- Email: [email protected]
The use of intravenous ferric carboxymaltose without erythropoiesis-stimulating agents in the treatment of anemia in cancer patients undergoing chemotherapy with or without radiotherapy
abstracts
Annals of Oncology
Consultancy: Amgen; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Bayer; Advisory / Consultancy: Servier; Advisory / Consultancy: Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Pierre Favre; Research grant / Funding (institution): Merck Serono. P. Souquet: Honoraria (self), Speaker Bureau / Expert testimony, Non-remunerated activity/ies: Sandoz (a Novartis company). M. Declerck: Full / Part-time employment: Sandoz. E. Nabirotchkina: Full / Parttime employment: Sandoz. O. Tredan: Non-remunerated activity/ies: Sandoz; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Lilly; Honoraria (self): Astra-Zeneca; Honoraria (self): MSD-Merck; Honoraria (self): BMS. All other authors have declared no conflicts of interest.
1813P
The effect of increasing doses of pegfilgrastim (Peg) on thrombocytopenia (T) in breast cancer (BC) patients (pts) receiving taxotere (Doc), doxorubicin, cyclophosphamide (TAC) and plinabulin (Plin)
D.W. Blayney1, I. Bondarenko2, Y. Shi3, S. Ogenstad4, L. Du5, L. Huang6, R. Mohanlal7 Oncology, Stanford Cancer Institute, Stanford, CA, USA, 2Oncology and Medical Radiology Department, Dnipropetrovsk City Multidisciplinary Clinical Hospital 4, Dnipro, Ukraine, 3Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China, 4Medicine (Oncology), Statogen Consulting, LLC, Zebulon, NC, USA, 5Clinical Operation, Wanchun Bulin Pharmaceuticals Limited, Dalian, China, 6Clinical Operation, BeyondSpring Pharmaceuticals, Inc, New York, NY, USA, 7Clinical Operation, BeyondSpring Pharmaceuticals, New York, NY, USA
Table: 1813P Thrombocytopenia Frequency
T Any Grade T Grade 1 T Grade 2 T Grade 3
Plinþ Peg 0 mg
Plinþ Peg 1.5 mg
Plinþ Peg 3 mg
Plinþ Peg 6 mg
26.7% 20% 6.68% 0%
35.7% 35.7% 0% 0%
52.4% 28.6% 23.8% 0%
93.8% 56.3% 18.8% 18.8%
Peg effect on T P < 0.0001 P ¼ 0.03 P ¼ 0.056 P < 0.01
Conclusions: Plin 20mg/m2 did not induce T. Peg caused a statistically and clinically significant dose-dependent increase in T. A ph III confirmatory trial is underway. Clinical trial identification: BPI-2358-106. Legal entity responsible for the study: BeyondSpring Pharmaceuticals, Inc. Funding: BeyondSpring Pharmaceuticals, Inc. Disclosure: D.W. Blayney: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BeyondSpring Pharmaceuticals, Inc. I. Bondarenko: Honoraria (self): BeyondSpring Pharmaceuticals, Inc. Y. Shi: Honoraria (self), Advisory / Consultancy: BeyondSpring Pharmaceuticals, Inc. S. Ogenstad: Advisory / Consultancy, Travel / Accommodation / Expenses: BeyondSpring Pharmaceuticals, Inc. L. Du: Leadership role, Travel / Accommodation / Expenses, Full / Part-time employment, Officer / Board of Directors: Wanchun Bulin Pharmaceuticals, Inc; Shareholder / Stockholder / Stock options: BeyondSpring, Inc. L. Huang: Leadership role, Travel / Accommodation / Expenses, Full / Part-time employment, Officer / Board of Directors: BeyondSpring Pharmaceuticals, Inc; Shareholder / Stockholder / Stock options: BeyondSpring, Inc. R. Mohanlal: Leadership role, Travel / Accommodation / Expenses, Full / Part-time employment, Officer / Board of Directors: BeyondSpring Pharmaceuticals, Inc; Shareholder / Stockholder / Stock options: BeyondSpring, Inc.
