Four-week dosing now approved in all
IMFINZI indications, reducing medical visits and improving
patient convenience
AstraZeneca’s IMFINZI® (durvalumab) has been approved in the US
for an additional dosing option, a 1,500mg fixed dose every four
weeks, in the approved indications of unresectable Stage III
non-small cell lung cancer (NSCLC) after chemoradiation therapy
(CRT) and previously treated advanced bladder cancer. This new
option is consistent with the approved IMFINZI dosing in
extensive-stage small cell lung cancer (ES-SCLC) and will be
available to patients weighing more than 30kg as an alternative to
the approved weight-based dosing of 10mg/kg every two weeks.
The approval by the Food and Drug Administration (FDA) was based
on data from several IMFINZI clinical trials, including the PACIFIC
Phase III trial which supported the two-week, weight-based dosing
in unresectable Stage III NSCLC, and the CASPIAN Phase III trial
which used four-week, fixed-dosing during maintenance treatment in
ES-SCLC. The decision follows the Priority Review granted by the
FDA in August 2020.
Victoria M. Villaflor, MD, Clinical Professor in the Department
of Medical Oncology and Therapeutics Research at City of Hope
Cancer Center, Los Angeles, California, said: “This new four-week
dosing option gives doctors the choice to cut the number of visits
for critical cancer treatment in half and offers a regimen that is
more convenient for patients. Additionally, it limits potential
exposure to infection in the healthcare environment for a
population that is especially vulnerable to complications from
COVID-19.”
Dave Fredrickson, Executive Vice President, Oncology Business
Unit, said: “The approval of this new dosing option across
indications reflects our ongoing commitment to improve the patient
experience and ensure continuity of care - a priority at all times,
but especially during the pandemic. Cancer won’t wait, and it is
our job to provide patients with treatment options that acknowledge
the challenges the pandemic poses to cancer care, enabling them to
visit their physician when truly needed and avoid preventable
exposure to healthcare-associated infections.”
The four-week 1,500mg fixed-dosing option for IMFINZI is also
under regulatory review in several other countries, including in
the EU where the new dosing option was granted accelerated
assessment.
IMFINZI is approved in the curative-intent setting of
unresectable, Stage III NSCLC after CRT in the US, in the EU, in
Japan, in China and in many other countries, based on the PACIFIC
Phase III trial. IMFINZI is also approved for previously treated
patients with advanced bladder cancer in the US and several other
countries. Additionally, it is approved in the US, the EU, Japan
and several other countries around the world for the treatment of
ES-SCLC based on the CASPIAN Phase III trial.
Important Safety Information There are no
contraindications for IMFINZI® (durvalumab).
Immune-Mediated Adverse Reactions Important
immune-mediated adverse reactions listed under Warnings and
Precautions may not include all possible severe and fatal
immune-mediated reactions. Immune-mediated adverse reactions, which
may be severe or fatal, can occur in any organ system or tissue.
Immune-mediated adverse reactions can occur at any time after
starting treatment or after discontinuation. Monitor patients
closely for symptoms and signs that may be clinical manifestations
of underlying immune-mediated adverse reactions. Evaluate liver
enzymes, creatinine, and thyroid function at baseline and
periodically during treatment. In cases of suspected
immune-mediated adverse reactions, initiate appropriate workup to
exclude alternative etiologies, including infection. Institute
medical management promptly, including specialty consultation as
appropriate. Withhold or permanently discontinue IMFINZI depending
on severity. See Dosing and Administration for specific details. In
general, if IMFINZI requires interruption or discontinuation,
administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day
prednisone or equivalent) until improvement to Grade 1 or less.
Upon improvement to Grade 1 or less, initiate corticosteroid taper
and continue to taper over at least 1 month. Consider
administration of other systemic immunosuppressants in patients
whose immune-mediated adverse reactions are not controlled with
corticosteroid therapy.
Immune-Mediated Pneumonitis
IMFINZI can cause immune-mediated pneumonitis. The incidence of
pneumonitis is higher in patients who have received prior thoracic
radiation. In patients who did not receive recent prior radiation,
the incidence of immune-mediated pneumonitis was 2.0% (28/1414),
including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions.
