LORBRENA treatment resulted in 72% reduction in
risk of progression or death
Data also show secondary endpoint of
intra-cranial response substantially improved with LORBRENA
Pfizer Inc. (NYSE:PFE) today announced results from the Phase 3
CROWN trial of LORBRENA® (lorlatinib, available in Europe under the
brand name LORVIQUA®) versus XALKORI® (crizotinib) in people with
previously untreated anaplastic lymphoma kinase (ALK)-positive
advanced non-small cell lung cancer (NSCLC) were published online
ahead of print in the New England Journal of Medicine. At a planned
interim analysis, LORBRENA treatment resulted in statistically
significant and clinically meaningful improvement in
progression-free survival (PFS) according to blinded independent
central review (BICR), the primary endpoint, compared to XALKORI
(HR 0.28: 95% CI, 0.19 to 0.41; p<0.001), corresponding to a 72%
reduction in the risk of progression or death. The trial is
continuing for the secondary endpoint of overall survival (OS),
which was not mature at the time of analysis.
“For nearly a decade, we have been committed to transforming the
treatment of non-small cell lung cancer through the development of
innovative medicines like LORBRENA, a third-generation
ALK-inhibitor specifically developed to inhibit the most common
tumor mutations that drive resistance to current medications and to
address brain metastases,” said Chris Boshoff, M.D., Ph.D., Chief
Development Officer, Oncology, Pfizer Global Product Development.
“The prolonged progression-free survival data and intracranial
responses seen in the CROWN trial highlight the potential role for
LORBRENA to significantly improve outcomes for people with
previously untreated ALK-positive advanced NSCLC and we are pleased
that these data will be reviewed as part of the FDA’s Real-Time
Oncology Review (RTOR) pilot program.”
As a secondary endpoint, the confirmed objective response rate
(ORR) was 76% (95% CI, 68 to 83) with LORBRENA and 58% (95% CI, 49
to 66) with XALKORI. Additionally, LORBRENA showed increased
intracranial activity compared with XALKORI. In the LORBRENA arm,
96% (95% CI, 91 to 98) of people were without central nervous
system (CNS) progression at 12 months compared to 60% (95% CI, 49
to 69) in the XALKORI arm (HR 0.07: 95% CI, 0.03 to 0.17). In
people presenting with measurable brain metastases (n=30), the
intracranial ORR was 82% (95% CI, 57 to 96, n=14) with LORBRENA and
23% (95% CI, 5 to 54, n=3) with XALKORI; intracranial complete
response rates of 71% and 8% were seen in each arm,
respectively.
“Biomarker-driven medicines have improved outcomes for people
living with ALK-positive non-small cell lung cancer, but innovative
therapies are still needed to delay disease progression,” said
Benjamin Solomon, M.D., Department of Medical Oncology, Peter
MacCallum Cancer Centre. “The results from the CROWN trial
demonstrate that LORBRENA has the potential to be a
practice-changing, first-line option, and we thank the many people
and their families who participated in this trial.”
In this trial, adverse events (AEs) occurring in >20% of
patients treated with LORBRENA were hypercholesterolemia (70%),
hypertriglyceridemia (64%), edema (55%), weight increase (38%),
peripheral neuropathy (34%), cognitive effects (21%), and diarrhea
(21%). Grade 3 or 4 AEs occurred in 72% of people treated with
LORBRENA and 56% of people treated with XALKORI. The most common
Grade 3 or 4 AEs for LORBRENA were hypertriglyceridemia (20%),
increased weight (17%), hypercholesterolemia (16%), and
hypertension (10%). Adverse events leading to permanent treatment
discontinuation occurred in 7% of people treated with LORBRENA and
9% of people treated with XALKORI.
CROWN is a global, Phase 3, randomized, open-label, parallel
2-arm trial in which 296 people with previously untreated
ALK-positive advanced NSCLC were randomized 1:1 to receive LORBRENA
monotherapy (n=149) or XALKORI monotherapy (n=147). The primary
endpoint of the CROWN trial is PFS based on BICR. Secondary
endpoints include PFS based on investigator’s assessment, OS, ORR,
intracranial objective response, and safety.