1
Background: Plin is a novel non-G-CSF small molecule, in development for the prevention of Chemo-Induced Neutropenia (CIN) and is differentiated from Peg: Plin has anticancer activity, does not cause bone pain or an immune-suppressive Neutrophil profile (i.e NLR>5; Blayney ASC0 2018, ESMO 2018, SITC 2018). For Intermediate (10-20%) Risk for Febrile Neutropenia (FN) induced by Doc 75mg/m2, single agent (SA) Plin alone was equally effective vs SA Peg standard dose (6mg) for CIN. For High (> 20%) Risk FN induced by TAC, the combination of Plin with Peg 6mg was superior vs SA Peg 6mg, and Plin combined with half-dose Peg (3 mg) was non-inferior, with respect to CIN (Blayney ASCO 2019; St Gallen 2019). Adding Plin to any dose of Peg eradicated Peg-induced bone pain (Blayney St Gallen 2019). Here we evaluated effects of Peg and Plin on absolute platelet count by analyzing thrombocytopenia frequency (T). Methods: We analyzed T Grade (Gr by CTCAE 4.03 criteria) in 4 treatment arms of BC patients receiving 4 cycles of TAC and Peg doses of either 0 mg (N ¼ 15), 1.5 mg (N ¼ 14), 3 mg (N ¼ 21) or 6 mg (N ¼ 16) in the phase (Ph) II Study BPI-2358-106 (NCT03294577). All pts in these 4 arms also received Plin 20 mg/m2. A 5th arm (N ¼ 22) with SA Peg 6mg (without Plin) was also evaluated for T in study 106. Results: Increasing Peg doses caused a statistically significant dose-dependent increase in T (Table below). T frequency with SA Plin was generally low (Table below) and not different from reported T frequency with TAC use (Any Gr T ¼ 39% and Gr3/4 T ¼ 2%; Taxotere Product Label). With SA Peg 6 mg (arm 5), Gr 1 (46%), Gr 2 (5%) and Gr 3 (9%), T was not significantly (P ¼ 0.2) different vs PlinþPeg 6mg. Gr 4 T was not observed.
Volume 30 | Supplement 5 | October 2019
1814P
The use of intravenous ferric carboxymaltose without erythropoiesisstimulating agents in the treatment of anemia in cancer patients undergoing chemotherapy with or without radiotherapy
H. Abdel-Razeq, S.S. Saadeh, R. Malhis, O. AL-Natour, S. Yaser, H. Abdulelah, R. Eljaber, G. Khalaf Internal Medicine, King Hussein Cancer Center KHCC, Amman, Jordan Background: Anemia in cancer patients undergoing chemotherapy is commonly encountered and may worsen their quality of life. Because of recent concerns about their negative effect on overall survival and serious adverse events, erythropoiesis-stimulating agents (ESA) are not commonly prescribed. This study will assess the efficacy and safety of intravenous ferric carboxymaltose (FCM) therapy in such patients. Methods: Adult patients with non-myeloid malignancies on chemotherapy with Hemoglobin (Hb) 11.0 g/dL and a life expectancy >24 weeks were recruited. Based on serum ferritin (sFr) level and transferrin saturation (TSAT), patients were categorized into three Groups: Group-I (Absolute Iron Deficiency: AIDA) with sFr <30 ng/ mL and TSAT <20%. Group-II (Functional Iron Deficiency Anemia: FIDA) with sFr 30-800 ng/mL and TSAT <20%. Patients with TSAT >20% were placed in group-III as “others”. Based on Hb level and body weight, patients were given FCM in one or two short intravenous infusions. Results: A total of 84 patients; 70 (83.3%) females were recruited. Median age [standard deviation] was 53.8 [10.6] years. Chemotherapy varied according to the primary cancer and many had it as a second-line or beyond. The median Hb level at baseline was 10.2 (range: 8.3-11.0 ) gm/dL. At week-12, patients with AIDA (26,31.0%) and FIDA (24, 28.6%) had a significant increment in Hb (median increment: 2.35 and 1.5 gm/dL, respectively). Patients in Group-III (34, 40.5%) had limited response. Most of the increment (1.0 g/dL) occurred as early as week-3. No immediate infusion-related adverse events were reported. However, asymptomatic hypophosphatemia was observed in 39 (46.4%) patients (table). Conclusions: Intravenous FCM, without ESA, is safe and effective in the treatment of anemia in cancer patients undergoing active treatment with chemotherapy. Legal entity responsible for the study: The authors. Funding: King Hussein Cancer Center. Disclosure: All authors have declared no conflicts of interest.
