VOLUME 34 NUMBER 4 FEBRUARY
JOURNAL OF CLINICAL ONCOLOGY
Paul J. Hesketh, Lahey Hospital and
Medical Center, Burlington, MA; Kari
Bohlke and Mark R. Somereld, American
Society of Clinical Oncology, Alexandria;
Michael A. Danso, Virginia Oncology
Associates, Norfolk and Virginia Beach,
VA; Gary H. Lyman, Fred Hutchinson
Cancer Research Center and University of
Washington, Seattle, WA; Ethan Basch,
University of North Carolina at Chapel Hill,
Chapel Hill, NC; Maurice Chesney, patient
representative, Saunderstown, RI;
Rebecca Anne Clark-Snow, University of
Kansas Cancer Center, Westwood, KS;
Karin Jordan, University Hospital, Martin-
Luther-University Halle-Wittenberg, Halle,
Germany; and Mark G. Kris, Memorial
Sloan Kettering Cancer Center, New York,
NY.
Published online ahead of print at
www.jco.org on November 2, 2015.
ASCO Clinical Practice Guidelines
Committee approval: May 12, 2015.
Editors note: This ASCO clinical practice
guideline provides recommendations,
with comprehensive review and analyses
of the relevant literature for each
recommendation. Additional information,
including a Methodology Supplement,
slide sets, clinical tools and resources, and
links to patient information at www.
cancer.net, is available at www.asco.org/
guidelines/antiemetics and www.asco.
org/guidelineswiki.
P.J.H. and M.G.K. were update
committee co-chairs.
Authors disclosures of potential conicts
of interest are found in the article online at
www.jco.org. Author contributions are
found at the end of this article.
Corresponding author: American Society
of Clinical Oncology, 2318 Mill Rd, Suite
800, Alexandria, VA 22314; e-mail:
guidelines@asco.org.
2015 by American Society of Clinical
Oncology
0732-183X/16/3404w-381w/$20.00
DOI: 10.1200/JCO.2015.64.3635
Downloaded from ascopubs.org by 183.89.17.46 on May 24, 2017 from 183.089.017.046
1, 2016
A S C O S P E C I A L A R T I C L E
Antiemetics: American Society of Clinical Oncology
Focused Guideline Update
Paul J. Hesketh, Kari Bohlke, Gary H. Lyman, Ethan Basch, Maurice Chesney, Rebecca Anne Clark-Snow,
Michael A. Danso, Karin Jordan, Mark R. Somereld, and Mark G. Kris
A B S T R A C T
Purpose
To update a key recommendation of the American Society of Clinical Oncology antiemetic
guideline. This update addresses the use of the oral combination of netupitant (a neurokinin 1
[NK1] receptor antagonist) and palonosetron (a 5-hydroxytryptamine-3 [5-HT3] receptor antagonist)
for the prevention of acute and delayed nausea and vomiting in patients receiving chemotherapy.
Methods
An update committee conducted a targeted systematic literature review and identied two phase
III clinical trials and a randomized phase II dose-ranging study.
Results
In one phase III trial, the oral combination of netupitant and palonosetron was associated with
higher complete response rates (no emesis and no rescue medications) compared with palono-
setron alone in patients treated with anthracycline plus cyclophosphamide chemotherapy (74% v
67% overall; P 5 .001). In another phase III trial, the oral combination of netupitant and palonosetron
was safe and effective across multiple cycles of moderately or highly emetogenic chemotherapies. In
the phase II dose-ranging study, each dose of netupitant (coadministered with palonosetron 0.50 mg)
produced higher complete response rates than palonosetron alone among patients receiving cisplatin-
based chemotherapy. The highest dose of netupitant (ie, 300 mg) was most effective.
Recommendations
All patients who receive highly emetogenic chemotherapy regimens (including anthracycline
plus cyclophosphamide) should be offered a three-drug combination of an NK1 receptor antagonist, a 5-HT3
receptor antagonist, and dexamethasone. The oral combination of netupitant and palonosetron plus
dexamethasone is an additional treatment option in this setting. The remaining recommendations from the
2011 ASCO guideline are unchanged pending a full update. Additional information is available at www.
asco.org/guidelines/antiemetics and www.asco.org/guidelineswiki.
J Clin Oncol 34:381-386. 2015 by American Society of Clinical Oncology
The rst American Society of Clinical
INTRODUCTION
Oncology (ASCO) guideline for the use of antie-
metics was published in 1999,1 with updates in
The goal of this update is to provide oncologists, 20062 and 2011.3 Pending a full update of the 2011
other health care practitioners, patients, and care- guideline, this update provides expedited guidance
givers with recommendations regarding the use of regarding a new agent to prevent chemotherapy-
netupitant and palonosetron (NEPA). NEPA was induced nausea and vomiting. Recommendations
approved by the US Food and Drug Administration regarding other agents will be addressed in a
(FDA) in October 2014 for use in the prevention of subsequent, comprehensive guideline update.
acute and delayed nausea and vomiting associated
with initial and repeat courses of chemotherapy.
NEPA is administered orally and consists of a xed GUIDELINE UPDATE QUESTION
dose of 300 mg of the neurokinin-1 (NK1) receptor
antagonist netupitant combined with 0.50 mg of the Should NEPA be incorporated into existing recom-
5-hydroxytryptamine type 3 (5-HT3) receptor mendations for the prevention of chemotherapy-
antagonist palonosetron. induced nausea and vomiting?
2015 by American Society of Clinical Oncology 381
Copyright 2017 American Society of Clinical Oncology. All rights reserved.
 Hesketh et al

