SURVEY SUL CONFLITTO DI INTERESSE IN ONCOLOGIA PROMOSSO DAL CIPOMO 1-31 MARZO. PARTECIPATE TUTTI nicsonet.it

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1 SURVEY SUL CONFLITTO DI INTERESSE IN ONCOLOGIA PROMOSSO DAL CIPOMO 1-31 MARZO PARTECIPATE TUTTI nicsonet.it

2 LINEE GUIDA AIOM: LA TERAPIA ANTIEMETICA Fausto Roila S.C. Oncologia Medica, Terni

3 CONFLICT OF INTEREST: DISCLOSURE No conflict of interest

4 Coordinatore Fausto Roila AIOM Oncologia Medica - A.O. S.Maria - Terni Segretario Lucia Mentuccia AIOM Oncologia Medica - Ospedale SS Trinità - Sora (FR) Estensori Claudia Caserta AIOM Oncologia - A.O. Santa Maria - Terni Sonia Fatigoni Oncologia - A.O. Santa Maria - Terni evisori Silvana Chiara AIOM Oncologia Medica - A.O.U. San Martino-IST - Genova Alessandra Fabi AIOM Oncologia Medica I - I.F.O. Regina Elena - Roma Maria Cristina Locatelli AIOM Oncologia Medica - A.O. S.Carlo Borromeo - Milano Ernesto Maranzano AIRO Radioterapia oncologica - A.O. Santa Maria - Terni Mimma Raffaele AIOM Oncologia - Inrca-Ist.naz.rip.e Cura Anziani - Roma

5 EMETOGENIC POTENTIAL OF SINGLE INTRAVENOUS CHEMOTHERAPY AGENTS EMETIC RISK AGENT HIGH Cisplatin Mechlorethamine Streptozocin Cyclophosphamide > 1500 mg/m 2 Carmustine Dacarbazine AC or EC regimens (breast cancer pts)

6 ANTIEMETICS FOR THE PREVENTION OF CISPLATIN-INDUCED ACUTE AND DELAYED EMESIS

7 TWO RCT ON APREPITANT (2003) day 1 days 2-3 day 4 Aprepitant 125 mg 80 mg - Ondansetron 32 mg - - Dexamethasone 12 mg 8 mg 8 mg Ondansetron 32 mg - - Dexamethasone 20 mg 8 mg bid 8 mg bid Aprepitant p.o. Ondansetron i.v. Dexamethasone p.o.

8 RESULTS Protocol 052 Protocol 054 AOD OD AOD OD No. pts Complete response (%) Day % % Day % % no nausea (%)

9 MASCC/ESMO 2010 RECOMMENDATIONS ON ANTIEMETIC PROPHYLAXIS ACUTE DELAYED Cisplatin 5HT3+DEX+Apr DEX+Apr

10 SINGLE-DOSE FOSAPREPITANT FOR THE PREVENTION OF CHEMOTHERAPY- INDUCED NAUSEA AND VOMITING ASSOCIATED WITH CISPLATIN THERAPY: RANDOMIZED, DOUBLE-BLIND STUDY PROTOCOL EASE Grunberg S, et al. J Clin Oncol 2011; 29:

11 STUDY DESIGN (2247 pts) D1 D2 D3 D4 Aprepitant po 125 mg 80 mg 80 mg - Ondansetron 32 mg Dexamethasone 12 mg 8 mg 8 mg 8mg Fosaprepitant iv 150 mg Ondansetron 32 mg Dexamethasone 12 mg 8mg 8 mg bid 8 mg bid ondansetron iv desametasone po

12 RESULTS (% COMPLETE RESPONSE) FOD AOD p day n.s. days n.s. days n.s.

13 Efficacy and safety of NEPA, an oral combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy: a randomized doseranging pivotal study Hesketh PJ, et al. Ann Oncol 2014; 25:

14 DESIGN OF THE STUDY (694 pts) D1 D2-3 D4 PALO Palo 0.50mg+ Dex 8 mg bid Dex 8 mg bid Dex 20 mg po NEPA100 NEPA200 NEPA300 netu100 +Palo Dex 4 mg bid Dex 4 mg bid + Dex 12 mg po netu200 +Palo Dex 4 mg bid Dex 4 mg bid + Dex 12 mg po netu300 +Palo Dex 4 mg bid Dex 4 mg bid + Dex 12 mg po APR+OND apr 125mg + Apr 80mg + Dex 4 mg bid OND 32mg iv + Dex 4 mg bid Dex 12 mg po