doi:10.1093/annonc/mdz265 | v737
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Results: A total of 1080 pts were enrolled, of which 953 were included in the full analysis set: 144 had lymphoma (DLBCL, N ¼ 39; Hodgkin’s lymphoma, N ¼ 105), and 809 had solid tumours (breast, N ¼ 299; lung, N ¼ 144; gastrointestinal [GI], N ¼ 366 [colorectal, N ¼ 203; pancreatic, N ¼ 106; gastric N ¼ 39; oesophageal, N ¼ 18]). The Table shows modalities of filgrastim treatment for pts receiving chemotherapy for curative intent. Similar results were reported in pts receiving chemotherapy for palliative intent. Pts with solid tumours were planned to receive filgrastim on Day 2 of treatment for 5 days duration. Pts with lymphoma were planned to receive filgrastim on Day 3 for 4– 8 days duration. Of the patients receiving chemotherapy for curative intent, FN was reported in 2 pts with GI cancer, 1 pt with lung cancer and 7 pts with lymphoma. Conclusions: Biosimilar filgrastim treatment in pts receiving chemotherapy with a rest period of 14 days results in a low incidence of FN in real-world clinical practice. Editorial acknowledgement: Caroline McGown of Spirit Medical Communications Ltd, supported by Sandoz. Legal entity responsible for the study: Sandoz. Funding: Sandoz. Disclosure: J.M. Phelip: Advisory / Consultancy: Roche; Advisory / Consultancy: Merck; Advisory /
abstracts
Annals of Oncology
Table: 1814P Variables
Absolute iron deficiency (n ¼ 26)
Functional iron deficiency (n ¼ 24)
Others (n ¼ 34)
P-value
Ferritin Level (week 12, mg/mL) Mean (SD) Median (range) Phophorus level (week 2, mg/dL) Mean (SD) Median (range) Hypophophatemia Number Percentage
589 (509) 442 (177-2794) 1.8 (0.7) 1.5 (1.1-3.4) 17 65.4%
838 (875) 577 (168-4184) 2.5 (1.0) 3.3 (1.0-5.4) 6 25.0%
956 (667) 802 (166-2687) 2.2 (0.9) 3.3 (1.0-4.1) 16 47.1%
0.0247 0.0124
Randomized, double-blind, cross-over phase I study comparing pharmacokinetics, pharmacodynamics, safety and immunogenicity of a biosimilar pegfilgrastim with EU and US references
M. Velinova1, A. Bellon2, R. Nakov2, S. Schussler3, S. Schier-Mumzhiu2, C. Schelcher2, S.D. Koch2, A. Skerjanec4, J. Wang5, A. Krendyukov6, G.P. Otto2 1 PRA Health Science, Groningen, Netherlands, 2Clinical Development, Hexal AG, Holzkirchen, Germany, 3Clinical Development, Sandoz Inc., Princeton, NJ, USA, 4Clinical Development, Novartis AG, Basel, Switzerland, 5Biostatistics, Sandoz Inc., Princeton, NJ, USA, 6Medical Affairs, Hexal AG, Holzkirchen, Germany Background: The pharmacokinetic (PK)/pharmacodynamic (PD), safety and immuR ) and EU reference nogenicity profiles of Sandoz biosimilar pegfilgrastim (ZiextenzoV pegfilgrastim were shown to be similar in a pivotal phase I study. Similarity of efficacy and safety to the reference was demonstrated in two phase III studies in breast cancer patients receiving myelosuppressive chemotherapy. This 3-way study aimed to confirm similarity of PK/PD, safety and immunogenicity to US reference pegfilgrastim, and to bridge between the EU and US reference medicines. Methods: This randomized, double-blind, 3-treatment, 6-sequence crossover phase I study included healthy volunteers (HVs) administered pegfilgrastim (biosimilar, EU reference, or US reference) once per treatment period. Primary objectives were to demonstrate PK similarity in AUC0-inf, AUC0-last and Cmax, and PD similarity in ANC AUEC0-last and ANC Emax. The study was powered (90%) to achieve confidence intervals within biosimilarity margins 0.8–1.25 in pairwise comparisons (biosimilar vs US reference, biosimilar vs EU reference, and US reference vs EU reference). Secondary objectives were safety, immunogenicity and additional PK/PD parameters. Results: The study included 577 male and female HVs. PK and PD similarity were demonstrated for primary PK and PD parameters between Sandoz biosimilar, US reference, and EU reference (Table). The safety profile of Sandoz biosimilar pegfilgrastim was similar across groups. Incidence of antidrug antibodies was similar across groups (biosimilar: 31/512 [6.1%]; US reference: 36/511 [7.0%]; EU reference: 39/501 [7.8%]). Secondary PK/PD parameters were also similar. Conclusions: Sandoz biosimilar demonstrated similar PK/PD, safety, tolerability and immunogenicity to US reference and EU reference pegfilgrastim in this large 3-way crossover phase I study.
Table: 1815P Summary of PK and PD similarity
Biosimilar / US-reference Biosimilar / EU-reference US-reference / EU-reference
AUC0-last AUEC0-last AUC0-last AUEC0-last AUC0-last AUEC0-last
Ratio
CI 90%
1.0635 0.9997 1.0469 1.0012 0.9844 1.0015
1.0087, 1.1213 0.9912, 1.0082 0.9929, 1.1038 0.9927, 1.0098 0.9336, 1.0380 0.9930, 1.0101
Clinical trial identification: EudraCT: 2016-003549-27. Editorial acknowledgement: Caroline McGown of Spirit Medical Communications Ltd, supported by Hexal AG. Legal entity responsible for the study: Hexal AG. Funding: Hexal AG. Disclosure: M. Velinova: Full / Part-time employment: PRA; Honoraria (self), compensation as lead Principal Investigator in the study: Sandoz Biopharmaceuticals. A. Bellon: Full / Part-time employment: Hexal AG. R. Nakov: Full / Part-time employment: Hexal AG. S. Schussler: Full / Parttime employment: Sandoz Inc. S. Schier-Mumzhiu: Full / Part-time employment: Hexal AG. C. Schelcher: Full / Part-time employment: Hexal AG. S.D. Koch: Full / Part-time employment: Hexal AG. A. Skerjanec: Full / Part-time employment: Novartis. J. Wang: Full / Part-time employment: Sandoz Inc. A. Krendyukov: Full / Part-time employment: Hexal AG. G.P. Otto: Full / Part-time employment: Hexal AG.
