Print This Article
Educational Affairs
New Oral Oncolytics of 2017: Key Points for a Counseling Pharmacist
by Janna Afanasjeva, PharmD, BCPSa; Chloe Majkowski, PharmD Candidate 2018a; Christopher Campbell, PharmD, BCPS, BCOPb; Institutional affiliations: aUniversity of Illinois Chicago; bNorthwestern Memorial Hospital
The research in oncology has
been increasing over the past few years, and the availability of oral oncolytic
agents has also surged.1,2
Oral formulations comprise about 25% to
35% of oncology medications in the pipeline. For the year 2017, the Food and Drug
Administration (FDA) approved 8 oral oncolytics
that are new molecular entities.3
As more oral oncolytics become available on the market, more
opportunities exist for pharmacists to provide direct patient care to patients
with cancer.2,4 One of the key
services that pharmacists can provide is patient education. In fact, patient
education is extremely important for oral oncolytics
because patients take these medications
at home without direct supervision of a
treating physician. Oral oncolytics have
similar benefits and drawbacks as intravenous medications, and therefore,
patients must completely understand proper drug administration, importance of adherence, and possible adverse
events. This article reviews new oral oncolytics
that have been approved by the FDA in the year
2017. The goal of the article is to briefly introduce and describe new agents
and their efficacy and safety data so that practicing pharmacists in a variety
of settings can counsel on these agents if the need arises.
This article also mentions the
cost of agents (see Table 1). The affordability is a particular concern with
oral oncolytics as copays tend to be
higher for them compared to intravenous medications that are administered in
infusion clinics.5
Prescription drug benefits typically cover the cost of oral oncolytics while medical insurance for
physician office visits covers intravenous medications resulting in lower costs
to patients. Although some states are working on legislation to ensure
comparable coverage between oral and intravenous oncolytics, a federal law in this area is lacking. Pharmacists may
need to work with patients, oncology providers, and prescription drug benefits
to confirm that patients are able to afford and adhere to new oncolytics.
Abemaciclib (Verzenio)
Abemaciclib inhibits cyclin-dependent kinases 4 and 6 (CDK4
and CDK6). These kinases are responsible for phosphorylation of the
retinoblastoma protein (Rb), cell cycle progression, and cell proliferation.
Indication
Abemaciclib is approved for use as a monotherapy or in
combination with fulvestrant for hormone-receptor (HR)-positive and human
epidermal growth factor 2 (HER2)-negative advanced or metastatic breast cancer
after patients have progressed on endocrine therapy.6 Abemaciclib is also approved as initial
therapy in combination with an aromatase inhibitor for postmenopausal women
with HR-positive, HER-2 negative advanced or metastatic breast cancer. The
monotherapy approval requires prior chemotherapy
but is unique that it is the only drug in class to be used as stand-alone
therapy.
Efficacy
The approval of abemaciclib
was based on 3 clinical trials: MONARCH1, MONARCH2, and MONARCH3.6 MONARCH1 was an open-label phase 2
study of abemaciclib monotherapy (200 mg
every 12 hours until disease progression or unacceptable toxicity) in 132 women
with HR-positive HER2-negative metastatic breast cancer who have progressed on
endocrine therapy.7 The
objective response rate (ORR), which was the primary endpoint, was 19.7% (95%
CI, 13.3% to 27.5%). Median progression-free survival (PFS) was 6 months, and
overall survival (OS) was 17.7 months.
MONARCH2 was a double-blind, phase 3 study of abemaciclib (150 mg twice daily) with
fulvestrant versus fulvestrant alone in 669 women with HR-positive
HER2-negative advanced breast cancer, who have progressed on endocrine therapy.8 Median PFS, the primary endpoint, was
16.4 months in the combination group versus 9.3 months in the fulvestrant group
(hazard ratio, 0.55; 95% confidence interval (CI), 0.45 to 0.68; p<0.001).
The ORR was 48.1% (95% CI, 42.6% to 53.6%) in the combination group and 21.3%
(95% CI, 15.1% to 27.6%) in the fulvestrant group. At the time of the
publication, OS results were not mature.
