Bristol-Myers Squibb Announces Long-Term Survival Results from Pooled Analyses of Opdivo (nivolumab) in Previously-Treated Non-Small Cell Lung Cancer Patients
April 2, 2019Analyses include the longest follow-up of lung cancer patients
treated with Immuno-Oncology therapy in phase 3 randomized trials
PRINCETON, N.J.–(BUSINESS WIRE)—Bristol-Myers
Squibb Company (NYSE: BMY) today announced results from pooled
analyses of survival data from four studies (CheckMate -017, -057, -063
and -003; n=664) in patients with previously-treated advanced non-small
cell lung cancer (NSCLC) who were treated with Opdivo
(nivolumab). In the pooled analysis of the four studies, 14% of all Opdivo-treated
patients were alive at four years. Notably, in patients with PD-L1 ≥1%
and <1%, four-year overall survival (OS) rates were 19% and 11%,
respectively.
In the pooled analysis of the two phase 3 trials, CheckMate -017 and
-057, the four-year OS rate for Opdivo-treated patients was 14%
compared to 5% for docetaxel-treated patients. Additionally, exploratory
landmark analysis of OS found that of patients who had a complete or
partial response at six months, 58% of those treated with Opdivo
were alive four years later vs. 12% of patients treated with docetaxel.
Of patients who had stable disease at six months, 19% of those treated
with Opdivo were alive four years later vs. 2% of patients
treated with docetaxel. The data were presented today (Abstract CT195)
at the American Association for Cancer Research (AACR) Annual Meeting
2019 in Atlanta.
Long-term safety data for Opdivo from all four studies were
consistent with the known adverse event profile and did not reveal any
new safety signals. The discontinuation rate due to treatment-related
adverse events (AEs) was 8.7% in patients treated with Opdivo.
The most common treatment-related AE was fatigue (in 21.7% of patients).
Scott Antonia, M.D., Ph.D., director of the Duke Cancer Institute Center
for Cancer Immunotherapy, commented, “These analyses in a large
population of patients with previously-treated advanced non-small cell
lung cancer show, for the first time, that response to Opdivo
correlates to a survival benefit over many years. These long-term
survival outcomes are particularly interesting given that, historically,
the average five-year survival rate for this patient population is
approximately 5%.”
Sabine Maier, M.D., development lead, thoracic cancers, Bristol-Myers
Squibb, said, “The positive survival curve observed in these pooled
analyses offers a more holistic view of long-term survival outcomes than
what we’ve seen in the individual studies and provides new insights into
the value Opdivo can provide for lung cancer patients in the
second-line setting. These data also serve to reinforce our longstanding
commitment to delivering cancer therapies that may offer more durable
responses for patients in critical need.”
About the Analyses
These pooled analyses were conducted to evaluate the long-term benefit
(with a minimum follow-up of four years) of Opdivo and impact of
response or disease control on subsequent long-term overall survival
(OS). The pooled analysis of CheckMate -017 and CheckMate -057
represents the longest follow-up from phase 3 randomized trials of
previously treated advanced non-small cell lung cancer (NSCLC) patients
treated with Immuno-Oncology therapy.
OS was estimated for patients with NSCLC across histologies treated with Opdivo
in pooled analyses from CheckMate -017, -057, -063, and -003 (n=664),
and for patients randomized to Opdivo (n=427) or docetaxel
(n=427) in pooled analyses from CheckMate -017 and -057. Other analyses
of CheckMate -017 and -057 included estimation of OS in patients alive
at six months by response status at six months, and OS in all responders
(complete or partial response) from the time of response.
About Lung Cancer
Lung cancer is the leading cause of cancer deaths globally. The two main
types of lung cancer are non-small cell and small cell. Non-small cell
lung cancer (NSCLC) is one of the most common types of lung cancer and
accounts for up to 85% of diagnoses. Survival rates vary depending on
the stage and type of the cancer when diagnosed. For patients diagnosed
with metastatic lung cancer, the five-year survival rate is
approximately 5%.
Bristol-Myers Squibb: Advancing Oncology
Research
At Bristol-Myers Squibb, patients are at the center of everything we do.
The focus of our research is to increase quality, long-term survival for
patients with cancer and make cure a possibility. Through a unique
multidisciplinary approach powered by translational science, we harness
our deep scientific experience in oncology and Immuno-Oncology (I-O)
research, to identify novel treatments tailored to individual patient
needs. Our researchers are developing a diverse, purposefully built
pipeline designed to target different immune system pathways and address
the complex and specific interactions between the tumor, its
microenvironment and immune system. We source innovation internally and
in collaboration with academia, government, advocacy groups and
biotechnology companies, to help make the promise of transformational
medicines, like I-O, a reality for patients.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor
that is designed to uniquely harness the body’s own immune system to
help restore anti-tumor immune response. By harnessing the body’s own
immune system to fight cancer, Opdivo has become an
important treatment option across multiple cancers.