METHODS
Guideline Update Process
ASCO uses a signals4 approach to facilitate guideline updating. This
approach is intended to identify new, potentially practice-changing data (ie,
signals) that might translate into revised practice recommendations. The ap-
proach relies on routine literature searching and the expertise of ASCO
guideline panel members to identify signals. The Methodology Supplement
(available at www.asco.org/guidelines/antiemetics) provides additional infor-
mation about the signals approach.
For this update, the publication of phase III clinical trials fol-
lowed by FDA approval of a new antiemetic provided the signal. The
decision to address the new drug as part of an update was made by the
update committee co-chairs (P.J.H., M.G.K.) and two steering com-
mittee members (G.H.L., E.B.). The full ASCO Update Committee
(Appendix Table A1, online only) was then convened to review the
evidence.
Evidence was collected through a systematic review of the medical liter-
ature. Publications were included if they were phase II or III randomized
clinical trials of NEPA among patients with a malignant neoplasm. These
publications were identied by searching PubMed, with no date restrictions,

THE BOTTOM LINE

Antiemetics: American Society of Clinical Oncology Focused Guideline Update

Intervention
Antiemetics for patients receiving cancer therapy.

Target Audience
Medical oncologists, radiation oncologists, oncology nurses, patients, caregivers.

Key Recommendations
Updated recommendation: All patients who receive highly emetogenic chemotherapy regimens (including anthracycline plus
cyclophosphamide) should be offered a three-drug combination of a neurokinin 1 receptor antagonist, a 5-
hydroxytryptamine-3 (5-HT3) receptor antagonist, and dexamethasone. The oral combination of netupitant and
palonosetron (NEPA) plus dexamethasone is an additional treatment option in this setting.
The preferred 5-HT3 receptor antagonist for patients who receive moderately emetogenic chemotherapy regimens is
palonosetron; antiemetic treatment includes that agent combined with a corticosteroid.

Antiemetic treatment for patients who receive combination chemotherapy should be determined according to the agent with
the greatest degree of emetic risk.
Both dexamethasone and a 5-HT3 receptor antagonist are recommended for patients receiving high-dose chemotherapy.
Pediatric patients receiving either highly or moderately emetogenic chemotherapy should be treated with a 5-HT3 receptor
antagonist and corticosteroids; higher weight-based dosing may be required.

For those treated with highly emetogenic radiation therapy, a 5-HT3 receptor antagonist before each fraction and a 5-day
course of dexamethasone are recommended.
A 5-HT3 receptor antagonist before each fraction is also recommended before moderately emetogenic radiation therapy; a 5-
day course of dexamethasone is optional.
For patients who receive combination chemotherapy and radiotherapy, antiemetic therapy is dictated by the emetogenicity of
chemotherapy, unless the emetic risk of radiation therapy is higher.