The approval for abemaciclib in combination with an aromatase
inhibitor as initial therapy for postmenopausal women with advanced or
metastatic breast cancer was based on results from the MONARCH3 trial.9 This was a double-blind, phase 3 study
of 493 patients with no prior systemic therapy in the advanced setting.
Patients were randomized to receive abemaciclib 150 mg or placebo twice daily
in addition to physician’s choice of letrozole (80% of patients) or anastrozole
(20% of patients). Median PFS was prolonged in the abemaciclib group with a
hazard ratio of 0.54 (95% CI, 0.41 to 0.72; p = 0.000021). The median was not
reached in the abemaciclib arm, and the median PFS in the placebo group was
14.7 months. The ORR was 48.2% (95% CI, 42.8% to 53.6%) in the abemaciclib
group versus 34.5% (95% CI, 27.3% to 41.8%) in the placebo group.
Safety
In MONARCH 1, the most common grade 3 adverse events with abemaciclib were diarrhea (19.7%), fatigue
(12.9%), and nausea (4.5%).7
The only grade 4 event in MONARCH1 was decreased neutrophil count (4.6%).
Adverse events led to discontinuation of treatment in 7.6% of patients. In MONARCH2, the most common grade 3 or 4 adverse
events with abemaciclib were neutropenia
(26.5%), diarrhea (13.4%), and leukopenia (8.8%).8 The most common grade 3 or 4 adverse events in the MONARCH3
with the abemaciclib group were neutropenia (21.1%), diarrhea (9.5%), and
leukopenia (7.6%).9 Guidelines
Per National Comprehensive Cancer Network (NCCN) Breast
Cancer guidelines, abemaciclib plus an aromatase inhibitor is recommended as a
preferred regimen for HR-positive, HER2-negative recurrent or metastatic breast
cancer in postmenopausal women and may be considered as a first-line option for
patients without previous systemic therapy.10
Abemaciclib plus fulvestrant is also listed as a preferred regimen for
postmenopausal patients with advanced or metastatic HR-positive, HER2-negative
breast cancer but is only indicated after progression on prior endocrine
therapy. Abemaciclib monotherapy is listed as useful in certain circumstances
for this population.
Acalabrutinib (Calquence)
Acalabrutinib
inhibits Bruton tyrosine kinase (BTK) more selectively than first-generation
BTK inhibitors. These kinases are involved in downstream signaling pathways
vital to malignant B-cell proliferation and survival.
Indication
Acalabrutinib received accelerated approval for use as monotherapy
for mantle cell lymphoma (MCL) after patients have progressed on at least 1 prior therapy.11
Efficacy
The accelerated
approval of acalabrutinib was based on
ORR in Trial LY-004, an open-label, phase 2 study.11 Acalabrutinib was administered (100 mg twice daily until
disease progression or unacceptable toxicity) in 124 relapsed or refractory
(r/r) MCL patients, who had at least 1 prior therapy.12 The primary endpoint, ORR, was 81 %
80% (95% CI, 73% 72% to 87%). The trial reported a complete response (CR) in
40% of patients and partial response in 41% of patients, with a median time to
best response of 1.9 months. After 15.2 months of follow-up, the median
duration of response (DOR) had not been reached.
Safety
In Trial LY-004, the most common non-hematologic adverse effects
(AEs) of acalabrutinib were headache, diarrhea, fatigue, myalgia, and
bruising. Decreased hemoglobin (46%), platelets (44%), and neutrophils (36%)
were very common. The most common Grade 3 or greater toxicities were diarrhea,
neutropenia, thrombocytopenia, and anemia. Dose reductions or discontinuations
due to any AE were reported in 1.6% and
6.5% patients, respectively.12 Similar to first-generation BTK inhibitor, ibrutinib, the package
insert for acalabrutinib carries warnings
for hemorrhage, infection, cytopenias, second primary malignancies, and atrial
arrhythmias.11,13 Transient
lymphocytosis may also occur with a median time to onset of 1.1 weeks and
median duration of 6.7 weeks.