15 RESULTS (% COMPLETE RESPONSE) D1-D5 D1 D2-D5 PALO NEPA * * NEPA * * NEPA * 98.5* 90.4* APR+OND * 88.8* * Statistically significant with respect to PALO

16 Safety and efficacy of rolapitant, for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: two randomised, active-controlled, double-blind, phase III trials Rapoport BL, et al. Lancet Oncol 2015; 16:

17 STUDY DESIGN D1 D2-3 D4 Rolapitant 200 mg - - Granisetron 10 µg/kg - - Dexamethasone 20 mg 8 mg bid 8 mg bid Granisetron 10 µg/kg - - Dexamethasone 20 mg 8 mg bid 8 mg bid Rolapitant po Granisetron iv Dexamethasone po

18 RESULTS (555 pts) RGD GD P Day % 79.5 n.s. Day % Day n.s. no nausea (%)

19 RESULTS (532 pts) RGD GD P Day % Day % 58.4 <0.001 Day <0.001

20 CONCLUSIONS - The addition of an NK1 receptor antagonists in pts submitted to cisplatin chemotherapy increased the complete response on day 1 from 4% to 15% and on days 2-5 from 8% to 21%. - Part of this increase is due to a dependence effect (the better results achieved on the day 1 which induced an increase of the complete responses on days 2-5)

21 APREPITANT VERSUS METOCLOPRAMIDE, BOTH COMBINED WITH DEXAMETHASONE, FOR THE PREVENTION OF CISPLATIN- INDUCED DELAYED EMESIS: A RANDOMIZED, DOUBLE-BLIND STUDY Roila F, et al. Ann Oncol 2015; 26:

22 METHODS STUDY DESIGN - A randomized double-blind study comparing aprepitant versus metoclopramide, both combined with dexamethasone, was carried out in naive cancer pts treated with cisplatin-based chemotherapy. -Before chemotherapy, all patients were treated with intravenous palonosetron 0.25 mg and dexamethasone 12 mg and oral aprepitant 125 mg ANTIEMETIC TREATMENTS -Oral dexamethasone 8 mg once daily on days 2-4 plus aprepitant 80 mg daily on days 2-3 -Oral dexamethasone 8 mg bid on days 2-4 plus metoclopramide 20 mg 4 times daily on days 2-4

23 RESULTS IN THE DELAYED PHASE (284 pts) MTC + DEX APR + DEX No. of patients (%) 137 (%) 147 (%) RESPONSES complete response 113 (82.5) 118 (80.3) n.s. complete protection 102 (74.5) 108 (73.5) n.s. total control 97 (70.8) 102 (69.4) n.s. no vomiting 120 (87.6) 129 (87.8) n.s. no nausea 100 (73.0) 105 (71.4) n.s. no significant nausea 111 (81.0) 114 (77.6) n.s. (VAS < 25 mm) mean number of emetic episodes (sd) 7.9 (7.4) 8.4 (11.8) n.s. mean maximum severity of nausea (sd) 44.8 (25.5) 44.9 (26.2) n.s. mean duration of nausea, hours (sd) 13.5 (16.5) 15.4 (19.0) n.s. p

24 CONCLUSIONS - Recently EMA reduced the dose and the duration of the antiemetic treatment with oral metoclopramide to 10 mg TID for maximum 1 week (risk of neurological side effects such as short-term extrapyramidal disorders). Therefore, our metoclopramide regimen is not utilizable in the clinical practice.

25 MASCC/ESMO 2016 RECOMMENDATIONS ACUTE DELAYED Cisplatin 5HT3+DEX+NK1 DEX 5HT3+DEX+APR DEX+APR or MTC

26 ANTIEMETICS FOR THE PREVENTION OF ACUTE AND DELAYED EMESIS INDUCED BY AC/EC REGIMENS

27 MASCC/ESMO 2010 RECOMMENDATIONS ACUTE DELAYED AC 5HT3+DEX+Apr Apr

28 Breast cancer pts treated with CTX ± DOX or EPI (2005) D1 D2-3 Aprepitant 125 mg 80 mg Ondansetron 8/8 mg - Desametasone 12 mg - Ondansetron 8/8 mg 8/8 mg Dexamethasone 20 mg - Aprepitant po Ondansetron po Dexamethasone po