v738 | Supportive Care
1816P
Prophylaxis with lipegfilgrastim in patients with primary breast cancer receiving dose dense chemotherapy: Results from the German NIS NADENS
M. Kiechle1, C. Schem2, D. Lu¨ftner3, X. Hamann4, R. Ju¨nemann4, M. To¨lg5, U. Ko¨hler6 Frauenklinik, Rechts der Isar Hospital, TUM, Munich, Germany, 2Mammazentrum/Op. Therapie und Onkologie, Krankenhaus Jerusalem, Hamburg, Schleswig-Holstein, Germany, 3Medizinische Klinik III, Charite, Campus Benjamin Franklin, Berlin, Germany, 4 Medical Affairs, Teva GmbH, Ulm, Germany, 5Mediveritas GmbH, Munich, Germany, 6 Klinik fu¨r Gyn€ akologie und Geburtshilfe, Klinikum St. Georg, Leipzig, Germany
1
Background: Only limited data are available on the impact of primary prophylactic use of G-CSF in high risk breast cancer (BC) patients (pts) treated with dose dense (dd) chemotherapy (CTx) protocols in standard clinical practice. Lipegfilgrastim (LF) is a glyco-pegylated long-acting G-CSF indicated to reduce the duration of neutropenia and the incidence of febrile neutropenia (FN). Methods: NADENS was a multi-center, prospective, non-interventional study (NIS) in Germany on the primary prophylactic LF administration for BC pts treated with dd two-weekly CTx. 328 pts were enrolled at 68 sites (27 hospitals with 143 pts, 41 private practices with 185 pts, Safety Set (SAF)). Due to protocol violations 46 pts were excluded from analysis set (282 pts). Results: Severe neutropenia (SN, grade 3/4) occurred in 131 pts (46.5%) at least once during max. 4 observed cycles. Incidences in cycles 1/2/3/4 were 33.3%/22.1%/22.9%/ 19.8%, respectively. 6 pts (2.1%) experienced a FN, (incidence per cycle 1.1%/0.4%/ 1.4%/0.4%). Altogether 275 SN and 9 FN events were documented for the 1,121 observed CTx cycles. CTx had to be modified in 74 pts (26.2%). 96 pts (34.0%) received anti-infectives. 35 pts were hospitalized (12.4%) with 51 single hospitalizations. Reasons included FN (4 events), other neutropenic complications (5) and infections (7). No stay on ICU was reported. AEs were observed for 119 pts (36.3% of SAF, 342 events) and SAEs for 23 pts (7.0%, 30 events). No AE was fatal, 12 AEs (3.6%) were rated as grade 4. 89 AEs (in 61 pts) were classified as probable or possible drug related. For 280 pts (99.3%) treatment with LF was rated as ‘beneficial’ by the treating physician. Tolerability of LF treatment was assessed mostly as ’very good’ (152 pts, 53.9%) or ’good’ (120 pts, 42.6%), ’moderate’ was documented for 8 pts (2.8%), ’bad’ for 2 pts (0.7%). Conclusions: NADENS provides a realistic picture about the use and efficacy of LF for this defined patient group in daily clinical care in Germany. LF was found to be effective and safe and results fall in the range of those observed in RCTs. No new safety signal was detected. The known limitations of non-interventional studies have to be considered. Clinical trial identification: XM22-ONC-40115 (BfArM NIS No 7038). Legal entity responsible for the study: Teva GmbH, Ulm, Germany. Funding: Teva GmbH, Ulm, Germany. Disclosure: M. Kiechle: Advisory / Consultancy: Teva GmbH. C. Schem: Advisory / Consultancy, Speaker Bureau / Expert testimony: Teva GmbH. D. Lu¨ftner: Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Teva GmbH; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Amgen; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: AstraZeneca; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Celgene; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Lilly; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Loreal; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: MSD; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Mundipharma; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Mylan; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Novartis; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Pfizer; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Roche; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Tesaro. X. Hamann: Full / Parttime employment: Teva GmbH. R. Ju¨nemann: Full / Part-time employment: Teva GmbH. M. To¨lg: Honoraria (institution), CRO for reported study: Teva GmbH. U. Ko¨hler: Advisory / Consultancy: Teva GmbH.