In 2018, the Food and Drug Administration (FDA) approved
LORBRENA for the treatment of patients with ALK-positive metastatic
NSCLC whose disease has progressed on crizotinib and at least one
other ALK inhibitor for metastatic disease; or whose disease has
progressed on alectinib or ceritinib as the first ALK inhibitor
therapy for metastatic disease. This indication is approved under
accelerated approval based on tumor response rate and duration of
response. CROWN is the confirmatory trial for the conversion to
full approval. Based on the positive outcome of the CROWN trial,
the data will be reviewed under the FDA’s Real Time Oncology Review
pilot program and will be shared with other health authorities to
seek approval for an indication that includes previously untreated
ALK-positive advanced NSCLC.
Lung cancer is the number one cause of cancer-related death
around the world.1 NSCLC accounts for approximately 80-85% of lung
cancers,2 with ALK-positive tumors occurring in about 3-5% of NSCLC
cases.3 In 2020, an estimated 13,000 new cases of ALK-positive
NSCLC are expected to be diagnosed in the G7.4
About LORBRENA® (lorlatinib)
LORBRENA is a tyrosine kinase inhibitor (TKI) that has been
shown to be highly active in preclinical lung cancer models
harboring chromosomal rearrangements of ALK. LORBRENA was
specifically developed to inhibit tumor mutations that drive
resistance to other ALK inhibitors and to penetrate the blood brain
barrier. LORBRENA is approved in the U.S. for the treatment of
patients with ALK-positive metastatic NSCLC whose disease has
progressed on:
- crizotinib and at least one other ALK inhibitor for metastatic
disease; or
- alectinib as the first ALK inhibitor therapy for metastatic
disease; or
- ceritinib as the first ALK inhibitor therapy for metastatic
disease.
- This indication is approved under accelerated approval based on
tumor response rate and duration of response. Continued approval
for this indication may be contingent upon verification and
description of clinical benefit in a confirmatory trial.
The full prescribing information for LORBRENA can be found
here.
IMPORTANT LORBRENA® (lorlatinib) SAFETY INFORMATION FROM THE
U.S. PRESCRIBING INFORMATION
Contraindications: LORBRENA is contraindicated in
patients taking strong CYP3A inducers, due to the potential for
serious hepatotoxicity.
Risk of Serious Hepatotoxicity with Concomitant Use of Strong
CYP3A Inducers: Severe hepatotoxicity occurred in 10 of 12
healthy subjects receiving a single dose of LORBRENA with multiple
daily doses of rifampin, a strong CYP3A inducer. Grade 4 ALT or AST
elevations occurred in 50% of subjects, Grade 3 in 33% of subjects,
and Grade 2 in 8% of subjects. ALT or AST elevations occurred
within 3 days and returned to within normal limits after a median
of 15 days (7 to 34 days); median time to recovery in subjects with
Grade 3 or 4 or Grade 2 ALT or AST elevations was 18 days and 7
days, respectively. Discontinue strong CYP3A inducers for 3 plasma
half-lives of the strong CYP3A inducer prior to initiating
LORBRENA. Avoid concomitant use of LORBRENA with moderate CYP3A
inducers. If concomitant use of moderate CYP3A inducers cannot be
avoided, monitor AST, ALT, and bilirubin 48 hours after initiating
LORBRENA and at least 3 times during the first week after
initiating LORBRENA. Depending upon the relative importance of each
drug, discontinue LORBRENA or the CYP3A inducer for persistent
Grade 2 or higher hepatotoxicity.
Central Nervous System (CNS) Effects: A broad spectrum of
CNS effects can occur; overall, CNS effects occurred in 54% of 332
patients receiving LORBRENA. These included seizures (3%, sometimes
in conjunction with other neurologic findings), hallucinations (7%;
0.6% severe [Grade 3 or 4]), and changes in cognitive function
(29%; 2.1% severe), mood (including suicidal ideation) (24%; 1.8%
severe), speech (14%; 0.3% severe), mental status (2.1%; 1.8%
severe), and sleep (10%). Median time to first onset of any CNS
effect was 1.2 months (1 day to 1.7 years). Overall, 1.5% and 9% of
patients required permanent or temporary discontinuation of
LORBRENA, respectively, for a CNS effect; 8% required dose
reduction. Withhold and resume at same or reduced dose or
permanently discontinue based on severity.