29 RESULTS* AOD OD P No. pts Day Day % Day % No nausea days n.s. *Complete response: no vomiting and no rescue therapy

30 A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy Aapro M, et al. Ann Oncol 2014; 25:

31 DESIGN OF THE STUDY (1455 pts) Double-blind, randomized study in chemotherapy-naive patients undergoing anthracycline-cyclophosphamide chemotherapy submitted to: - oral NEPA + oral dexamethasone 12 mg (NEPA= NETU 300 mg + PALO 0.50 mg) - oral PALO 0.50 mg + oral dexamethasone 20 mg Primary endpoint: complete response during delayed phase

32 RESULTS (% COMPLETE RESPONSE) D2-D5 D1 D1-D5 PALO + DEX % % 66.6 NEPA + DEX 76.9* 88.4** 74.3* * P = ** P = 0.047

33 Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administation of moderately emetogenic chemotherapy or anthacycline and cyclophosphamide regimens in patients with cancer: a randomised, active-controlled, doubleblind, phase 3 trial Schwartzberg LS et al. Lancet Oncol 2015; 16:

34 STUDY DESIGN (1332 pts) D1 D2-3 Rolapitant 200 mg - Granisetron 2mg 2 mg Dexamethasone 20 mg Granisetron 2 mg 2 mg Dexamethasone 20 mg Rolapitant po Granisetron po Dexamethasone po Primary Endpoint: complete response on days 2-5

35 RESULTS (% complete response) RGD GD P Day % 80.3 n.s. Day % 61.6 <0.001 Day <0.001

36 CONCLUSIONS - The addition of an NK1 receptor antagonists increased the complete response in pts submitted to AC/EC on day 1 from 3% to 7% and on days 2-5 from 6% to 10% - Part of this increase is due to a dependence effect (the better results achieved on the day 1 which induced an increase of the complete responses on days 2-5)

37 Aprepitant versus dexamethasone for preventing chemotherapy-induced delayed emesis in patients with breast cancer: a randomized double-blind study Roila F, et al. J Clin Oncol 2014; 32:

38 METHODS - A randomized double-blind study comparing aprepitant versus dexamethasone was carried out in naive breast cancer patients treated with anthracyclines + cyclophosphamide - Before chemotherapy, all patients were treated with intravenous palonosetron 0.25 mg and dexamethasone 8 mg plus oral aprepitant 125 mg - On days 2 and 3 patients randomly received oral dexamethasone 4 mg bid or aprepitant 80 mg qd Primary endpoint was rate of complete response (no vomiting, no rescue treatment) from days 2-5 after chemotherapy

39 ESULTS IN THE DELAYED PHASE (551 PTS) Dexameth. Aprepit. P Value No. of patients (%) 273 (%) 278 (%) Complete response 217 (79.5) 221 (79.5) n.s. Complete protection 164 (60.1) 152 (54.7) n.s. Total control 131 (48.0) 120 (43.2) n.s. No vomiting 250 (91.6) 248 (89.2) n.s. No nausea 134 (49.1) 122 (43.9) n.s. No significant nausea 174 (63.7) 158 (56.8) n.s. Mean number of emetic episodes (sd)* 5.7 (6.5) 9.2 (9.4) n.s. Mean maximum severity of nausea (sd) 42.8 (25.9) 45.5 (24.1) n.s. Mean duration of nausea, hours (sd) 14.1 (18.4) 16.6 (21.4) n.s. * in patients who had delayed vomiting (dexamethasone: 23 patients; aprepitant: 30 patients) in patients suffering from delayed nausea (dexamethasone: 139 patients; aprepitant: 156 patients)

40 NK-1 RECEPTOR ANTAGONISTS - No comparative studies have been carried out to identify differences in efficacy and toxicity between the three NK-1 receptor antagonists. - Therefore, when available, the choice may be dependent on the respective convenience and cost.