In patients who received recent prior radiation, the incidence of
pneumonitis (including radiation pneumonitis) in patients with
unresectable Stage III NSCLC following definitive chemoradiation
within 42 days prior to initiation of IMFINZI in PACIFIC was 16.6%
(79/475) in patients receiving IMFINZI and 13.2% (31/234) in
patients receiving placebo. Of the 79 patients who received
IMFINZI, 1.1% were fatal and 2.5% were Grade 3-4 adverse reactions.
The frequency and severity of immune-mediated pneumonitis in
patients who did not receive definitive chemoradiation prior to
IMFINZI were similar in patients who received IMFINZI as a single
agent or with ES-SCLC when in combination with chemotherapy.
Immune-Mediated Colitis
IMFINZI can cause immune-mediated colitis that is frequently
associated with diarrhea. Cytomegalovirus (CMV)
infection/reactivation has been reported in patients with
corticosteroid-refractory immune-mediated colitis. In cases of
corticosteroid-refractory colitis, consider repeating infectious
workup to exclude alternative etiologies. Immune-mediated colitis
occurred in 1.6% (31/1889) of patients receiving IMFINZI, including
Grade 4 (0.1%) and Grade 3 (0.3%) adverse reactions.
Immune-Mediated Hepatitis
IMFINZI can cause immune-mediated hepatitis. Immune-mediated
hepatitis occurred in 1.0% (19/1889) of patients receiving IMFINZI,
including fatal (<0.1%) and Grade 3 (0.6%) adverse
reactions.
Immune-Mediated
Endocrinopathies
- Adrenal Insufficiency: IMFINZI can cause primary or
secondary adrenal insufficiency. For Grade 2 or higher adrenal
insufficiency, initiate symptomatic treatment, including hormone
replacement as clinically indicated. Immune-mediated adrenal
insufficiency occurred in 0.4% (7/1889) of patients receiving
IMFINZI, including Grade 3 (<0.1%) adverse reactions.
- Hypophysitis: IMFINZI can cause immune-mediated
hypophysitis. Hypophysitis can present with acute symptoms
associated with mass effect such as headache, photophobia, or
visual field cuts. Hypophysitis can cause hypopituitarism. Initiate
symptomatic treatment including hormone replacement as clinically
indicated. Grade 3 hypophysitis/hypopituitarism occurred in
<0.1% (1/1889) of patients who received IMFINZI.
- Thyroid Disorders: IMFINZI can cause immune-mediated
thyroid disorders. Thyroiditis can present with or without
endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate
hormone replacement therapy for hypothyroidism or institute medical
management of hyperthyroidism as clinically indicated.
- Thyroiditis: Immune-mediated thyroiditis occurred in
0.4% (7/1889) of patients receiving IMFINZI.
- Hyperthyroidism: Immune-mediated hyperthyroidism
occurred in 1.4% (27/1889) of patients receiving IMFINZI.
- Hypothyroidism: Immune-mediated hypothyroidism occurred
in 7.3% (137/1889) of patients receiving IMFINZI, including Grade 3
(<0.1%) adverse reactions.
- Type 1 Diabetes Mellitus, which can present with diabetic
ketoacidosis: Monitor patients for hyperglycemia or other signs
and symptoms of diabetes. Initiate treatment with insulin as
clinically indicated. Grade 3 immune-mediated type 1 diabetes
mellitus occurred in <0.1% (1/1889) of patients receiving
IMFINZI.
Immune-Mediated Nephritis with Renal
Dysfunction IMFINZI can cause immune-mediated nephritis.
Immune-mediated nephritis occurred in 0.3% (5/1889) of patients
receiving IMFINZI, including Grade 3 (0.1%) adverse reactions.