Hyperlipidemia: Increases in serum cholesterol and
triglycerides can occur. Grade 3 or 4 elevations in total
cholesterol occurred in 17% and Grade 3 or 4 elevations in
triglycerides occurred in 17% of the 332 patients who received
LORBRENA. Median time to onset was 15 days for both
hypercholesterolemia and hypertriglyceridemia. Approximately 7% and
3% of patients required temporary discontinuation or dose reduction
of LORBRENA, respectively, for elevations in cholesterol and in
triglycerides. Eighty percent of patients required initiation of
lipid-lowering medications, with a median time to onset of start of
such medications of 21 days. Initiate or increase the dose of
lipid-lowering agents in patients with hyperlipidemia. Monitor
serum cholesterol and triglycerides before initiating LORBRENA, 1
and 2 months after initiating LORBRENA, and periodically
thereafter. Withhold and resume at same dose for the first
occurrence; resume at same or reduced dose of LORBRENA for
recurrence based on severity.
Atrioventricular (AV) Block: PR interval prolongation and
AV block can occur. In 295 patients who received LORBRENA at a dose
of 100 mg orally once daily and who had a baseline
electrocardiography (ECG), 1% experienced AV block and 0.3%
experienced Grade 3 AV block and underwent pacemaker placement.
Monitor ECG prior to initiating LORBRENA and periodically
thereafter. Withhold and resume at reduced or same dose in patients
who undergo pacemaker placement. Permanently discontinue for
recurrence in patients without a pacemaker.
Interstitial Lung Disease (ILD)/Pneumonitis: Severe or
life-threatening pulmonary adverse reactions consistent with
ILD/pneumonitis can occur. ILD/pneumonitis occurred in 1.5% of
patients, including Grade 3 or 4 ILD/pneumonitis in 1.2% of
patients. One patient (0.3%) discontinued LORBRENA for
ILD/pneumonitis. Promptly investigate for ILD/pneumonitis in any
patient who presents with worsening of respiratory symptoms
indicative of ILD/pneumonitis. Immediately withhold LORBRENA in
patients with suspected ILD/pneumonitis. Permanently discontinue
LORBRENA for treatment-related ILD/pneumonitis of any severity.
Embryo-fetal Toxicity: LORBRENA can cause fetal harm.
Advise pregnant women of the potential risk to a fetus. Advise
females of reproductive potential to use an effective non-hormonal
method of contraception, since LORBRENA can render hormonal
contraceptives ineffective, during treatment with LORBRENA and for
at least 6 months after the final dose. Advise males with female
partners of reproductive potential to use effective contraception
during treatment with LORBRENA and for 3 months after the final
dose.
Adverse Reactions: Serious adverse reactions occurred in
32% of the 295 patients; the most frequently reported serious
adverse reactions were pneumonia (3.4%), dyspnea (2.7%), pyrexia
(2%), mental status changes (1.4%), and respiratory failure (1.4%).
Fatal adverse reactions occurred in 2.7% of patients and included
pneumonia (0.7%), myocardial infarction (0.7%), acute pulmonary
edema (0.3%), embolism (0.3%), peripheral artery occlusion (0.3%),
and respiratory distress (0.3%). The most common (≥20%) adverse
reactions were (all Grades; Grade 3 or 4): edema (57%; 3.1%),
peripheral neuropathy (47%; 2.7%), cognitive effects (27%; 2.0%),
dyspnea (27%; 5.4%), fatigue (26%; 0.3%), weight gain (24%; 4.4%),
arthralgia (23%; 0.7%), mood effects (23%; 1.7%), and diarrhea
(22%; 0.7%); the most common (≥20%) laboratory abnormalities were
(all Grades; Grade 3 or 4): hypercholesterolemia (96%; 18%),
hypertriglyceridemia (90%; 18%), anemia (52%; 4.8%), hyperglycemia
(52%; 5%), increased AST (37%; 2.1%), hypoalbuminemia (33%; 1.0%),
increased ALT (28%; 2.1%), increased lipase (24%; 10%), and
increased alkaline phosphatase (24%; 1.0%).
Drug Interactions: LORBRENA is contraindicated in patients
taking strong CYP3A inducers. Avoid concomitant use with moderate
CYP3A inducers and strong CYP3A inhibitors. If concomitant use of
moderate CYP3A inducers cannot be avoided, monitor ALT, AST, and
bilirubin as recommended. If concomitant use with a strong CYP3A
inhibitor cannot be avoided, reduce the LORBRENA dose as
recommended. Avoid concomitant use of LORBRENA with CYP3A
substrates and P-gp substrates, which may reduce the efficacy of
these substrates.