Methods
An update committee reviewed the results of two phase III randomized trials and one randomized dose-ranging study of NEPA.

Additional Resources
Additional information is available at www.asco.org/guidelines/antiemetics and www.asco.org/guidelineswiki. Patient information is
available at www.cancer.net.
ASCO believes that cancer clinical trials are vital to inform medical decisions and improve cancer care and that all patients should have
the opportunity to participate.

382 2015 by American Society of Clinical Oncology JOURNAL OF CLINICAL ONCOLOGY

Downloaded from ascopubs.org by 183.89.17.46 on May 24, 2017 from 183.089.017.046

Copyright 2017 American Society of Clinical Oncology. All rights reserved.
 Antiemetics: Focused Update of ASCO Guideline

for the term netupitant. Of the 32 publications identied, three met the
eligibility criteria and form the evidence base for this update.
The update committee contributed to the development of the guideline,
provided critical review, and nalized the guideline recommendation. All
ASCO guidelines are reviewed and approved by the ASCO Clinical Practice
Guidelines Committee.
Guideline Disclaimer
The clinical practice guideline update and other guidance published
herein are provided by ASCO to assist providers in clinical decision making.
The information herein should not be relied on as being complete or accurate,
nor should it be considered as inclusive of all proper treatments or methods of
care or as a statement of the standard of care. With the rapid development of
scientic knowledge, new evidence may emerge between the time information
is developed and when it is published or read. The information is not con-
tinually updated and may not reect the most recent evidence. The information
addresses only the topics specically identied herein and is not applicable to
other interventions, diseases, or stages of diseases. This information does not
mandate any particular course of medical care. Furthermore, the information
is not intended to substitute for the independent professional judgment of the
treating provider, because the information does not account for individual
variation among patients. Recommendations reect high, moderate, or low
condence that the recommendation reects the net effect of a given course of
action. The use of words like must, must not, should, and should not
indicates that a course of action is recommended or not recommended for
either most or many patients, but there is latitude for the treating physician to
select other courses of action in individual cases. In all cases, the selected course
of action should be considered by the treating provider in the context of
treating the individual patient. Use of the information is voluntary. ASCO
provides this information on an as-is basis and makes no warranty, express
or implied, regarding the information. ASCO specically disclaims any
warranties of merchantability or tness for a particular use or purpose.
ASCO assumes no responsibility for any injury or damage to persons or
property arising out of or related to any use of this information or for any
errors or omissions.
This is the most recent information as of the publication date. For
the most recent information or to submit new evidence, please visit
www.asco.org/guidelines/antiemetics and the ASCO Guidelines Wiki
(www.asco.org/guidelineswiki).
Guideline and Conflicts of Interest
The update committee was assembled in accordance with the ASCO
Conicts of Interest Management Procedures for Clinical Practice Guidelines
(summarized at www.asco.org/rwc). Members of the commitee completed
the ASCO disclosure form, which requires disclosure of nancial and other
interests that are relevant to the subject matter of the guideline, including

