponsor: AEterna Zentaris; Active, not recruiting ➔ Completed

Trial completion • Biosimilar • Endometrial Cancer • Oncology • Uterine Cancer

Doxorubicin Hydrochloride, Cisplatin, and Paclitaxel or Carboplatin and Paclitaxel in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer (clinicaltrials.gov) - P3; N=1331; Active, not recruiting; Sponsor: Gynecologic Oncology Group; N=900 ➔ 1331; Trial primary completion date: Jan 2008 ➔ Jun 2013

Enrollment change • Trial primary completion date • Biosimilar • Endometrial Cancer • Oncology • Uterine Cancer

Costs Associated with Treatment Induced Peripheral Neuropathy in Patients with Multiple Myeloma By Lines of Therapy (ASH 2016) - "Methods: Adult patients with ≥1 inpatient or 2 outpatient claims (within 30 - 365 days) with a diagnosis of MM (ICD-9-CM code 203.0x) and ≥1 claim indicating the administration or prescription of a MM therapy (bendamustine, bortezomib, carfilzomib, cisplatin, cyclophosphamide, doxorubicin, doxorubicin liposomal, lenalidomide, melphalan, pomalidomide, thalidomide) on or after the date of the first found MM diagnosis in 7/1/2006 - 3/31/2015 were extracted from MarketScan claims databases. TIPN is prevalent (15.3%) in patients with MM; it adds to the cost of MM treatment in earlier lines of therapy. Effective novel treatments that do not add to the economic burden associated with TIPN are needed to manage MM."

Clinical • HEOR • Biosimilar • Gene Therapies • Hematological Malignancies • Multiple Myeloma • Oncology • Pain • Renal Disease

Characterization of neuroendocrine breast carcinomas for biomarkers of therapeutic options (SABCS 2016) - "Therapeutic biomarkers (IHC) that may guide chemotherapies (and used in other primary sites neuroendocrine tumors) included: high TOP2A (85%) for etoposide or doxorubicin, low TS (57%) for 5-fluorouracil and low ERCC1 (45%) for cisplatin. Additional biomarkers for chemotherapy included: high TOPO1 (60%) for irinotecan, low RRM1 (48%) for gemcitabine and low MGMT (57%) for temozolomide. Molecular profiling by a multiplatform approach reveals potential personalized therapy options for this very rare breast cancer subtype. With recent success of somatostatin analogs for other neuroendocrine tumors, the overexpression of SSTR gene family in NBC is worthy of further investigation."

Biomarker • Clinical • Biosimilar • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Triple Negative Breast Cancer

Crizotinib and Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma (clinicaltrials.gov) - P1; N=65; Recruiting; Sponsor: Children's Oncology Group; Trial primary completion date: Apr 2017 ➔ Oct 2018

Trial primary completion date • Biosimilar • Breast Cancer • Diffuse Large B Cell Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Therapy for Children With Advanced Stage Neuroblastoma (clinicaltrials.gov) - P2; N=150; Recruiting; Sponsor: St. Jude Children's Research Hospital; Trial primary completion date: Sep 2018 ➔ Jan 2021

Trial primary completion date • Biosimilar • Oncology

I-SPY 2 TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer (clinicaltrials.gov) - P2; N=1920; Recruiting; Sponsor: QuantumLeap Healthcare Collaborative; Trial primary completion date: May 2018 ➔ Dec 2018

Trial primary completion date • Biosimilar • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology

Ibrutinib for untreated mantle cell lymphoma (clinicaltrialsregister.eu) - P2/3; N=400; Ongoing; Sponsor: Plymouth Hospitals NHS Trust

New P2/3 trial • Biosimilar • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Pre-clinical drug screen reveals topotecan, actinomycin D and volasertib as potential new therapeutic candidates for ETMR brain tumor patients. (PubMed) - Neuro Oncol - "BT183 cells are very sensitive to the topoisomerase inhibitors topotecan and doxorubicin, to the epigenetic agents decitabine and panobinostat, to actinomycin D, and to targeted drugs such as the PLK1 inhibitor volasertib, aurora kinase A inhibitor alisertib, and the mTOR inhibitor MLN0128. Finally, using multi-agent treatment regimens of topotecan or doxorubicin combined with methotrexate and vincristine the response in tumor growth and survival was further increased compared to mice receiving single treatments. We have identified several promising candidates for combination therapies in future clinical trials for ETMR patients."

Journal • Biosimilar