Guidelines
Per NCCN B-Cell Lymphomas guideline, acalabrutinib is recommended as a second-line single-agent therapy
for patients with stage I or II disease, aggressive stage II bulky, III, or IV
disease, or symptomatic indolent stage II bulky, III, or IV disease to achieve
a CR after partial response to induction therapy or for relapsed, refractory,
or progressive disease.14 The
NCCN chronic lymphocytic leukemia (CLL) guideline provides a category 2A
recommendation for acalabrutinib as a single agent therapy for relapsed or
refractory disease with or without del(17p)/TP53 mutation.15 Of note, acalabrutinib should not be
used for ibrutinib-refractory CLL or small lymphocytic lymphoma in patients
with BTK C481S mutations.
Brigatinib (Alunbrig)
Brigatinib is a
tyrosine kinase inhibitor with broad activity against multiple kinases
including ALK, c-ros oncogene 1 (ROS1),
insulin-like growth factor-1 receptor (IGF-1R), and fetal liver tyrosine kinase
3 (FLT-3) including epidermal growth factor receptor (EGFR) deletion and point
mutations. Brigatinib inhibits ALK and blocks a signaling cascade with downstream
effects on proteins STAT3, AKT, ERK1/2, and S6. Brigatinib’s
mechanism of action allows for activity despite ALK-inhibitor resistance due to
EML4-ALK and 17 other mutant forms, even after progression on crizotinib.
Indication
Brigatinib received accelerated approval for
use in non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma
kinase (ALK)-positive metastatic disease after crizotinib.16
Efficacy
The accelerated
approval of brigatinib was based on
clinically significant and durable ORR in the ALTA trial, an open-label,
two-arm, phase 2 study. Brigatinib was
administered (either 90 mg once daily or 180 mg once daily with an initial
7-day lead-in of 90 mg daily) in 222 patients with locally advanced or
metastatic ALK-positive NSCLC and who were previously treated with crizotinib.17 The primary endpoint, ORR, was 48 %
(95% CI, 39% to 58%) and 53% (95% CI, 43% to 62%) in the 90 mg and 180 mg arms,
respectively. Brigatinib showed clinically meaningful improvement in measurable
brain metastases in both arms. Most of the intracranial
responses were durable for at least 4 months. The trial reported a total of
3.6% or 4.5% CRs and 45% or 48% partial responses, in the 90 mg and 180 arms,
respectively. The median DOR was 13.8 months. The PFS was 12.9 months in the
180 mg group and 9.2 months in the 90 mg group.
Safety
In the published abstract of the
ALTA trial, the most common AEs in the 90 mg and 180 mg groups were nausea (33%
and 40%), diarrhea (19% and 38%), headache (28 and 27%), and cough (18% and
34%), while less than 10% of patients experienced grade 3 events including
hypertension, increased blood creatine phosphokinase (CPK), pneumonia, and
increased lipase.17 Notably,
pulmonary AEs were more common among patients (6%) in the lead-in phase. The
abstract reports no increase in serious pulmonary events after escalation to
180 mg. According to the package insert,
brigatinib commonly led to increases in
liver and pancreatic enzymes and has a warning for amylase, lipase, CPK, and
glucose elevations. Caution is advised regarding the development of
hypertension and bradycardia.16
Guidelines
The NCCN NSCLC
guideline recommends brigatinib as monotherapy for ALK-positive recurrent
or metastatic disease for patients,
who are refractory or intolerant to crizotinib, except
in cases of symptomatic systemic disease with an isolated lesion.18 The NCCN Central Nervous System
Cancers recommends brigatinib as a single-agent treatment for recurrent brain metastases
in patients with ALK-positive NSCLC.19
Enasidenib (Idhifa)
Enasidenib works by inhibiting the mutated IDH2 enzyme,
leading to decreased 2-hydroxyglutarate levels, reduced blast counts, and
increased myeloid differentiation and mature myeloid cells.