Immune-Mediated Dermatology
Reactions IMFINZI can cause immune-mediated rash or
dermatitis. Exfoliative dermatitis, including Stevens Johnson
Syndrome (SJS), drug rash with eosinophilia and systemic symptoms
(DRESS), and toxic epidermal necrolysis (TEN), have occurred with
PD-1/L-1 blocking antibodies. Topical emollients and/or topical
corticosteroids may be adequate to treat mild to moderate
non-exfoliative rashes. Immune-mediated rash or dermatitis occurred
in 1.6% (30/1889) of patients receiving IMFINZI, including Grade 3
(0.4%) adverse reactions.
Other Immune-Mediated Adverse
Reactions The following clinically significant,
immune-mediated adverse reactions occurred at an incidence of less
than 1% each in patients who received IMFINZI or were reported with
the use of other PD-1/PD-L1 blocking antibodies.
- Cardiac/vascular: Myocarditis, pericarditis,
vasculitis.
- Nervous system: Meningitis, encephalitis, myelitis and
demyelination, myasthenic syndrome/myasthenia gravis (including
exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune
neuropathy.
- Ocular: Uveitis, iritis, and other ocular inflammatory
toxicities can occur. Some cases can be associated with retinal
detachment. Various grades of visual impairment to include
blindness can occur. If uveitis occurs in combination with other
immune-mediated adverse reactions, consider a
Vogt-Koyanagi-Harada-like syndrome, as this may require treatment
with systemic steroids to reduce the risk of permanent vision
loss.
- Gastrointestinal: Pancreatitis including increases in
serum amylase and lipase levels, gastritis, duodenitis.
- Musculoskeletal and connective tissue disorders:
Myositis/polymyositis, rhabdomyolysis and associated sequelae
including renal failure, arthritis, polymyalgia rheumatic.
- Endocrine: Hypoparathyroidism
- Other (hematologic/immune): Hemolytic anemia, aplastic
anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory
response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi
lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ
transplant rejection.
Infusion-Related Reactions IMFINZI can cause severe or
life-threatening infusion-related reactions. Monitor for signs and
symptoms of infusion-related reactions. Interrupt, slow the rate
of, or permanently discontinue IMFINZI based on the severity. See
Dosing and Administration for specific details. For Grade 1 or 2
infusion-related reactions, consider using pre-medications with
subsequent doses. Infusion-related reactions occurred in 2.2%
(42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%)
adverse reactions.
Complications of Allogeneic HSCT after IMFINZI Fatal and
other serious complications can occur in patients who receive
allogeneic hematopoietic stem cell transplantation (HSCT) before or
after being treated with a PD-1/L-1 blocking antibody.
Transplant-related complications include hyperacute
graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic
veno-occlusive disease (VOD) after reduced intensity conditioning,
and steroid-requiring febrile syndrome (without an identified
infectious cause). These complications may occur despite
intervening therapy between PD-1/L-1 blockade and allogeneic HSCT.
Follow patients closely for evidence of transplant-related
complications and intervene promptly. Consider the benefit versus
risks of treatment with a PD-1/L-1 blocking antibody prior to or
after an allogeneic HSCT.
Embryo-Fetal Toxicity Based on its mechanism of action
and data from animal studies, IMFINZI can cause fetal harm when
administered to a pregnant woman. Advise pregnant women of the
potential risk to a fetus. Advise females of reproductive potential
to use effective contraception during treatment with IMFINZI and
for at least 3 months after the last dose of IMFINZI.
Lactation There is no information regarding the presence
of IMFINZI in human milk; however, because of the potential for
adverse reactions in breastfed infants from IMFINZI, advise women
not to breastfeed during treatment and for at least 3 months after
the last dose.