Volume 30 | Supplement 5 | October 2019
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1815P
Annals of Oncology
Consultancy: Amgen; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Bayer; Advisory / Consultancy: Servier; Advisory / Consultancy: Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Pierre Favre; Research grant / Funding (institution): Merck Serono. P. Souquet: Honoraria (self), Speaker Bureau / Expert testimony, Non-remunerated activity/ies: Sandoz (a Novartis company). M. Declerck: Full / Part-time employment: Sandoz. E. Nabirotchkina: Full / Parttime employment: Sandoz. O. Tredan: Non-remunerated activity/ies: Sandoz; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Lilly; Honoraria (self): Astra-Zeneca; Honoraria (self): MSD-Merck; Honoraria (self): BMS. All other authors have declared no conflicts of interest.
1813P
The effect of increasing doses of pegfilgrastim (Peg) on thrombocytopenia (T) in breast cancer (BC) patients (pts) receiving taxotere (Doc), doxorubicin, cyclophosphamide (TAC) and plinabulin (Plin)
D.W. Blayney1, I. Bondarenko2, Y. Shi3, S. Ogenstad4, L. Du5, L. Huang6, R. Mohanlal7 Oncology, Stanford Cancer Institute, Stanford, CA, USA, 2Oncology and Medical Radiology Department, Dnipropetrovsk City Multidisciplinary Clinical Hospital 4, Dnipro, Ukraine, 3Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China, 4Medicine (Oncology), Statogen Consulting, LLC, Zebulon, NC, USA, 5Clinical Operation, Wanchun Bulin Pharmaceuticals Limited, Dalian, China, 6Clinical Operation, BeyondSpring Pharmaceuticals, Inc, New York, NY, USA, 7Clinical Operation, BeyondSpring Pharmaceuticals, New York, NY, USA
Table: 1813P Thrombocytopenia Frequency
T Any Grade T Grade 1 T Grade 2 T Grade 3
Plinþ Peg 0 mg
Plinþ Peg 1.5 mg
Plinþ Peg 3 mg
Plinþ Peg 6 mg
26.7% 20% 6.68% 0%
35.7% 35.7% 0% 0%
52.4% 28.6% 23.8% 0%
93.8% 56.3% 18.8% 18.8%
Peg effect on T P < 0.0001 P ¼ 0.03 P ¼ 0.056 P < 0.01
Conclusions: Plin 20mg/m2 did not induce T. Peg caused a statistically and clinically significant dose-dependent increase in T. A ph III confirmatory trial is underway. Clinical trial identification: BPI-2358-106. Legal entity responsible for the study: BeyondSpring Pharmaceuticals, Inc. Funding: BeyondSpring Pharmaceuticals, Inc. Disclosure: D.W. Blayney: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BeyondSpring Pharmaceuticals, Inc. I. Bondarenko: Honoraria (self): BeyondSpring Pharmaceuticals, Inc. Y. Shi: Honoraria (self), Advisory / Consultancy: BeyondSpring Pharmaceuticals, Inc. S. Ogenstad: Advisory / Consultancy, Travel / Accommodation / Expenses: BeyondSpring Pharmaceuticals, Inc. L. Du: Leadership role, Travel / Accommodation / Expenses, Full / Part-time employment, Officer / Board of Directors: Wanchun Bulin Pharmaceuticals, Inc; Shareholder / Stockholder / Stock options: BeyondSpring, Inc. L. Huang: Leadership role, Travel / Accommodation / Expenses, Full / Part-time employment, Officer / Board of Directors: BeyondSpring Pharmaceuticals, Inc; Shareholder / Stockholder / Stock options: BeyondSpring, Inc. R. Mohanlal: Leadership role, Travel / Accommodation / Expenses, Full / Part-time employment, Officer / Board of Directors: BeyondSpring Pharmaceuticals, Inc; Shareholder / Stockholder / Stock options: BeyondSpring, Inc.