Table 1. Design and Results of Randomized Studies of NEPA

Any Treatment-
Complete Response (no Related
Study Intervention/ No. of emesis or rescue Adverse Event
Author (year) Design Study Population Comparison Patients medication; %) (%) Conclusion
Hesketh et al7 Randomized Chemotherapy-naive patients PALOa 136 76.5 (reference) 12.5 Each NEPA dose provided
(2014) phase II undergoing cisplatin-based NEPA100b 135 87.4 (P 5 .018) 13.3 superior prevention of
chemotherapy for solid NEPA200c 137 87.6 (P 5 .017) 17.4 nausea and vomiting
tumors NEPA300d 135 89.6 (P 5 .004) 15.4 compared with PALO;
NEPA300 had highest
APR 1 ONDe 134 86.6 (P # .05) 19.4
efcacy
Aapro et al5 Phase III Chemotherapy-naive patients PALOf 725 Acute, 85.0 7.2 NEPA was superior to
(2014) receiving anthracycline Delayed, 69.5 PALO in preventing
plus cyclophosphamide Overall, 66.6 chemotherapy-induced
chemotherapy for solid NEPAg 724 Acute, 88.4 (P 5 .047) 8.1 nausea and vomiting
tumors
Delayed, 76.9 (P 5 .001)
Overall, 74.3 (P 5 .001)
Gralla et al6 Phase IIIh Chemotherapy-naive patients APR 1 104 Cycle one, 76 Cycle one, 2.9 NEPA was safe and
(2014) scheduled to receive PALOi 96 Cycle two, 81 Cycle two, 1.0 effective over repeated
repeated courses of 91 Cycle three, 87 Cycle three, 2.2 cycles of highly and
highly or moderately 81 Cycle four, 88 Cycle four, 1.2 moderately emetogenic
emetogenic chemotherapy
57 Cycle ve, 86 Cycle ve, 1.8
chemotherapy
43 Cycle six, 86 Cycle six, 0.0
NEPAj 308 Cycle one, 81 Cycle one, 5.2
279 Cycle two, 86 Cycle two, 4.3
258 Cycle three, 91 Cycle three, 1.9
232 Cycle four, 90 Cycle four, 1.3
156 Cycle ve, 92 Cycle ve, 0.6
124 Cycle six, 91 Cycle six, 1.6

Abbreviations: APR, aprepitant; NEPA, netupitant plus palonosetron; OND, ondansetron; PALO, palonosetron.
a
PALO: day 1, oral PALO 0.50 mg plus oral dexamethasone 20 mg plus placebo; days 2 to 4, oral dexamethasone 8 mg twice per day.
b
NEPA100: day 1, oral netupitant 100 mg plus oral PALO 0.50 mg plus oral dexamethasone 12 mg; days 2 to 4, oral dexamethasone 4 mg twice per day.
c
NEPA200: day 1, oral netupitant 200 mg plus oral PALO 0.50 mg plus oral dexamethasone 12 mg; days 2 to 4, oral dexamethasone 4 mg twice per day.
d
NEPA300: day 1, oral netupitant 300 mg plus oral PALO 0.50 mg plus oral dexamethasone 12 mg; days 2 to 4, oral dexamethasone 4 mg twice per day.
e
APR 1 OND: day 1, oral APR 125 mg plus intravenous OND 32 mg plus oral dexamethasone 12 mg; days 2 to 3, oral APR 80 mg in morning plus oral dexamethasone
4 mg twice per day; day 4, oral dexamethasone 4 mg twice per day.
f
PALO: day 1, oral PALO 0.50 mg plus oral dexamethasone 20 mg.
g
NEPA: day 1, oral netupitant 300 mg plus oral PALO 0.50 mg plus oral dexamethasone 12 mg.
h
No formal statistical comparisons were performed; data are descriptive only.
i
APR 1 PALO: oral APR 125 mg on day 1 and 80 mg on days 2 to 3 plus oral PALO 0.50 mg day 1 plus dexamethasone. For highly emetogenic chemotherapy,
dexamethasone dosing was 12 mg on day 1 and 8 mg on days 2 to 4. For moderately emetogenic chemotherapy, dexamethasone dosing was 12 mg on day 1.
j
NEPA: NEPA 300 mg plus PALO 0.50 mg plus dexamethasone. For highly emetogenic chemotherapy, dexamethasone dosing was 12 mg on day 1 and 8 mg on days 2
to 4. For moderately emetogenic chemotherapy, dexamethasone dosing was 12 mg on day 1.

www.jco.org 2015 by American Society of Clinical Oncology 383

Downloaded from ascopubs.org by 183.89.17.46 on May 24, 2017 from 183.089.017.046