41 OLANZAPINE Olanzapine is an antipsychotic approved drug that blocks multiple neurotransmitters in the central nervous system: dopamine D 1, D 2, D 3 receptors, serotonin 5-HT 2a, 5.HT 2c, 5-HT 3 and 5-HT 6 receptors, α 1 adrenergic receptors, muscarinic receptors and histamine H 1 receptors. Some phase II studies seems to suggest an important antiemetic activity

42 OLANZAPINE VERSUS APREPITANT FOR THE PREVENTION OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING: A RANDOMIZED PHASE III STUDY Navari RM, et al. J Support Oncol 2011; 9:

43 DESIGN OF THE STUDY (241 pts) g. 1 g. 2 g. 3 g. 4 Aprepitant po 125 mg 80 mg 80 mg - Palonosetron iv 0.25 mg Dexamethasone 12 mg 4mg bid 4mg bid 4mg bid Olanzapine po 10 mg 10 mg 10 mg 10 mg Palonosetron iv 0.25 mg Dexamethasone 20 mg dexamethasone iv on day 1 and orally on day 2-4

44 RESULTS (% COMPLETE RESPONSES) OPD APD p Day n.s. Day n.s. Day n.s.

45 It is an open study SHORTCOMINGS Due to the small sample size, the study was only powered to investigate large differences such as a 15% difference in complete response on day 1-5. It was not defined if the study was designed as a superiority, non inferiority or equivalence study. An unplanned interim analysis was carried out but the significance level was not modified according to Bonferroni s inequality.

46 OLANZAPINE FOR THE PREVENTION OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING Navari RM, et al. N Engl J Med 2016; 375:

47 DESIGN OF THE STUDY (380 pts) DAY Fosaprepitant iv 150 mg HT3 RA iv day Dexamethasone po 12 mg 8 mg 8 mg 8 mg Olanzapine po 10 mg 10 mg 10 mg 10 mg Fosaprepitant iv 150 mg HT3 RA iv day Dexamethasone po 12 mg 8 mg 8mg 8 mg

48 RESULTS (% NO NAUSEA) OFPD FPD p Day <0.001 Day Day

49 RESULTS (% COMPLETE RESPONSES) OFPD FPD p Day <0.001 Day Day <0.001

50 A DOUBLE-BLIND RANDOMIZED PHASE II STUDY OF 10 MG VERSUS 5 MG OLANZAPINE FOR EMESIS INDUCED BY HIGHLY EMETOGENIC CHEMOTHERAPY WITH CISPLATIN Hashimoto H, et al. J Clin Oncol 2016; 34 (suppl; abstr 10111)

51 DISEGNO DELLO STUDIO (153 pts) GIORNO Olanzapina os 5 mg 5 mg 5 mg 5 mg Aprepitant os 125 mg Palonosetron ev 0.75 mg Desametasone os 9.9 mg 6.6 mg 6.6 mg 6.6 mg Olanzapina os 10 mg 10 mg 10 mg 10 mg Aprepitant os 125 mg Palonosetron ev 0.75 mg Desametasone os 9.9 mg 6.6 mg 6.6 mg 6.6 mg

52 RESULTS (% COMPLETE RESPONSES) OFPD 10mg OFPD 5mg p Day n.s Day n.s. Day n.s Sedation n.s

53 ANTIEMETICS FOR THE PREVENTION OF ACUTE AND DELAYED EMESIS INDUCED BY MODERATELY EMETOGENIC CHEMOTHERAPY

54 EMETOGENIC POTENTIAL OF SINGLE INTRAVENOUS CHEMOTHERAPY AGENTS EMETIC RISK AGENT Oxaliplatin MODERATE Cytarabine > 1 gr/m 2 Carboplatin Ifosfamide Cyclophosphamide < 1500 mg/m 2 Doxorubicin Daunorubicin Epirubicin Idarubicin Irinotecan Bendamustine Alentuzumab Azacitidine

55 MODERATELY EMETOGENIC CHEMOTHERAPY The category of MEC includes antineoplastic agents with a very large risk of emesis (30% to 90%) if no antiemetics are used. This broad range makes it difficult to give one recommendation for antiemetic treatment that is appropriate for all the drugs of this category.

56 2016 MASCC/ESMO RECOMMENDATIONS For the prevention of acute emesis induced by MEC we have to use a 5-HT3 antagonist plus dexamethasone In pts receiving MEC with known potential for delayed emesis (e.g., oxaliplatin, doxorubicin, cyclophosphamide), the use of dexamethasone for days 2-3 can be considered. No routine prophylaxis can be recommended for all other pts receiving MEC.

57 NK1 ANTAGONISTS FOR THE PROPHYLAXIS OF CARBOPLATIN-INDUCED ACUTE AND DELAYED EMESIS

58 NK1 ANTAGONISTS FOR CARBOPLATIN-BASED CT Six studies evaluated the role of the addition of a NK1 antagonist to a 5-HT3 antagonist plus dexamethasone in carboplatin-treated pts. Three of the six studies presented a subgroup analysis or post hoc analysis of studies involving both AC and non-ac-treated pts. In these studies the addition of an NK1 antagonist increased the complete response by approximately 10-15%.