1
Background: Plin is a novel non-G-CSF small molecule, in development for the prevention of Chemo-Induced Neutropenia (CIN) and is differentiated from Peg: Plin has anticancer activity, does not cause bone pain or an immune-suppressive Neutrophil profile (i.e NLR>5; Blayney ASC0 2018, ESMO 2018, SITC 2018). For Intermediate (10-20%) Risk for Febrile Neutropenia (FN) induced by Doc 75mg/m2, single agent (SA) Plin alone was equally effective vs SA Peg standard dose (6mg) for CIN. For High (> 20%) Risk FN induced by TAC, the combination of Plin with Peg 6mg was superior vs SA Peg 6mg, and Plin combined with half-dose Peg (3 mg) was non-inferior, with respect to CIN (Blayney ASCO 2019; St Gallen 2019). Adding Plin to any dose of Peg eradicated Peg-induced bone pain (Blayney St Gallen 2019). Here we evaluated effects of Peg and Plin on absolute platelet count by analyzing thrombocytopenia frequency (T). Methods: We analyzed T Grade (Gr by CTCAE 4.03 criteria) in 4 treatment arms of BC patients receiving 4 cycles of TAC and Peg doses of either 0 mg (N ¼ 15), 1.5 mg (N ¼ 14), 3 mg (N ¼ 21) or 6 mg (N ¼ 16) in the phase (Ph) II Study BPI-2358-106 (NCT03294577). All pts in these 4 arms also received Plin 20 mg/m2. A 5th arm (N ¼ 22) with SA Peg 6mg (without Plin) was also evaluated for T in study 106. Results: Increasing Peg doses caused a statistically significant dose-dependent increase in T (Table below). T frequency with SA Plin was generally low (Table below) and not different from reported T frequency with TAC use (Any Gr T ¼ 39% and Gr3/4 T ¼ 2%; Taxotere Product Label). With SA Peg 6 mg (arm 5), Gr 1 (46%), Gr 2 (5%) and Gr 3 (9%), T was not significantly (P ¼ 0.2) different vs PlinþPeg 6mg. Gr 4 T was not observed.
Volume 30 | Supplement 5 | October 2019
1814P
The use of intravenous ferric carboxymaltose without erythropoiesisstimulating agents in the treatment of anemia in cancer patients undergoing chemotherapy with or without radiotherapy
H. Abdel-Razeq, S.S. Saadeh, R. Malhis, O. AL-Natour, S. Yaser, H. Abdulelah, R. Eljaber, G. Khalaf Internal Medicine, King Hussein Cancer Center KHCC, Amman, Jordan Background: Anemia in cancer patients undergoing chemotherapy is commonly encountered and may worsen their quality of life. Because of recent concerns about their negative effect on overall survival and serious adverse events, erythropoiesis-stimulating agents (ESA) are not commonly prescribed. This study will assess the efficacy and safety of intravenous ferric carboxymaltose (FCM) therapy in such patients. Methods: Adult patients with non-myeloid malignancies on chemotherapy with Hemoglobin (Hb) 11.0 g/dL and a life expectancy >24 weeks were recruited. Based on serum ferritin (sFr) level and transferrin saturation (TSAT), patients were categorized into three Groups: Group-I (Absolute Iron Deficiency: AIDA) with sFr <30 ng/ mL and TSAT <20%. Group-II (Functional Iron Deficiency Anemia: FIDA) with sFr 30-800 ng/mL and TSAT <20%. Patients with TSAT >20% were placed in group-III as “others”. Based on Hb level and body weight, patients were given FCM in one or two short intravenous infusions. Results: A total of 84 patients; 70 (83.3%) females were recruited. Median age [standard deviation] was 53.8 [10.6] years. Chemotherapy varied according to the primary cancer and many had it as a second-line or beyond. The median Hb level at baseline was 10.2 (range: 8.3-11.0 ) gm/dL. At week-12, patients with AIDA (26,31.0%) and FIDA (24, 28.6%) had a significant increment in Hb (median increment: 2.35 and 1.5 gm/dL, respectively). Patients in Group-III (34, 40.5%) had limited response. Most of the increment (1.0 g/dL) occurred as early as week-3. No immediate infusion-related adverse events were reported. However, asymptomatic hypophosphatemia was observed in 39 (46.4%) patients (table). Conclusions: Intravenous FCM, without ESA, is safe and effective in the treatment of anemia in cancer patients undergoing active treatment with chemotherapy. Legal entity responsible for the study: The authors. Funding: King Hussein Cancer Center. Disclosure: All authors have declared no conflicts of interest.