Copyright 2017 American Society of Clinical Oncology. All rights reserved.
 Hesketh et al

relationships with commercial entities that are reasonably likely to experience
direct regulatory or commercial impact as a result of promulgation of the
guideline. Categories for disclosure include employment; leadership; stock or
other ownership; honoraria, consulting or advisory role; speakers bureau;
research funding; patents, royalties, other intellectual property; expert testi-
mony; travel, accommodations, or expenses; and other relationships. In accor-
dance with these procedures, the majority of the members of the commitee did
not disclose any such relationships.
RESULTS
Two phase III randomized trials and one phase II randomized trial
form the evidence base for this update5-7 (Tables 1 and 2). A phase III
trial compared NEPA with palonosetron among 1,449 patients receiv-
ing anthracycline plus cyclophosphamide chemotherapy for solid
tumors.5 Patients in both arms received dexamethasone on day 1 only.
Use of palonosetron and dexamethasone (rather than three-drug reg-
imen) by the control group was specied by regulatory agencies.
Compared with palonosetron, NEPA resulted in higher rates of
complete response (no emesis or rescue medication) during both the
acute and delayed phases. The secondary end points of no emesis, no
signicant nausea, and complete protection (complete response and
no signicant nausea) were also better in the NEPA arm. The safety
prole of NEPA was generally similar to that of palonosetron.
Ninety-four of 725 patients in the NEPA arm reported a severe
adverse event, but only ve (0.7%) had a severe treatment-related
adverse event. The most common treatment-related adverse events
were headache (NEPA arm, 3.3%; palonosetron arm, 3.0%) and
constipation (both arms, 2.1%).
The safety and efcacy of NEPA over repeated cycles of chemo-
therapy were evaluated in a second phase III trial.6 The study enrolled
chemotherapy-naive patients treated with highly or moderately eme-
togenic chemotherapy. Patients with breast cancer treated with an-
thracycline plus cyclophosphamide chemotherapy were not eligible.
Study participants were randomly assigned to treatment with NEPA
or oral aprepitant plus oral palonosetron. Participants in both study
arms received dexamethasone on a schedule based on chemotherapy
emetogenicity. Only descriptive statistics were provided, with no for-
mal testing of between-group differences. Ninety-eight percent of
patients completed cycle one, 75% completed at least four cycles, and
40% completed six cycles. The rate of complete response with NEPA
remained high across cycles. Treatment-emergent adverse events
occurred in 86% of patients in the NEPA arm and 91.3% of patients in
the aprepitant plus palonosetron arm; a majority of these events were
mild or moderate. Adverse effects that were considered to be related to
the study drug occurred in 10.1% of patients in the NEPA arm and
5.8% of patients in the aprepitant plus palonosetron arm. The most
common treatment-related adverse events in the NEPA arm were
constipation (3.6%) and headache (1.0%). Only one adverse event
was classied as severe and possibly related to antiemetic treatment: A
patient in the NEPA arm experienced acute psychosis in cycle one and
discontinued treatment. This event was also thought to be possibly
related to dexamethasone. Adverse events did not increase across
study cycles.
The randomized phase II dose-ranging trial enrolled 694
chemotherapy-naive patients with solid tumors who were scheduled
to receive cisplatin-based chemotherapy.7 Patients were randomly
assigned to one of ve different antiemetic treatment arms: netupitant
at 100, 200, or 300 mg, each combined with oral palonosetron 0.50 mg;
oral palonosetron 0.50 mg alone; or an exploratory arm of standard
3-day aprepitant plus intravenous ondansetron 32 mg. All patients
received oral dexamethasone on days 1 through 4. The primary analysis
compared each dose of NEPA with palonosetron; the study was

Table 2. Type of Chemotherapy by Study Arm in Randomized Studies of NEPA

Study Arm (%)*
Chemotherapy Agent NEPA100 NEPA200 NEPA300 PALO APR 1 OND APR 1 PALO
Hesketh et al7 (2014)
Cisplatin alone 15.6 14.6 14.1 15.4 14.9
Concomitant low 45.9 56.9 48.1 52.9 52.2
Concomitant moderate or high 38.5 28.5 37.8 31.6 32.8
Aapro et al5 (2014)
Cyclophosphamide 99.9 100
Doxorubicin 68.0 63.7
Epirubicin 32.0 36.3
Gralla et al6 (2014)
Moderately emetogenic chemotherapy 75.7 75.7
Carboplatin 60.3 61.5
Oxaliplatin 20.1 24.4
Doxorubicin 11.1 6.4
Cyclophosphamide 3.4 2.6
Irinotecan 3.0 3.8
Epirubicin 1.7 1.3
Daunorubicin 0.4 0
Highly emetogenic chemotherapy 24.3 24.3
Cisplatin 96.0 92.0
Dacarbazine 4.0 4.0
Carmustine 0 4.0

Abbreviations: APR, aprepitant; NEPA, netupitant plus palonosetron; OND, ondansetron; PALO, palonosetron.
*Table 1 footnotes provide description of antiemetic regimen used in each arm of each study.