Indication
Enasidenib is approved for the treatment of relapsed or
refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2
(IDH2) mutation.20
Efficacy
Results from study AG221-C-001, a phase 1/2, open-label,
single-arm trial, led to the approval of enasidenib
for AML.20 Enasidenib 100 mg
daily was selected for the expansion phase of the study, which assessed
efficacy in 199 patients response rate
was 40.3%, and median DOR was 5.8 months. Median OS was 9.3 months (95% CI, 8.2
to 10.9 months), and 19.3% of patients attained a CR with a median overall
survival of 19.7 months (95% CI, 11.6 months to not reached).
Safety
The most common adverse events seen with enasidenib in the AG221-C-001 study were
hyperbilirubinemia and nausea.21
Hyperbilirubinemia, IDH differentiation syndrome, hematologic events, and
infections were the most common grade 3 or 4 events.
Guidelines
The NCCN AML guideline recommends enasidenib for patients
with relapsed or refractory AML with IDH2 mutation that are not candidates for
intensive remission induction therapy.22
Patients with a response to therapy, which may take 3 to 5 months, should continue
enasidenib therapy until progression occurs. The guideline also warns about the
increased risk of IDH differentiation syndrome and hyperleukocytosis that may
require treatment with hydroxyurea and steroids during treatment with
enasidenib.
Midostaurin (Rydapt)
Midostaurin inhibits several receptor tyrosine kinases such
as FLT3 mutant kinases, KIT, PDGFRα/β, VEGFR2, and PKC.23 The inhibition of FLT3 promotes
apoptosis of leukemic cells expressing FLT3 mutant kinases such as internal
tandem duplication (ITD) and tyrosine kinase domain (TKD) and leukemic cells
overexpressing wild type FLT3 and platelet-derived
growth factor (PDGF) receptors.
Indication
Midostaurin is indicated for newly diagnosed AML in patients
who are positive for FLT3 mutation.23 The medication is administered in
combination with cytarabine and daunorubicin induction and cytarabine
consolidation. Midostaurin is also approved for aggressive systemic
mastocytosis (ASM), systemic mastocytosis with associated
hematological neoplasm (SM-AHN), or mast cell leukemia.
Efficacy
Midostaurin was studied in a phase 3 trial that enrolled 717
patients with newly diagnosed AML and FLT3 mutation.24 Patients received induction therapy
with daunorubicin and cytarabine, consolidation therapy with high-dose
cytarabine, and midostaurin or placebo. From enrolled patients, 214 had high
ITD mutation, 341 low ITD mutation, and 162 point mutations in TKD. Median OS, the primary endpoint, was
prolonged in the midostaurin (74.7 months) group versus in the placebo (25.6 months)
group (hazard ratio for death, 0.78; 95% CI, 0.63 to 0.96; p=0.009).
Midostaurin was also studied in an open-label study in 116
patients, who had ASM, SM-AHN, or mast cell leukemia.25 Patients received midostaurin 100 mg
twice daily. The median OS was 28.7 months, and the median PFS was 14.1 months.
Safety
In the trial exploring midostaurin versus placebo use in
patients with newly diagnosed AML and FLT3 mutation, both groups displayed
similar adverse events except for higher rate of anemia and rash in the
midostaurin group and higher rate of nausea in the placebo group.24 From the trial of midostaurin in
patients with ASM, SM-AHN, or mast cell leukemia, the most common adverse
events were nausea, vomiting, and diarrhea.25
About 24% of patients developed grade 3 or 4 neutropenia, 41% grade 3 or 4
anemia, and 29% grade 3 or 4 thrombocytopenia.
Guidelines
Per the NCCN AML guideline, midostaurin is recommended as
induction therapy for FLT3 mutation-positive disease in combination with
standard dose cytarabine and daunorubicin as induction therapy. It is also
recommended as post-induction therapy or
post-remission therapy in combination with cytarabine.22 The US guidelines are lacking
for treatment of systemic mastocytosis.
Niraparib (Zejula)
Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor.26 PARP-1 and PARP-2 are enzymes involved
in DNA repair. Inhibition of PARP 1/2 increases formation of PARP-DNA
complexes, leading to DNA damage, apoptosis, and cell death.