Adverse Reactions
- In patients with UC in Study 1108 (n=182), the most common
adverse reactions (≥15%) were fatigue (39%), musculoskeletal pain
(24%), constipation (21%), decreased appetite (19%), nausea (16%),
peripheral edema (15%), and urinary tract infection (15%). The most
common Grade 3 or 4 adverse reactions (≥3%) were fatigue, urinary
tract infection, musculoskeletal pain, abdominal pain, dehydration,
and general physical health deterioration
- In patients with UC in Study 1108, discontinuation due to
adverse reactions occurred in 3.3% of patients. Serious adverse
reactions occurred in 46% of patients. The most frequent serious
adverse reactions (>2%) were acute kidney injury (4.9%), urinary
tract infection (4.4%), musculoskeletal pain (4.4%), liver injury
(3.3%), general physical health deterioration (3.3%), sepsis,
abdominal pain, and pyrexia/tumor associated fever (2.7% each)
- In patients with Stage III NSCLC in the PACIFIC study receiving
IMFINZI (n=475), the most common adverse reactions (≥20%) were
cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis
(34%), upper respiratory tract infections (26%), dyspnea (25%), and
rash (23%). The most common Grade 3 or 4 adverse reactions (≥3%)
were pneumonitis/radiation pneumonitis (3.4%) and pneumonia
(7%)
- In patients with Stage III NSCLC in the PACIFIC study receiving
IMFINZI (n=475), discontinuation due to adverse reactions occurred
in 15% of patients in the IMFINZI arm. Serious adverse reactions
occurred in 29% of patients receiving IMFINZI. The most frequent
serious adverse reactions (≥2%) were pneumonitis or radiation
pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation
pneumonitis and fatal pneumonia occurred in <2% of patients and
were similar across arms
- In patients with extensive-stage SCLC in the CASPIAN study
receiving IMFINZI plus chemotherapy (n=265), the most common
adverse reactions (≥20%) were nausea, fatigue/asthenia, and
alopecia. The most common Grade 3 or 4 adverse reaction (≥3%) was
fatigue/asthenia (3.4%)
- In patients with extensive-stage SCLC in the CASPIAN study
receiving IMFINZI plus chemotherapy (n=265), IMFINZI was
discontinued due to adverse reactions in 7% of the patients
receiving IMFINZI plus chemotherapy. Serious adverse reactions
occurred in 31% of patients receiving IMFINZI plus chemotherapy.
The most frequent serious adverse reactions reported in at least 1%
of patients were febrile neutropenia (4.5%), pneumonia (2.3%),
anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD
(1.1%). Fatal adverse reactions occurred in 4.9% of patients
receiving IMFINZI plus chemotherapy
The safety and effectiveness of IMFINZI have not been
established in pediatric patients.
Indications: IMFINZI is indicated for the treatment of
adult patients with locally advanced or metastatic urothelial
carcinoma who:
- Have disease progression during or following
platinum-containing chemotherapy.
- Have disease progression within 12 months of neoadjuvant or
adjuvant treatment with platinum-containing chemotherapy.
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 confirmatory trials.
IMFINZI is indicated for the treatment of adult patients with
unresectable Stage III non-small cell lung cancer (NSCLC) whose
disease has not progressed following concurrent platinum-based
chemotherapy and radiation therapy.
IMFINZI, in combination with etoposide and either carboplatin or
cisplatin, is indicated for the first-line treatment of adult
patients with extensive-stage small cell lung cancer (ES-SCLC).
Please see complete Prescribing Information, including
Patient Information.
NOTES TO EDITORS
About Stage III NSCLC Stage III NSCLC (locally advanced)
is commonly divided into three sub-categories (IIIA, IIIB and
IIIC), defined by how much the cancer has spread locally and the
possibility of surgery.1 Stage III disease is different from Stage
IV disease, where the cancer has spread (metastasized), as the
majority of Stage III patients are currently treated with curative
intent.1,2
Stage III NSCLC represents approximately one third of NSCLC
incidence and in 2015 was estimated to affect nearly 200,000
patients in the following eight large countries: China, France,
Germany, Italy, Japan, Spain, UK, and the US, with approximately
43,000 cases in the US alone.3,4 The majority of Stage III NSCLC
patients are diagnosed with unresectable tumors.5 Prior to approval
of IMFINZI in this setting, no new treatments beyond CRT had been
available to patients for decades.6-8
About Small cell lung cancer SCLC is a highly aggressive,
fast-growing form of lung cancer that typically recurs and
progresses rapidly, despite initial response to chemotherapy.9,10
About two thirds of SCLC patients are diagnosed with
extensive-stage disease, in which the cancer has spread widely
through the lung or to other parts of the body.11 Prognosis is
particularly poor, as only 6% of all SCLC patients will be alive
five years after diagnosis.11
About Bladder cancer This year, an estimated 81,400
adults in the United States will be diagnosed with bladder
cancer.12 Locally advanced and metastatic bladder cancer remains an
area of unmet medical need and typically only one in seven patients
is alive five years after diagnosis.13 Urothelial cancer (UC) is
the most common form of bladder cancer.14 Urothelial cancer (UC) is
the most common form of bladder cancer. 9 Bladder cancer is
projected to cause an estimated 17,980 cancer deaths in the US this
year.12,15 PD-L1 is widely expressed in tumor and immune cells in
patients with bladder cancer and helps tumors evade detection from
the immune system.16
About IMFINZI® (durvalumab) IMFINZI is a human monoclonal
antibody that binds to PD-L1 and blocks the interaction of PD-L1
with PD-1 and CD80, countering the tumor's immune-evading tactics
and releasing the inhibition of immune responses.