384 2015 by American Society of Clinical Oncology JOURNAL OF CLINICAL ONCOLOGY

Downloaded from ascopubs.org by 183.89.17.46 on May 24, 2017 from 183.089.017.046

Copyright 2017 American Society of Clinical Oncology. All rights reserved.
 Antiemetics: Focused Update of ASCO Guideline

Table 3. Antiemetic Dosing by Chemotherapy Risk Category

Emetic Risk Category Dose on Day of Chemotherapy Dose on Subsequent Days
High*
NK1 receptor antagonist
Aprepitant 125 mg orally 80 mg orally on days 2 and 3
Fosaprepitant 150 mg IV
5-HT3 receptor antagonist
Granisetron 2 mg orally or 1 mg or 0.01 mg/kg IV
Ondansetron 8 mg orally twice daily or 8 mg or 0.15 mg/kg IV
Palonosetron 0.50 mg orally or 0.25 mg IV
Dolasetron 100 mg orally only
Tropisetron 5 mg orally or 5 mg IV
Ramosetron 0.3 mg IV
Combined NK1 receptor antagonist
and 5-HT3 receptor antagonist
NEPA 300 mg netupitant and 0.50 mg palonosetron
orally
Corticosteroid if aprepitant is used
Dexamethasone 12 mg orally or IV 8 mg orally or IV on days 2 to 3 or days 2 to 4
Corticosteroid if fosaprepitant is used
Dexamethasone 12 mg orally or IV 8 mg orally or IV on day 2; 8 mg orally or IV
twice daily on days 3 to 4
Corticosteroid if NEPA is used
Dexamethasone 12 mg orally or IV 8 mg orally or IV once daily on days 2 to 4
Moderate
5-HT3 receptor antagonist
Palonosetron 0.25 mg IV or 0.50 mg orally
Corticosteroid
Dexamethasone 8 mg orally or IV 8 mg on days 2 and 3 orally or IV
Low
Corticosteroid
Dexamethasone 8 mg orally or IV

NOTE. For patients receiving multiday chemotherapy, clinicians must rst determine emetic risk of agents included in regimen. Patients should receive agent of highest
therapeutic index daily during chemotherapy and for 2 days thereafter. Patients can also be offered granisetron transdermal patch, which delivers therapy over multiple
days, rather than receiving antagonist daily.
Abbreviations: 5-HT3, 5-hydroxytryptamine-3; IV, intravenously; NEPA, netupitant plus palonosetron; NK1, neurokinin 1.
*Includes combination of anthracycline and cyclophosphamide.
Dexamethasone dose is for patients who are receiving recommended three-drug regimen for highly emetic chemotherapy. If patients do not receive NK1 receptor
antagonist, dexamethasone dose should be adjusted to 20 mg on day 1 and 16 mg on days 2 to 4.
Clinicians who choose to use NK1 receptor antagonist should follow highly emetic chemotherapy dosing. Importantly, corticosteroid is administered only on day 1;
dexamethasone dose is 12 mg.