Indication
Niraparib is approved as maintenance therapy for adults with
primary peritoneal cancer, recurrent epithelial ovarian cancer, or fallopian
tube cancer who have experienced CR or partial response to platinum-based
chemotherapy.26
Efficacy
Niraparib was approved based on the phase 3 NOVA trial.26 NOVA was a randomized, double-blind
trial comparing niraparib 300 mg daily
versus placebo in 553 patients with ovarian cancer, fallopian tube cancer, or
primary peritoneal cancer.27
All patients had previously received at least 2 platinum-based regimens and had
shown sensitivity to platinum-based treatment. Study treatment was started
within 8 weeks after the last dose of platinum-based therapy and was continued
until disease progression. Patients were categorized based on the presence or
absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort). In the gBRCA cohort, median PFS was 21.0 months
in the niraparib group versus 5.5 months
in the placebo group (hazard ratio, 0.27 0.26; 95% CI, 0.17 to 0.41). The non-gBRCA cohort had a median PFS of 9.3 months
with niraparib versus 3.9 months with
placebo (hazard ratio, 0.45; 95% CI, 0.34 to 0.61).
Safety
The most common grade 3 or 4 adverse events reported in the
NOVA trial for patients taking niraparib
were thrombocytopenia (33.8%), anemia (25.3%), and neutropenia (19.6%).27 Treatment discontinuation due to an
adverse event of any grade occurred in 14.7% of the niraparib group compared to only 2.2% of the placebo group.
Guidelines
The NCCN Ovarian Cancer guideline recommends niraparib as maintenance therapy for patients
with epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal
cancer who had previously received 2 or more platinum-based regimens and
demonstrated a CR or partial response.28
Neratinib (Nerlynx)
Neratinib
inhibits EGFR and HER2, demonstrating antitumor activity in cell lines
expressing these kinases.
Indication
Neratinib is
approved for use as extended adjuvant treatment following trastuzumab-based
therapy in patients with early-stage
HER2-positive breast cancer.29
Efficacy
Neratinib
was approved for HER2-positive breast cancer based on results from the ExteNET
trial.29 ExteNET was a
randomized, double-blind, phase 3 study assessing the safety and efficacy of
neratinib therapy versus placebo over 1 year in 2,840 women who previously
completed trastuzumab-based adjuvant therapy for early-stage HER2-positive
breast cancer.30 The invasive
disease-free survival rate was 93.9% 94.2% in the neratinib group versus 91.6%
91.9% in the placebo group at 2 years after randomization, with 5% of neratinib
patients experiencing invasive disease recurrence or death versus 8% of
patients in the placebo group (hazard ratio, 0.67 0.66; 95% CI, 0.50 0.49 to
0.91 0.90, p=0.0091 p=0.008).
Safety
The most common
grade 3 and 4 adverse events with neratinib in the ExteNET trial were diarrhea,
nausea, and vomiting.30 Rates
of QT prolongation were similar in the neratinib group (3%) and placebo group
(7%), and decreases in left ventricular ejection fraction occurred in only 1%
of each group. Four deaths occurred in the neratinib group and 3 in the placebo
group after study drug discontinuation, none of which were attributed to study
treatment.
Guidelines
The NCCN breast
cancer guideline recommends neratinib as extended adjuvant therapy for
HER2-positive patients after completion of adjuvant trastuzumab-based therapy
when there is a high risk of recurrence.10
Ribociclib (Kisqali)
Ribociclib is a CDK4 and CDK6 inhibitor.31 Enzymes CDK4 and 6 phosphorylate Rb leading to cell cycle
progression and cell proliferation. Ribociclib decreases phosphorylation of the
Rb and results in cell cycle arrest in the G1 phase.
Indication
Ribociclib is indicated in postmenopausal women with HR-positive,
HER2-negative advanced or metastatic breast cancer as initial endocrine-based
therapy in combination with an aromatase inhibitor.31
Efficacy
Ribociclib gained approval based on the results of the MONALEESA-2 trial.31 MONALEESA-2 was a
phase 3, double-blind, placebo-controlled trial.32 A total of 668 patients with HR-positive, HER2-negative
advanced breast cancer who had not received any previous systemic therapy were
enrolled in the trial. Patients were randomized to receive either ribociclib 600 mg daily for 21 days on and 7 days
off plus letrozole 2.5 mg daily continuously, or placebo plus letrozole. Median
PFS was not reached in the ribociclib
plus letrozole group, as compared to 14.7 months in the placebo plus letrozole
group. At 18 months, the estimated PFS was 63.0% (95% CI, 54.6 to 70.3) in the ribociclib group versus 42.2% (95% CI, 34.8 to
49.5) in the placebo group.