doi:10.1093/annonc/mdz265 | v737
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Results: A total of 1080 pts were enrolled, of which 953 were included in the full analysis set: 144 had lymphoma (DLBCL, N ¼ 39; Hodgkin’s lymphoma, N ¼ 105), and 809 had solid tumours (breast, N ¼ 299; lung, N ¼ 144; gastrointestinal [GI], N ¼ 366 [colorectal, N ¼ 203; pancreatic, N ¼ 106; gastric N ¼ 39; oesophageal, N ¼ 18]). The Table shows modalities of filgrastim treatment for pts receiving chemotherapy for curative intent. Similar results were reported in pts receiving chemotherapy for palliative intent. Pts with solid tumours were planned to receive filgrastim on Day 2 of treatment for 5 days duration. Pts with lymphoma were planned to receive filgrastim on Day 3 for 4– 8 days duration. Of the patients receiving chemotherapy for curative intent, FN was reported in 2 pts with GI cancer, 1 pt with lung cancer and 7 pts with lymphoma. Conclusions: Biosimilar filgrastim treatment in pts receiving chemotherapy with a rest period of 14 days results in a low incidence of FN in real-world clinical practice. Editorial acknowledgement: Caroline McGown of Spirit Medical Communications Ltd, supported by Sandoz. Legal entity responsible for the study: Sandoz. Funding: Sandoz. Disclosure: J.M. Phelip: Advisory / Consultancy: Roche; Advisory / Consultancy: Merck; Advisory /
abstracts
Annals of Oncology
Table: 1814P Variables
Absolute iron deficiency (n ¼ 26)
Functional iron deficiency (n ¼ 24)
Others (n ¼ 34)
P-value
Ferritin Level (week 12, mg/mL) Mean (SD) Median (range) Phophorus level (week 2, mg/dL) Mean (SD) Median (range) Hypophophatemia Number Percentage
589 (509) 442 (177-2794) 1.8 (0.7) 1.5 (1.1-3.4) 17 65.4%
838 (875) 577 (168-4184) 2.5 (1.0) 3.3 (1.0-5.4) 6 25.0%
956 (667) 802 (166-2687) 2.2 (0.9) 3.3 (1.0-4.1) 16 47.1%
0.0247 0.0124
Randomized, double-blind, cross-over phase I study comparing pharmacokinetics, pharmacodynamics, safety and immunogenicity of a biosimilar pegfilgrastim with EU and US references
M. Velinova1, A. Bellon2, R. Nakov2, S. Schussler3, S. Schier-Mumzhiu2, C. Schelcher2, S.D. Koch2, A. Skerjanec4, J. Wang5, A. Krendyukov6, G.P. Otto2 1 PRA Health Science, Groningen, Netherlands, 2Clinical Development, Hexal AG, Holzkirchen, Germany, 3Clinical Development, Sandoz Inc., Princeton, NJ, USA, 4Clinical Development, Novartis AG, Basel, Switzerland, 5Biostatistics, Sandoz Inc., Princeton, NJ, USA, 6Medical Affairs, Hexal AG, Holzkirchen, Germany Background: The pharmacokinetic (PK)/pharmacodynamic (PD), safety and immuR ) and EU reference nogenicity profiles of Sandoz biosimilar pegfilgrastim (ZiextenzoV pegfilgrastim were shown to be similar in a pivotal phase I study. Similarity of efficacy and safety to the reference was demonstrated in two phase III studies in breast cancer patients receiving myelosuppressive chemotherapy. This 3-way study aimed to confirm similarity of PK/PD, safety and immunogenicity to US reference pegfilgrastim, and to bridge between the EU and US reference medicines. Methods: This randomized, double-blind, 3-treatment, 6-sequence crossover phase I study included healthy volunteers (HVs) administered pegfilgrastim (biosimilar, EU reference, or US reference) once per treatment period. Primary objectives were to demonstrate PK similarity in AUC0-inf, AUC0-last and Cmax, and PD similarity in ANC AUEC0-last and ANC Emax. The study was powered (90%) to achieve confidence intervals within biosimilarity margins 0.8–1.25 in pairwise comparisons (biosimilar vs US reference, biosimilar vs EU reference, and US reference vs EU reference). Secondary objectives were safety, immunogenicity and additional PK/PD parameters. Results: The study included 577 male and female HVs. PK and PD similarity were demonstrated for primary PK and PD parameters between Sandoz biosimilar, US reference, and EU reference (Table). The safety profile of Sandoz biosimilar pegfilgrastim was similar across groups. Incidence of antidrug antibodies was similar across groups (biosimilar: 31/512 [6.1%]; US reference: 36/511 [7.0%]; EU reference: 39/501 [7.8%]). Secondary PK/PD parameters were also similar. Conclusions: Sandoz biosimilar demonstrated similar PK/PD, safety, tolerability and immunogenicity to US reference and EU reference pegfilgrastim in this large 3-way crossover phase I study.
Table: 1815P Summary of PK and PD similarity
Biosimilar / US-reference Biosimilar / EU-reference US-reference / EU-reference
AUC0-last AUEC0-last AUC0-last AUEC0-last AUC0-last AUEC0-last
Ratio
CI 90%
1.0635 0.9997 1.0469 1.0012 0.9844 1.0015
1.0087, 1.1213 0.9912, 1.0082 0.9929, 1.1038 0.9927, 1.0098 0.9336, 1.0380 0.9930, 1.0101
Clinical trial identification: EudraCT: 2016-003549-27. Editorial acknowledgement: Caroline McGown of Spirit Medical Communications Ltd, supported by Hexal AG. Legal entity responsible for the study: Hexal AG. Funding: Hexal AG. Disclosure: M. Velinova: Full / Part-time employment: PRA; Honoraria (self), compensation as lead Principal Investigator in the study: Sandoz Biopharmaceuticals. A. Bellon: Full / Part-time employment: Hexal AG. R. Nakov: Full / Part-time employment: Hexal AG. S. Schussler: Full / Parttime employment: Sandoz Inc. S. Schier-Mumzhiu: Full / Part-time employment: Hexal AG. C. Schelcher: Full / Part-time employment: Hexal AG. S.D. Koch: Full / Part-time employment: Hexal AG. A. Skerjanec: Full / Part-time employment: Novartis. J. Wang: Full / Part-time employment: Sandoz Inc. A. Krendyukov: Full / Part-time employment: Hexal AG. G.P. Otto: Full / Part-time employment: Hexal AG.