not powered to detect a difference between NEPA and aprepitant

plus ondansetron. Compared with palonosetron alone, each dose
of NEPA produced higher overall complete response rates (no
emesis or rescue). Complete response rates with the highest dose
of NEPA were statistically signicantly higher than those of
palonosetron alone during both the acute and delayed phases.
The highest dose of NEPA was also signicantly associated (P ,
.05) with improvements in the secondary outcomes of no emesis,
no signicant nausea, and complete protection. The frequency
and intensity of adverse events were generally similar across study
arms, and a majority of adverse events were mild or moderate.
The most common treatment-related adverse events were hiccups
and headache. One serious event in a NEPA-treated patient
(NEPA200) was felt to be treatment related: The patient experi-
enced loss of consciousness, recovered 30 minutes after onset,
and discontinued treatment. On the basis of these results, the
highest dose of NEPA (300 mg) was selected for further
development.
The chemotherapy agents used in each arm of each study are
listed in Table 2. The safety and efcacy of NEPA in weekly or
every-2-week chemotherapy regimens have not been evaluated.
DISCUSSION
In both a phase III trial in patients receiving the combination of an
anthracycline and cyclophosphamide and a large phase II dose-
ranging trial in patients receiving cisplatin, NEPA (combined NK1/
5-HT3 receptor antagonist) combined with dexamethasone was
superior to palonosetron combined with dexamethasone in the
prevention of chemotherapy-induced nausea and vomiting. In a
second phase III trial in patients receiving highly or moderately
emetogenic chemotherapy over multiple cycles of treatment, NEPA
was also effective in preventing nausea and vomiting. NEPA was
well tolerated in all three studies, with a safety prole similar to that
of the control arms. Dosing information for NEPA and other
antiemetics is summarized in Table 3.
UPDATED RECOMMENDATION
All patients who receive highly emetogenic chemotherapy regimens
(including anthracycline plus cyclophosphamide) should be offered a

www.jco.org 2015 by American Society of Clinical Oncology 385

Downloaded from ascopubs.org by 183.89.17.46 on May 24, 2017 from 183.089.017.046

Copyright 2017 American Society of Clinical Oncology. All rights reserved.
 Hesketh et al

three-drug combination of an NK1 receptor antagonist, a 5-HT3 particular interest are emerging data on the psychotropic medication
receptor antagonist, and dexamethasone. The oral combination of olanzapine. Olanzapine is inexpensive, but high-quality evidence of
NEPA plus dexamethasone is an additional treatment option in this efcacy and safety has been lacking. Additional evidence from two
setting. The remaining recommendations from the 2011 ASCO guideline completed phase III studies is eagerly anticipated.
are unchanged pending a full update. The full set of recom-
mendations is listed in the Bottom Line Box.
AUTHORS DISCLOSURES OF POTENTIAL CONFLICTS
OF INTEREST
COST CONSIDERATIONS
Disclosures provided by the authors are available with this article at
www.jco.org.
Formal cost-effectiveness analyses of NEPA are not yet available. Be-
cause NEPA is an all-oral regimen, it will require patients to both ll
and pay for a prescription. The out-of-pocket cost will vary by insur- AUTHOR CONTRIBUTIONS
ance plan, and this point should be discussed with patients. The value
of NEPA will be inuenced by the cost and effectiveness of other Administrative support: Kari Bohlke
antiemetic options, and these will be explored more fully in the Manuscript writing: All authors
planned, comprehensive update of the ASCO antiemetic guideline. Of Final approval of manuscript: All authors

REFERENCES
1. Gralla RJ, Osoba D, Kris MG, et al: Recom-
mendations for the use of antiemetics: Evidence-
based, clinical practice guidelinesAmerican Society
of Clinical Oncology. J Clin Oncol 17:2971-2994, 1999
2. Kris MG, Hesketh PJ, Somereld MR, et al:
American Society of Clinical Oncology guideline for
antiemetics in oncology: Update 2006. J Clin Oncol
24:2932-2947, 2006
3. Basch E, Prestrud AA, Hesketh PJ, et al:
Antiemetics: American Society of Clinical Oncology
clinical practice guideline update. J Clin Oncol 29:
4189-4198, 2011
4. Shojania KG, Sampson M, Ansari MT, et al:
How quickly do systematic reviews go out of date?
A survival analysis. Ann Intern Med 147:224-233,
2007
5. Aapro M, Rugo H, Rossi G, et al: A randomized
phase III study evaluating the efcacy and safety of
NEPA, a xed-dose combination of netupitant and
palonosetron, for prevention of chemotherapy-
induced nausea and vomiting following moderately
emetogenic chemotherapy. Ann Oncol 25:1328-1333,
2014
6. Gralla RJ, Bosnjak SM, Hontsa A, et al: A phase
III study evaluating the safety and efcacy of NEPA, a
xed-dose combination of netupitant and palonose-
tron, for prevention of chemotherapy-induced nausea
and vomiting over repeated cycles of chemotherapy.
Ann Oncol 25:1333-1339, 2014
7. Hesketh PJ, Rossi G, Rizzi G, et al: Efcacy
and safety of NEPA, an oral combination of
netupitant and palonosetron, for prevention of
chemotherapy-induced nausea and vomiting fol-
lowing highly emetogenic chemotherapy: A ran-
domized dose-ranging pivotal study. Ann Oncol 25:
1340-1346, 2014