As part of a broad development program, IMFINZI is also being
tested as a monotherapy and in combinations including with
tremelimumab, an anti-CTLA4 monoclonal antibody and potential new
medicine, as a treatment for patients with NSCLC, SCLC, bladder
cancer, head and neck cancer, liver cancer, biliary tract cancer,
esophageal cancer, gastric cancer, cervical cancer, ovarian cancer,
endometrial cancer and other solid tumors.
About AstraZeneca Support Programs AstraZeneca strives to
ensure that appropriate patients and their oncologists have access
to IMFINZI and relevant support resources. These include
educational resources, an Oncology Nurse Educator program and
affordability and reimbursement programs, such as Access 360™.
Additionally, AstraZeneca has launched Lighthouse, a program
that provides support to patients during any immune-mediated
adverse events they may encounter during treatment, through
medically trained Lighthouse Advocates. The program aims to make
patients’ treatment experience as comfortable as possible. Find out
more about Lighthouse at LighthouseProgram.com or call
1-855-LHOUSE1 (1-855-546-8731).
About AstraZeneca in lung cancer AstraZeneca has a
comprehensive portfolio of approved and potential new medicines in
late-stage development for the treatment of different forms of lung
cancer spanning different histologies, several stages of disease,
lines of therapy and modes of action.
An extensive Immuno-Oncology (IO) development program focuses on
lung cancer patients without a targetable genetic mutation, which
represent up to three-quarters of all patients with lung cancer.17
IMFINZI, an anti-PDL1 antibody, is in development for patients with
advanced disease (POSEIDON and PEARL Phase III trials) and for
patients in earlier stages of disease, including
potentially-curative settings (MERMAID-1, AEGEAN, ADJUVANT BR.31,
PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC Phase III trials)
both as monotherapy and in combination with tremelimumab and/or
chemotherapy.
IMFINZI is also in development in the Phase II trials NeoCOAST,
COAST and HUDSON in combination with potential new medicines from
the early-stage pipeline, including Enhertu (trastuzumab
deruxtecan).
About AstraZeneca’s approach to IO IO is a therapeutic
approach designed to stimulate the body’s immune system to attack
tumors. The Company’s IO portfolio is anchored by immunotherapies
that have been designed to overcome anti-tumor immune suppression.
AstraZeneca is invested in using IO approaches that deliver
long-term survival for new groups of patients across tumor
types.
The Company is pursuing a comprehensive clinical-trial program
that includes IMFINZI as a monotherapy and in combination with
tremelimumab in multiple tumor types, stages of disease, and lines
of therapy, and where relevant using the PD-L1 biomarker as a
decision-making tool to define the best potential treatment path
for a patient. In addition, the ability to combine the IO portfolio
with radiation, chemotherapy, small targeted molecules from across
AstraZeneca’s Oncology pipeline, and from research partners, may
provide new treatment options across a broad range of tumors.
About AstraZeneca in oncology AstraZeneca has a
deep-rooted heritage in oncology and offers a quickly growing
portfolio of new medicines that has the potential to transform
patients' lives and the Company's future. With seven new medicines
launched between 2014 and 2020, and a broad pipeline of small
molecules and biologics in development, the Company is committed to
advance oncology as a key growth driver for AstraZeneca focused on
lung, ovarian, breast and blood cancers.