Lactation: Because of the potential for serious adverse
reactions in breastfed infants, instruct women not to breastfeed
during treatment with LORBRENA and for 7 days after the final
dose.
Hepatic Impairment: No dose adjustment is recommended for
patients with mild hepatic impairment. The recommended dose of
LORBRENA has not been established for patients with moderate or
severe hepatic impairment.
Renal Impairment: No dose adjustment is recommended for
patients with mild or moderate renal impairment. The recommended
dose of LORBRENA has not been established for patients with severe
renal impairment.
About XALKORI® (crizotinib)
XALKORI is a TKI indicated for the treatment of patients with
metastatic NSCLC whose tumors are ALK- or ROS1-positive as detected
by an FDA-approved test. XALKORI has received approval for patients
with ALK-positive NSCLC in more than 90 countries including
Australia, Canada, China, Japan, South Korea and the European
Union. XALKORI is also approved for ROS1-positive NSCLC in more
than 60 countries.
The full prescribing information for XALKORI can be found
here.
IMPORTANT XALKORI® (crizotinib) SAFETY INFORMATION FROM THE
U.S. PRESCRIBING INFORMATION
Hepatotoxicity: Drug-induced hepatotoxicity with fatal
outcome occurred in 0.1% of patients treated with XALKORI across
clinical trials (n=1719). Increased transaminases generally
occurred within the first 2 months. Monitor liver function tests,
including ALT, AST, and total bilirubin, every 2 weeks during the
first 2 months of treatment, then once a month, and as clinically
indicated, with more frequent repeat testing for increased liver
transaminases, alkaline phosphatase, or total bilirubin in patients
who develop increased transaminases. Permanently discontinue for
ALT/AST elevation >3 times ULN with concurrent total bilirubin
elevation >1.5 times ULN (in the absence of cholestasis or
hemolysis); otherwise, temporarily suspend and dose-reduce XALKORI
as indicated.
Interstitial Lung Disease/Pneumonitis: Severe,
life-threatening, or fatal interstitial lung disease
(ILD)/pneumonitis can occur. Across clinical trials (n=1719), 2.9%
of XALKORI-treated patients had any grade ILD, 1.0% had Grade 3/4,
and 0.5% had fatal ILD. ILD generally occurred within 3 months
after initiation of treatment. Monitor for pulmonary symptoms
indicative of ILD/pneumonitis. Exclude other potential causes and
permanently discontinue XALKORI in patients with drug-related
ILD/pneumonitis.
QT Interval Prolongation: QTc prolongation can occur.
Across clinical trials (n=1616), 2.1% of patients had QTcF
(corrected QT by the Fridericia method) ≥500 ms and 5% of 1582
patients had an increase from baseline QTcF ≥60 ms by automated
machine-read evaluation of ECGs. Avoid use in patients with
congenital long QT syndrome. Monitor ECGs and electrolytes in
patients with congestive heart failure, bradyarrhythmias,
electrolyte abnormalities, or who are taking medications that
prolong the QT interval. Permanently discontinue XALKORI in
patients who develop QTc >500 ms or ≥60 ms change from baseline
with Torsade de pointes, polymorphic ventricular tachycardia, or
signs/symptoms of serious arrhythmia. Withhold XALKORI in patients
who develop QTc >500 ms on at least 2 separate ECGs until
recovery to a QTc ≤480 ms, then resume at next lower dosage.
Bradycardia: Symptomatic bradycardia can occur. Across
clinical trials, bradycardia occurred in 13% of patients treated
with XALKORI (n=1719). Avoid use in combination with other
medications known to cause bradycardia. Monitor heart rate and
blood pressure regularly. If bradycardia occurs, re-evaluate for
the use of concomitant medications known to cause bradycardia.
Permanently discontinue for life-threatening bradycardia due to
XALKORI; however, if associated with concomitant medications known
to cause bradycardia or hypotension, hold XALKORI until recovery to
asymptomatic bradycardia or to a heart rate of ≥60 bpm. If
concomitant medications can be adjusted or discontinued, restart
XALKORI at 250 mg once daily with frequent monitoring.