Safety
The most common grade 3 or 4 adverse events in the MONALEESA-2 trial were neutropenia (59.3% in
the ribociclib group versus 0.9% in the
placebo group), leukopenia (21% versus 0.6%), and hypertension (9.9% versus
10.9%).32 Discontinuation of
study drug due to adverse events occurred in 7.5% of the ribociclib group versus 2.1% of the placebo
group.
Guidelines
The NCCN Breast Cancer guideline recommends a CDK4/6
inhibitor (ribociclib or palbociclib) in
combination with an aromatase inhibitor as first-line treatment option for
postmenopausal patients with HR-positive, HER2-negative metastatic breast
cancer.10 Ribociclib in
addition to tamoxifen is another recommended therapy for this population.
Table 1. Key properties of newly approved oral
oncology agents in 2017.6,11,16,20,23,26,29,31,33
Drug name (Brand)
|
Dosage form,
strength(s)
|
Dosing
|
Costa
|
Abemaciclib
(Verzenio™)
|
Tablet; 50 mg, 100 mg, 150 mg, 200 mg
|
200 mg twice daily as monotherapy; 150 mg twice daily in
combination with fulvestrant 500 mg on Days 1, 15, 29, and then once monthly
|
$3,284
(14 tablets)
|
Acalabrutinib
(Calquence™)
|
Capsule; 100
mg
|
100 mg twice
daily
|
$16,877
(60 capsules)
|
Brigatinib
(Alunbrig™)
|
Tablet; 30
mg, 90 mg, 180 mg
|
90 mg daily
for 7 days, and then 180 mg daily if tolerated
|
$1,995
(21 tablets)
|
Enasidenib
(Idhifa™)
|
Tablet; 50 mg, 100 mg
|
100 mg daily
|
$29,846
(30 tablets)
|
Midostaurin
(Rydapt™)
|
Capsule; 25 mg
|
50 mg twice daily for AML; 100 mg twice daily for ASM,
SM-AHN, or mast cell leukemia
|
$4,497
(28 capsules)
|
Niraparib
(Zejula™)
|
Capsule; 100 mg
|
300 mg daily
|
$17,700
(90 capsules)
|
Neratinib
(Nerlynx™)
|
Tablet; 40 mg
|
240 mg daily
|
$12,600
(180 tablets)
|
Ribociclib
(Kisqali™)
|
Tablet; 200 mg
|
600 mg daily for 21 days, followed by 7 days off in
combination with continuous letrozole
|
$13,140
(63 tablets)
|
aPricing is based on average wholesale price.
Conclusion
In 2017, the FDA approved 8 new oral oncolytics with indications for AML, MCL, ASM, SM-AHN, mast cell
leukemia, NSCLC, breast cancer, peritoneal cancer, epithelial ovarian cancer,
or fallopian tube cancer. Pharmacists must be familiar with the efficacy and
safety data for these agents as a comprehensive counseling is imperative for
patients taking oral oncolytics. Patients
may inquire about the costs of these newly approved agents because higher
copays are more typical with oral oncolytics
compared to intravenous oncology medications.
References:
Heymach J, Krilov L, Alberg A, et al. Clinical cancer advances 2018: annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol. 2018;36(10):1020-1044.
McCullough S, Newton R. Pharmacy's changing role as care transitions from infused to oral therapies. Am J Manag Care. 2017;23(12 Spec No.):sp468.
Hematology/oncology (cancer) approvals & safety notifications. The Food and Drug Administration website. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm279174.htm. Updated March 22, 2018. Accessed March 26, 2018.