n n n

386 2015 by American Society of Clinical Oncology JOURNAL OF CLINICAL ONCOLOGY

Downloaded from ascopubs.org by 183.89.17.46 on May 24, 2017 from 183.089.017.046

Copyright 2017 American Society of Clinical Oncology. All rights reserved.
 Antiemetics: Focused Update of ASCO Guideline

AUTHORS DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Antiemetics: American Society of Clinical Oncology Focused Guideline Update
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are
self-held unless noted. I 5 Immediate Family Member, Inst 5 My Institution. Relationships may not relate to the subject matter of this manuscript. For more
information about ASCOs conict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc.
Paul J. Hesketh Consulting or Advisory Role: Merck, Tesaro
No relationship to disclose Travel, Accommodations, Expenses: Merck
Kari Bohlke Michael A. Danso
No relationship to disclose No relationship to disclose
Gary H. Lyman Karin Jordan
Research Funding: Amgen (Inst) Consulting or Advisory Role: Merck, Merck Sharp & Dohme, Helsinn
Therapeutics, Pro Strakan
Ethan Basch
No relationship to disclose Mark R. Somereld
No relationship to disclose
Maurice Chesney
Stock or Other Ownership: Teva Pharmaceutical Industries, Bristol-Myers Mark G. Kris
Squibb, Pzer, Pzer (I), Procter & Gamble, Walgreens, Walgreens (I) Consulting or Advisory Role: AstraZeneca, Clovis Oncology, ARIAD
Pharmaceuticals, Genentech/Roche, Pzer, Daiichi Sankyo, Threshold
Rebecca A. Clark-Snow Pharmaceuticals, Array BioPharma
Honoraria: Merck Research Funding: Puma Biotechnology (Inst), Pzer (Inst)

www.jco.org 2015 by American Society of Clinical Oncology

Downloaded from ascopubs.org by 183.89.17.46 on May 24, 2017 from 183.089.017.046

Copyright 2017 American Society of Clinical Oncology. All rights reserved.
 Hesketh et al

Acknowledgment

We thank Mariana Chavez MacGregor, Alex Solky, and the American Society of Clinical Oncology Clinical Practice Guidelines Committee
for their thoughtful reviews of and insightful comments on this guideline document.

Appendix

Table A1. Update Committee Membership

Member Afliation
Paul J. Hesketh, MD (co-chair) Lahey Hospital and Medical Center, Burlington, MA
Mark G. Kris, MD (co-chair) Memorial Sloan Kettering Cancer Center, New York, NY
Gary H. Lyman, MD, MPH (steering committee) Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA
Ethan Basch, MD, MSc (steering committee) University of North Carolina at Chapel Hill, Chapel Hill, NC
Maurice Chesney Patient representative, Saunderstown, RI
Rebecca Anne Clark-Snow, RN, BSN, OCN University of Kansas Cancer Center, Westwood, KS
Michael A. Danso, MD Virginia Oncology Associates, Norfolk and Virginia Beach, VA
Karin Jordan, MD University Hospital, Martin-Luther-University Halle-Wittenberg, Halle, Germany

NOTE. American Society of Clinical Oncology staff: Kari Bohlke, ScD, and Mark R. Somereld, PhD.

2015 by American Society of Clinical Oncology JOURNAL OF CLINICAL ONCOLOGY

Downloaded from ascopubs.org by 183.89.17.46 on May 24, 2017 from 183.089.017.046

Copyright 2017 American Society of Clinical Oncology. All rights reserved.