By harnessing the power of six scientific platforms –
Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response,
Antibody Drug Conjugates, Epigenetics, and Cell Therapies – and by
championing the development of personalized combinations,
AstraZeneca has the vision to redefine cancer treatment and one day
eliminate cancer as a cause of death.
About AstraZeneca AstraZeneca is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialization of prescription medicines,
primarily for the treatment of diseases in three therapy areas -
Oncology, Cardiovascular, Renal & Metabolism and Respiratory.
AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. For more
information, please visit www.astrazeneca-us.com and follow us on
Twitter @AstraZenecaUS.
References 1. ASCO. Cancer.net. Lung Cancer – Non-Small
Cell. Available at:
https://www.cancer.net/cancer-types/lung-cancer/view-all. Accessed
September 2020. 2. Cheema PK, et al. Perspectives on Treatment
Advances For Stage III Locally Advanced Unresectable Non-Small-Cell
Lung Cancer. Curr Oncol. 2019;26(1):37-42. 3. Antonia SJ, et al.
PACIFIC Investigators. Durvalumab After Chemoradiotherapy In Stage
III Non-Small-Cell Lung Cancer. N Engl J Med.
2017;377(20):1919-1929. 4. EpiCast Report: NSCLC Epidemiology
Forecast to 2025. GlobalData. 2016. 5. Provencio M, et al.
Inoperable Stage III Non-Small Cell Lung Cancer: Current Treatment
And Role Of Vinorelbine. J Thorac Dis. 2011;3:197-204. 6. Curran
WJ, et al. Sequential vs Concurrent Chemoradiation for Stage III
Non–Small Cell Lung Cancer: Randomized Phase III Trial RTOG 9410. J
Natl Cancer Inst. 2011;103(19):1452-1460. 7. NCCN. NCCN Clinical
Practice Guidelines in Oncology (NCCN Guidelines) - Non-Small Cell
Lung Cancer. Version 8. 2017.
https://www.nccn.org/professionals/physician_gls/pdf/nscl_blocks.pdf.
Accessed September 2020. 8. Hanna N, et al. Current Standards and
Clinical Trials in Systemic Therapy for Stage III Lung Cancer: What
is New? Am Soc Clin Oncol Educ Book. 2015:e442-447. 9. Kalemkerian
GP, et al. Treatment Options for Relapsed Small-Cell Lung Cancer:
What Progress Have We Made? J Oncol Pract. 2018;14(6):369-370. 10.
National Cancer Institute. NCI Dictionary – Small Cell Lung Cancer.
Available at
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-cell-lung-cancer.
Accessed November 2020. 11. Cancer.Net. Lung Cancer - Small Cell.
Available at
https://www.cancer.net/cancer-types/lung-cancer-small-cell.
Accessed November 2020. 12. ASCO. Cancer.net. Bladder Cancer.
Available at:
https://www.cancer.net/cancer-types/bladder-cancer/statistics.
Accessed August 2020. 13. Von der Maase H, et al. Long-Term
Survival Results of a Randomized Trial Comparing Gemcitabine Plus
Cisplatin, with Methotrexate, Vinblastine, Doxorubicin, Plus
Cisplatin in Patients with Bladder Cancer. J Clin Oncol.
2005;23:4602-4608. 14. American Society of Clinical Oncology.
Bladder Cancer: Introduction. Available at
https://www.cancer.net/cancer-types/bladder-cancer/introduction.
Accessed September 2020. 15. American Society of Clinical Oncology.
Bladder Cancer: Introduction. Available at
https://www.cancer.net/cancer-types/bladder-cancer/introduction.
Accessed August 2020. 16. Magdalene J, et al. Immune Responses in
Bladder Cancer-Role of Immune Cell Populations, Prognostic Factors
and Therapeutic Implications. Front Oncol. 2019;9:1270. 17.
Pakkala, S, et al. Personalized Therapy for Lung Cancer: Striking a
Moving Target. JCI Insight. 2018;3(15):e120858.
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