Bailey R, Newton R. PBMs: their role, the problems, and how practices can work with PBMs. Am J Manag Care. 2017;23(12 Spec No.):Sp497-sp498.
The state of cancer care in America, 2017: a report by the American Society of Clinical Oncology. J Oncol Pract. 2017;13(4):e353-e394.
Verzenio [package insert]. Indianapolis, IN: Eli Lilly and Company; 2018.
Dickler MN, Tolaney SM, Rugo HS, et al. MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 Inhibitor, as a single agent, in patients with refractory HR(+)/HER2(-) metastatic breast cancer. Clin Cancer Res. 2017;23(17):5218-5224.
Sledge GW, Jr., Toi M, Neven P, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017;35(25):2875-2884.
Goetz MP, Toi M, Campone M, et al. MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35(32):3638-3646.
NCCN Clinical Practice Guidelines in Oncology. Breast Cancer Version 1.2018. National Comprehensive Cancer Network website. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Published March 20, 2018. Accessed March 26, 2018.
Calquence [package insert]. Los Angeles, CA: Puma Biotechnology, Inc; 2017.
Wang M, Rule S, Zinzani P, et al. Abstract 155: Efficacy and safety of acalabrutinib monotherapy in patients with relapsed/refractory mantle cell lymphoma in the phase 2 ACE-LY-004 study. 2017 ASH Meeting. Available at: http://www.bloodjournal.org/content/130/Suppl_1/155. Accessed May 29, 2018.
Imbruvica [package insert]. Sunnyvale, CA: Pharmacyclics LLC; 2017.
NCCN Clinical Practice Guidelines in Oncology. B-Cell Lymphomas Version 2.2018. National Comprehensive Cancer Network website. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf. Published February 26, 2018. Accessed March 26, 2018.
NCCN Clinical Practice Guidelines in Oncology. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Version 5.2018. National Comprehensive Cancer Network website. https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf. Published March 26, 2018. Accessed April 11, 2018.
Alunbrig [package insert]. Cambridge, MA: Ariad Pharmaceuticals, Inc; 2018.
Camidge DR, Tiseo M, Ahn MJ, et al. Brigatinib in crizotinib-refractory ALK+ NSCLC: central assessment and updates from ALTA, a pivotal randomized phase 2 trial. J Thorac Oncol. 2016;12(1 suppl) [abstract P3.02a-013].
NCCN Clinical Practice Guidelines in Oncology. Non-Small Cell Lung Cancer Version 3.2018. National Comprehensive Cancer Network website. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Published February 21, 2018. Accessed March 26, 2018.
NCCN Clinical Practice Guidelines in Oncology. Central Nervous System Cancers Version 1.2018. National Comprehensive Cancer Network website. https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf. Published March 20, 2018. Accessed April 11, 2018.
Idhifa [package insert]. Summit, NJ: Celgene Corporation; 2017.
Stein EM, DiNardo CD, Pollyea DA, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017;130(6):722-731.
NCCN Clinical Practice Guidelines in Oncology. Acute Myeloid Leukemia Version 1.2018. National Comprehensive Cancer Network website. https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Published February 7, 2018. Accessed March 26, 2018.
Rydapt [package insert]. East Hanover, NJ: Novartis; 2017.
Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017;377(5):454-464.
Gotlib J, Kluin-Nelemans HC, George TI, et al. Efficacy and safety of midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016;374(26):2530-2541.
Zejula [package insert]. Waltham, MA: Tesaro, Inc.; 2018.
Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016;375(22):2154-2164.
NCCN Clinical Practice Guidelines in Oncology. Ovarian Cancer Version 2.2018. National Comprehensive Cancer Network website. https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf. Published March 9, 2018. Accessed March 26, 2018.
Nerlynx [package insert]. Los Angeles, CA: Puma Biotechnology, Inc; 2017.
Chan A, Delaloge S, Holmes FA, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17(3):367-377.
Kisqali [package insert]. East Hanover, NJ: Novartis; 2017.
Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738-1748.
LexiComp [database]. Hudson, OH: Wolters Kluwer Health; 2018. https://online.lexi.com/lco/action/home. Accessed March 26, 2018