v738 | Supportive Care
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Prophylaxis with lipegfilgrastim in patients with primary breast cancer receiving dose dense chemotherapy: Results from the German NIS NADENS
M. Kiechle1, C. Schem2, D. Lu¨ftner3, X. Hamann4, R. Ju¨nemann4, M. To¨lg5, U. Ko¨hler6 Frauenklinik, Rechts der Isar Hospital, TUM, Munich, Germany, 2Mammazentrum/Op. Therapie und Onkologie, Krankenhaus Jerusalem, Hamburg, Schleswig-Holstein, Germany, 3Medizinische Klinik III, Charite, Campus Benjamin Franklin, Berlin, Germany, 4 Medical Affairs, Teva GmbH, Ulm, Germany, 5Mediveritas GmbH, Munich, Germany, 6 Klinik fu¨r Gyn€ akologie und Geburtshilfe, Klinikum St. Georg, Leipzig, Germany
1
Background: Only limited data are available on the impact of primary prophylactic use of G-CSF in high risk breast cancer (BC) patients (pts) treated with dose dense (dd) chemotherapy (CTx) protocols in standard clinical practice. Lipegfilgrastim (LF) is a glyco-pegylated long-acting G-CSF indicated to reduce the duration of neutropenia and the incidence of febrile neutropenia (FN). Methods: NADENS was a multi-center, prospective, non-interventional study (NIS) in Germany on the primary prophylactic LF administration for BC pts treated with dd two-weekly CTx. 328 pts were enrolled at 68 sites (27 hospitals with 143 pts, 41 private practices with 185 pts, Safety Set (SAF)). Due to protocol violations 46 pts were excluded from analysis set (282 pts). Results: Severe neutropenia (SN, grade 3/4) occurred in 131 pts (46.5%) at least once during max. 4 observed cycles. Incidences in cycles 1/2/3/4 were 33.3%/22.1%/22.9%/ 19.8%, respectively. 6 pts (2.1%) experienced a FN, (incidence per cycle 1.1%/0.4%/ 1.4%/0.4%). Altogether 275 SN and 9 FN events were documented for the 1,121 observed CTx cycles. CTx had to be modified in 74 pts (26.2%). 96 pts (34.0%) received anti-infectives. 35 pts were hospitalized (12.4%) with 51 single hospitalizations. Reasons included FN (4 events), other neutropenic complications (5) and infections (7). No stay on ICU was reported. AEs were observed for 119 pts (36.3% of SAF, 342 events) and SAEs for 23 pts (7.0%, 30 events). No AE was fatal, 12 AEs (3.6%) were rated as grade 4. 89 AEs (in 61 pts) were classified as probable or possible drug related. For 280 pts (99.3%) treatment with LF was rated as ‘beneficial’ by the treating physician. Tolerability of LF treatment was assessed mostly as ’very good’ (152 pts, 53.9%) or ’good’ (120 pts, 42.6%), ’moderate’ was documented for 8 pts (2.8%), ’bad’ for 2 pts (0.7%). Conclusions: NADENS provides a realistic picture about the use and efficacy of LF for this defined patient group in daily clinical care in Germany. LF was found to be effective and safe and results fall in the range of those observed in RCTs. No new safety signal was detected. The known limitations of non-interventional studies have to be considered. Clinical trial identification: XM22-ONC-40115 (BfArM NIS No 7038). Legal entity responsible for the study: Teva GmbH, Ulm, Germany. Funding: Teva GmbH, Ulm, Germany. Disclosure: M. Kiechle: Advisory / Consultancy: Teva GmbH. C. Schem: Advisory / Consultancy, Speaker Bureau / Expert testimony: Teva GmbH. D. Lu¨ftner: Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Teva GmbH; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Amgen; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: AstraZeneca; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Celgene; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Lilly; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Loreal; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: MSD; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Mundipharma; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Mylan; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Novartis; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Pfizer; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Roche; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Tesaro. X. Hamann: Full / Parttime employment: Teva GmbH. R. Ju¨nemann: Full / Part-time employment: Teva GmbH. M. To¨lg: Honoraria (institution), CRO for reported study: Teva GmbH. U. Ko¨hler: Advisory / Consultancy: Teva GmbH.
Volume 30 | Supplement 5 | October 2019
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