Severe Visual Loss: Across clinical trials, the incidence
of Grade 4 visual field defect with vision loss was 0.2% of 1719
patients. Discontinue XALKORI in patients with new onset of severe
visual loss (best corrected vision less than 20/200 in one or both
eyes). Perform an ophthalmological evaluation. There is
insufficient information to characterize the risks of resumption of
XALKORI in patients with a severe visual loss; a decision to resume
should consider the potential benefits to the patient.
Vision Disorders: Most commonly visual impairment,
photopsia, blurred vision or vitreous floaters, occurred in 63% of
1719 patients. The majority (95%) of these patients had Grade 1
visual adverse reactions. 0.8% of patients had Grade 3 and 0.2% had
Grade 4 visual impairment. The majority of patients on the XALKORI
arms in Studies 1 and 2 (>50%) reported visual disturbances
which occurred at a frequency of 4-7 days each week, lasted up to 1
minute, and had mild or no impact on daily activities.
Embryo-Fetal Toxicity: XALKORI can cause fetal harm when
administered to a pregnant woman. Advise of the potential risk to
the fetus. Advise females of reproductive potential and males with
female partners of reproductive potential to use effective
contraception during treatment and for at least 45 days (females)
or 90 days (males) respectively, following the final dose of
XALKORI.
ROS1-positive Metastatic NSCLC: Safety was evaluated in
50 patients with ROS1-positive metastatic NSCLC from a single-arm
study, and was generally consistent with the safety profile of
XALKORI evaluated in patients with ALK-positive metastatic NSCLC.
Vision disorders occurred in 92% of patients in the ROS1 study; 90%
of patients had Grade 1 vision disorders and 2% had Grade 2.
Adverse Reactions: Safety was evaluated in a phase 3
study in previously untreated patients with ALK-positive metastatic
NSCLC randomized to XALKORI (n=171) or chemotherapy (n=169).
Serious adverse events were reported in 34% of patients treated
with XALKORI, the most frequent were dyspnea (4.1%) and pulmonary
embolism (2.9%). Fatal adverse events in XALKORI-treated patients
occurred in 2.3% of patients, consisting of septic shock, acute
respiratory failure, and diabetic ketoacidosis. Common adverse
reactions (all grades) occurring in ≥25% and more commonly (≥5%) in
patients treated with XALKORI vs chemotherapy were vision disorder
(71% vs 10%), diarrhea (61% vs 13%), edema (49% vs 12%), vomiting
(46% vs 36%), constipation (43% vs 30%), upper respiratory
infection (32% vs 12%), dysgeusia (26% vs 5%), and abdominal pain
(26% vs 12%). Grade 3/4 reactions occurring at a ≥2% higher
incidence with XALKORI vs chemotherapy were QT prolongation (2% vs
0%), esophagitis (2% vs 0%), and constipation (2% vs 0%). In
patients treated with XALKORI vs chemotherapy, the following
occurred: elevation of ALT (any grade [79% vs 33%] or Grade 3/4
[15% vs 2%]); elevation of AST (any grade [66% vs 28%] or Grade 3/4
[8% vs 1%]); neutropenia (any grade [52% vs 59%] or Grade 3/4 [11%
vs 16%]); lymphopenia (any grade [48% vs 53%] or Grade 3/4 [7% vs
13%]); hypophosphatemia (any grade [32% vs 21%] or Grade 3/4 [10%
vs 6%]). In patients treated with XALKORI vs chemotherapy, renal
cysts occurred (5% vs 1%). Nausea (56%), decreased appetite (30%),
fatigue (29%), and neuropathy (21%) also occurred in patients
taking XALKORI.
Drug Interactions: Use caution with concomitant use of
moderate CYP3A inhibitors. Avoid grapefruit or grapefruit juice
which may increase plasma concentrations of crizotinib. Avoid
concomitant use of strong CYP3A inducers and inhibitors. Avoid
concomitant use of CYP3A substrates where minimal concentration
changes may lead to serious adverse reactions. If concomitant use
of XALKORI is unavoidable, decrease the CYP3A substrate dosage in
accordance with approved product labeling.
Lactation: Because of the potential for adverse reactions
in breastfed children, advise women not to breastfeed during
treatment with XALKORI and for 45 days after the final dose.