59 NK1 ANTAGONISTS FOR CARBOPLATIN-BASED CT In a phase III, double-blind study, 297 naїve patients with ovarian, endometrial and cervical cancer scheduled to receive carboplatin plus paclitaxel, were randomized patients to aprepitant or placebo, both combined to a 5-HT3 antagonist plus dexamethasone (Yahata H, Int J Clin Oncol 2016; 21: ) The primary endpoint was complete response, no vomiting and no significant nausea on days 2-5.

60 NK1 ANTAGONISTS FOR CARBOPLATIN-BASED CT All the primary endpoints were significantly superior with the addition of aprepitant (complete response 61.6% versus 47.3%, no vomiting 78.2% versus 54.8% and no significant nausea 85.4% versus 74.7%).

61 2016 MASCC/ESMO RECOMMENDATIONS For the prevention of carboplatin-induced acute nausea and vomiting a combination of a NK1 antagonist, dexamethasone and a 5-HT3 antagonist is recommended If patients received fosaprepitant, netupitant or rolapitant on day 1, no antiemetic prophylaxis for delayed emesis is required. If pts received aprepitant on day 1, aprepitant on days 2 and 3 is recommeded

62 MASCC/ESMO 2016 RECOMMENDATIONS ACUTE DELAYED Carboplatin 5HT3+DEX+NK1-5HT3+DEX+APR APR Oxaliplatin 5HT3+DEX DEX* Other MEC 5HT3+DEX DEX* * In pts receiving MEC with known potential for delayed emesis

63 EMETOGENIC POTENTIAL OF SINGLE INTRAVENOUS CHEMOTHERAPY AGENTS GRADO FARMACO LOW Docetaxel Aflibercept Paclitaxel Belinostat Mitoxantrone Blinatumomab Topotecan Brentuzimab Etoposide Cabazitaxel Pemetrexed Carfilzomib Methotrexate Eribulin Mitomycin Ipilimumab Gemcitabine Pertuzumab Cytarabine 100 mg/m 2 Trastuzumab-emtansine 5-Fluorouracil Vinflunine Bortezomib Nab-paclitaxel Ixabepilone Temsirolimus Pegylated liposomal doxorubicin

64 MASCC/ESMO 2016 RECOMMENDATIONS ACUTE DELAYED Low emetogenic DEX or 5HT3 - chemotherapy or a dopamine RA

65 EMETOGENIC POTENTIAL OF SINGLE INTRAVENOUS CHEMOTHERAPY AGENTS GRADO MINIMAL FARMACO Bleomycin Busulfan 2-Chlorodeoxyadenosine Fludarabine Vinblastine Vincristine Vinorelbine Nivolumab Ofatumumab Pembrolizumab Pixantrone Pralatrexate Bevacizumab

66 MASCC/ESMO 2016 RECOMMENDATIONS ACUTE DELAYED Minimal emetogenic no antiemetics no antiemetics chemotherapy

67 RECOMMENDED DOSES OF 5-HT3 RA Agent Route Antiemetics Ondansetron IV 8 mg or 0.15 mg/kg oral 16 mg Granisetron IV 1 mg or 0.01 mg/kg oral 2 mg (or 1mg) Dolasetron oral 100 mg Tropisetron IV 5 mg oral 5 mg Palonosetron IV 0.25 mg oral 0.5 mg

68 RECOMMENDED DOSES OF DEXAMETHASONE dexamethasone High risk acute emesis delayed emesis Moderate risk acute emesis delayed emesis Low risk acute emesis dose and schedule 20 mg once [12 mg when used fos(aprepitant) or netupitant] 8 mg bid for 3-4 days [8 mg once daily when used with (fo)aprepitant or netupitant] 8 mg once 8 mg daily (or 4 mg bid) for 2-3 days 4 8 mg once

69 RECOMMENDED DOSES OF NK1 RA NK1 receptor antagonist dose and schedule Aprepitant and fosaprepitant acute emesis APR 125 mg once on the day of CT or or FOS 150 mg iv once on the day of CT Rolapitant Netupitant delayed emesis 80 mg orally once daily for the 2 days after CT; or none if FOS is used 180 mg orally once on the day of CT 300 mg netupitant/0.5 mg palonosetron orally once on the day of CT