Hepatic Impairment: Crizotinib concentrations increased
in patients with pre-existing moderate (any AST and total bilirubin
>1.5x ULN and ≤3x ULN) or severe (any AST and total bilirubin
>3x ULN) hepatic impairment. Reduce XALKORI dosage in patients
with moderate or severe hepatic impairment. The recommended dose of
XALKORI in patients with pre-existing moderate hepatic impairment
is 200 mg orally twice daily or with pre-existing severe hepatic
impairment is 250 mg orally once daily.
Renal Impairment: Decreases in estimated glomerular
filtration rate occurred in patients treated with XALKORI.
Administer XALKORI at a starting dose of 250 mg taken orally once
daily in patients with severe renal impairment (CLcr <30 mL/min)
not requiring dialysis.
About Pfizer Oncology
At Pfizer Oncology, we are committed to advancing medicines
wherever we believe we can make a meaningful difference in the
lives of people living with cancer. Today, we have an
industry-leading portfolio of 23 approved innovative cancer
medicines and biosimilars across more than 30 indications,
including breast, genitourinary, colorectal, blood and lung
cancers, as well as melanoma.
Pfizer Inc.: Breakthroughs that change patients’
lives
At Pfizer, we apply science and our global resources to bring
therapies to people that extend and significantly improve their
lives. We strive to set the standard for quality, safety and value
in the discovery, development and manufacture of health care
products, including innovative medicines and vaccines. Every day,
Pfizer colleagues work across developed and emerging markets to
advance wellness, prevention, treatments and cures that challenge
the most feared diseases of our time. Consistent with our
responsibility as one of the world's premier innovative
biopharmaceutical companies, we collaborate with health care
providers, governments and local communities to support and expand
access to reliable, affordable health care around the world. For
more than 150 years, we have worked to make a difference for all
who rely on us. We routinely post information that may be important
to investors on our website at www.pfizer.com. In addition, to
learn more, please visit us on www.pfizer.com and follow us on
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DISCLOSURE NOTICE: The information contained in this release is
as of November 19, 2020. Pfizer assumes no obligation to update
forward-looking statements contained in this release as the result
of new information or future events or developments.
This release contains forward-looking information about
LORBRENA® (lorlatinib), including its potential benefits, that
involves substantial risks and uncertainties that could cause
actual results to differ materially from those expressed or implied
by such statements. Risks and uncertainties include, among other
things, uncertainties regarding the commercial success of LORBRENA;
the uncertainties inherent in research and development, including
the ability to meet anticipated clinical endpoints, commencement
and/or completion dates for our clinical trials, regulatory
submission dates, regulatory approval dates and/or launch dates, as
well as the possibility of unfavorable new clinical data and
further analyses of existing clinical data; the risk that clinical
trial data are subject to differing interpretations and assessments
by regulatory authorities; whether regulatory authorities will be
satisfied with the design of and results from our clinical studies;
whether and when any drug applications may be filed in any
additional jurisdictions for LORBRENA for treatment of patients
with ALK-positive metastatic non-small cell lung cancer or in any
jurisdictions for any other potential indications for LORBRENA;
whether and when any such other applications may be approved by
regulatory authorities, which will depend on a myriad factors,
including making a determination as to whether the product's
benefits outweigh its known risks and determination of the
product's efficacy and, if approved, whether such product candidate
will be commercially successful; decisions by regulatory
authorities impacting labeling, manufacturing processes, safety
and/or other matters that could affect the availability or
commercial potential of LORBRENA; uncertainties regarding the
impact of COVID-19 on Pfizer’s business, operations and financial
results and competitive developments.
A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended
December 31, 2019 and in its subsequent reports on Form 10-Q,
including in the sections thereof captioned “Risk Factors” and
“Forward-Looking Information and Factors That May Affect Future
Results,” as well as in its subsequent reports on Form 8-K, all of
which are filed with the U.S. Securities and Exchange Commission
and available at www.sec.gov and www.pfizer.com.
__________________ 1 World Health Organization. International
Agency for Research on Cancer. GLOBOCAN 2018: Lung fact sheet.
http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf.
Accessed November 2020. 2 American Cancer Society. What is lung
cancer?
https://www.cancer.org/cancer/lung-cancer/about/what-is.html.
Accessed November 2020. 3 Garber K. ALK, lung cancer, and
personalized therapy: portent of the future? J Natl Cancer Inst.
2010;102:672-675. 4 Decision Resource Group, Kantar Health.
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