70 PREVENTION OF NAUSEA AND VOMITING INDUCED BY MULTIPLE-DAY CISPLATIN CHEMOTHERAPY

71 Randomized Phase III Double-Blind Placebo-Controlled Crossover Study Evaluating the Oral Neurokinin-1 Antagonist Aprepitant in Combination with a 5HT3 Receptor Antagonist and Dexamethasone in Patients with Germ Cell Tumors Receiving 5 day Cisplatin Combination Chemotherapy Regimens: a Hoosier Oncology Group (HOG) Study Albany C, et al, J Clin Oncol 2012; 30:

72 DESIGN OF THE STUDY (69 PTS) day 1-2 day 3 day 4-5 day 6-7 day 8 Aprepitant 125 mg 80 mg 80 mg 5-HT3 r.a. Dex 20 mg 4mgx2 4mgx2 Placebo 5-HT3 r.a. Dex 20 mg 8mgx2 4mgx2 oral aprepitant 5-HT3 iv oral dexamethasone

73 RESULTS (% COMPLETE RESPONSE) APR PL p Day < Day < Day <0.0001

74 MASCC/ESMO 2016 RECOMMENDATIONS ACUTE DELAYED Multiple-day CDDP NK1+5HT3+DEX DEX chemotherapy

75 BREAKTHROUGH CHEMOTHERAPY-INDUCED EMESIS AND REFRACTORY EMESIS

76 MASCC/ESMO 2016 RECOMMENDATIONS Breakthrough CT-induced Emesis - olanzapine Refractory emesis - another 5-HT3 - add DA or benzodiazepines - metopimazine - NK1 antagonist

77 PREVENTION OF ANTICIPATORY NAUSEA AND VOMITING

78 MASCC/ESMO 2016 RECOMMENDATIONS Anticipatory nausea and vomiting - use the best control of acute and delayed nausea and vomiting - benzodiazepines (alprazolam, diazepam and lorazepam) - behavioural therapies (progressive muscle relaxation training, hypnosis and systematic desensitisation

79 PREVENTION OF NAUSEA AND VOMITING INDUCED BY HIGH-DOSE CHEMOTHERAPY

80 MASCC/ESMO 2016 RECOMMENDATIONS ACUTE DELAYED High dose CT APR+5HT3+DEX APR

81 PREVENTION OF RADIOTHERAPY-INDUCED NAUSEA AND VOMITING

82 MASCC/ESMO 2016 RECOMMENDATIONS: Emetic Risk Area of treatment antiemetics high TBI P 5HT3+DEX moderate upper abdomen P 5HT3 ± DEX craniospinal low cranium, P or R DEX head and neck, thorax, pelvis P or R DEX, DA or 5HT3 minimal extremities, breast R DEX, DA or 5HT3 P= prophylaxis R= rescue

83 MASCC/ESMO 2016 RECOMMENDATIONS: Emetic Risk = concomitant chemo-radiotherapy antiemetic prophylaxis should be according to the guidelines for chemotherapy-induced nausea and vomiting. However, in case the emetic risk of RT is higher than that of the concomitant CT, then the risk level of RT has to be chosen to tailor the antiemetic regimen

84 EFFICACY AND SAFETY OF FOSAPREPITANT FOR THE PREVENTION OF NAUSEA AND EMESIS DURING 5 WEEKS OF CHEMORADIOTHERAPY FOR CERVICAL CANCER (THE GAND-EMESIS STUDY): A MULTINATIONAL, RANDOMISED, PLACEBO- CONTROLLED, DOUBLE-BLIND, PHASE 3 TRIAL Ruhlmann CH, et al. Lancet Oncol 2016;

85 STUDY DESIGN - Fosaprepitant vs placebo in 246 cervical cancer pts submitted to fractionated radiotherapy and weekly CDDP (40 mg/m 2 ) for 5 weeks. All pts received palonosetron 0.25 mg iv and oral DEX 16 mg before CDDP and oral DEX 8 mg bid on day 2, 4mg bid on day 3 and 4 mg on day 4. The antiemetic treatment was repeated for 5 weeks - Primary endpoint: proportion of pts with sustained no emesis after 5 weeks

86 RESULTS - The proportion of pts with sustained no emesis after 5 weeks was significantly superior with fosaprepitant (65.7% vs 48.7%). - Fosaprepitant was superior even in the day 1- day 35 rates of complete response, no emesis, no nausea and no rescue medication. - Antiemetic treatments were generally well tolerated