Opdivo’s leading global development program is based on
Bristol-Myers Squibb’s scientific expertise in the field of
Immuno-Oncology, and includes a broad range of clinical trials across
all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical
development program has enrolled more than 25,000 patients. The Opdivo trials
have contributed to gaining a deeper understanding of the potential role
of biomarkers in patient care, particularly regarding how patients may
benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint
inhibitor to receive regulatory approval anywhere in the world. Opdivo is
currently approved in more than 65 countries, including the United
States, the European Union, Japan and China. In October 2015, the
Company’s Opdivo and Yervoy combination regimen was the
first Immuno-Oncology combination to receive regulatory approval for the
treatment of metastatic melanoma and is currently approved in more than
50 countries, including the United States and the European Union.
U.S. FDA-APPROVED INDICATIONS FOR OPDIVO®
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 mutation-positive unresectable or
metastatic melanoma. This indication is approved under accelerated
approval based on progression-free survival. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 wild-type unresectable or
metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY®
(ipilimumab), is indicated for the treatment of patients with
unresectable or metastatic melanoma. This indication is approved under
accelerated approval based on progression-free survival. Continued
approval for this indication may be contingent upon verification and
description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of
patients with metastatic non-small cell lung cancer (NSCLC) with
progression on or after platinum-based chemotherapy. Patients with EGFR
or ALK genomic tumor aberrations should have disease progression on
FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO® (nivolumab) is indicated for the treatment of
patients with metastatic small cell lung cancer (SCLC) with progression
after platinum-based chemotherapy and at least one other line of
therapy. This indication is approved under accelerated approval based on
overall response rate and duration of response. Continued approval for
this indication may be contingent upon verification and description of
clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of
patients with advanced renal cell carcinoma (RCC) who have received
prior anti-angiogenic therapy.
OPDIVO® (nivolumab), in combination with YERVOY®
(ipilimumab), is indicated for the treatment of patients with
intermediate or poor risk, previously untreated advanced renal cell
carcinoma (RCC).
OPDIVO® (nivolumab) is indicated for the treatment of adult
patients with classical Hodgkin lymphoma (cHL) that has relapsed or
progressed after autologous hematopoietic stem cell transplantation
(HSCT) and brentuximab vedotin or after 3 or more lines of systemic
therapy that includes autologous HSCT. This indication is approved under
accelerated approval based on overall response rate. Continued approval
for this indication may be contingent upon verification and description
of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of
patients with recurrent or metastatic squamous cell carcinoma of the
head and neck (SCCHN) with disease progression on or after
platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of
patients with locally advanced or metastatic urothelial carcinoma who
have disease progression during or following platinum-containing
chemotherapy or 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.
OPDIVO® (nivolumab), as a single agent, is indicated for the
treatment of adult and pediatric (12 years and older) patients with
microsatellite instability-high (MSI-H) or mismatch repair deficient
(dMMR) metastatic colorectal cancer (CRC) that has progressed following
treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This
indication is approved under accelerated approval based on overall
response rate and duration of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY®
(ipilimumab), is indicated for the treatment of adults and pediatric
patients 12 years and older with microsatellite instability-high (MSI-H)
or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC)
that has progressed following treatment with a fluoropyrimidine,
oxaliplatin, and irinotecan. This indication is approved under
accelerated approval based on overall response rate and duration of
response. Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of
patients with hepatocellular carcinoma (HCC) who have been previously
treated with sorafenib. This indication is approved under accelerated
approval based on tumor response rate and durability of response.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in the confirmatory
trials.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment
of patients with melanoma with involvement of lymph nodes or metastatic
disease who have undergone complete resection.
IMPORTANT SAFETY INFORMATION
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY can result in severe and fatal immune-mediated adverse
reactions. These immune-mediated reactions may involve any organ system;
however, the most common severe immune-mediated adverse reactions are
enterocolitis, hepatitis, dermatitis (including toxic epidermal
necrolysis), neuropathy, and endocrinopathy. The majority of these
immune-mediated reactions initially manifested during treatment;
however, a minority occurred weeks to months after discontinuation of
YERVOY.
Assess patients for signs and symptoms of enterocolitis, dermatitis,
neuropathy, and endocrinopathy, and evaluate clinical chemistries
including liver function tests (LFTs), adrenocorticotropic hormone
(ACTH) level, and thyroid function tests, at baseline and before each
dose.
Permanently discontinue YERVOY and initiate systemic high-dose
corticosteroid therapy for severe immune-mediated reactions.
Immune-Mediated Pneumonitis
OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been
reported. Monitor patients for signs with radiographic imaging and for
symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more
severe pneumonitis. Permanently discontinue for Grade 3 or 4 and
withhold until resolution for Grade 2. In patients receiving OPDIVO
monotherapy, fatal cases of immune-mediated pneumonitis have occurred.
Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In
patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated
pneumonitis occurred in 6% (25/407) of patients. In RCC patients
receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated
pneumonitis occurred in 4.4% (24/547) of patients. In MSI-H/dMMR mCRC
patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated
pneumonitis occurred in 1.7% (2/119) of patients.
In Checkmate 205 and 039, pneumonitis, including interstitial lung
disease, occurred in 6.0% (16/266) of patients receiving OPDIVO.
Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients
receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=12).
Immune-Mediated Colitis
OPDIVO can cause immune-mediated colitis. Monitor patients for signs and
symptoms of colitis. Administer corticosteroids for Grade 2 (of more
than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for
Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent
colitis upon re-initiation of OPDIVO. When administered with YERVOY,
withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for
Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO
monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of
patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg,
immune-mediated colitis occurred in 26% (107/407) of patients including
three fatal cases. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY
1 mg/kg, immune-mediated colitis occurred in 10% (52/547) of patients.
In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1
mg/kg, immune-mediated colitis occurred in 7% (8/119) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening,
or fatal (diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal
signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%)
patients. Across all YERVOY-treated patients in that study (n=511), 5
(1%) developed intestinal perforation, 4 (0.8%) died as a result of
complications, and 26 (5%) were hospitalized for severe enterocolitis.
Immune-Mediated Hepatitis
OPDIVO can cause immune-mediated hepatitis. Monitor patients for
abnormal liver tests prior to and periodically during treatment.
Administer corticosteroids for Grade 2 or greater transaminase
elevations. For patients without HCC, withhold OPDIVO for Grade 2 and
permanently discontinue OPDIVO for Grade 3 or 4. For patients with HCC,
withhold OPDIVO and administer corticosteroids if AST/ALT is within
normal limits at baseline and increases to >3 and up to 5 times the
upper limit of normal (ULN), if AST/ALT is >1 and up to 3 times ULN at
baseline and increases to >5 and up to 10 times the ULN, and if AST/ALT
is >3 and up to 5 times ULN at baseline and increases to >8 and up to 10
times the ULN. Permanently discontinue OPDIVO and administer
corticosteroids if AST or ALT increases to >10 times the ULN or total
bilirubin increases >3 times the ULN. In patients receiving OPDIVO
monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of
patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg,
immune-mediated hepatitis occurred in 13% (51/407) of patients. In RCC
patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated
hepatitis occurred in 7% (38/547) of patients. In MSI-H/dMMR mCRC
patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated
hepatitis occurred in 8% (10/119) of patients.
In Checkmate 040, immune-mediated hepatitis requiring systemic
corticosteroids occurred in 5% (8/154) of patients receiving OPDIVO.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening,
or fatal hepatotoxicity (AST or ALT elevations >5x the ULN or total
bilirubin elevations >3x the ULN; Grade 3-5) occurred in 8 (2%) patients,
with fatal hepatic failure in 0.2% and hospitalization in 0.4%.
Immune-Mediated Neuropathies
In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal
Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor
neuropathy were reported.
Immune-Mediated Endocrinopathies
OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal
insufficiency, autoimmune thyroid disorders, and Type 1 diabetes
mellitus. Monitor patients for signs and symptoms of hypophysitis, signs
and symptoms of adrenal insufficiency, thyroid function prior to and
periodically during treatment, and hyperglycemia. Administer hormone
replacement as clinically indicated and corticosteroids for Grade 2 or
greater hypophysitis. Withhold for Grade 2 or 3 and permanently
discontinue for Grade 4 hypophysitis. Administer corticosteroids for
Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently
discontinue for Grade 3 or 4 adrenal insufficiency. Administer
hormone-replacement therapy for hypothyroidism. Initiate medical
management for control of hyperthyroidism. Withhold OPDIVO for Grade 3
and permanently discontinue for Grade 4 hyperglycemia.
In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6%
(12/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY
3 mg/kg, hypophysitis occurred in 9% (36/407) of patients. In RCC
patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, hypophysitis
occurred in 4.6% (25/547) of patients. In MSI-H/dMMR mCRC patients
receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated
hypophysitis occurred in 3.4% (4/119) of patients. In patients receiving
OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of
patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg,
adrenal insufficiency occurred in 5% (21/407) of patients. In RCC
patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, adrenal
insufficiency occurred in 7% (41/547) of patients. In MSI-H/dMMR mCRC
patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, adrenal
insufficiency occurred in 5.9% (7/119) of patients. In patients
receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in
hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism
occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In
patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, hypothyroidism or
thyroiditis resulting in hypothyroidism occurred in 22% (89/407) of
patients. Hyperthyroidism occurred in 8% (34/407) of patients receiving
this dose of OPDIVO with YERVOY. In RCC patients receiving OPDIVO 3
mg/kg with YERVOY 1 mg/kg, hypothyroidism or thyroiditis resulting in
hypothyroidism occurred in 22% (119/547) of patients. Hyperthyroidism
occurred in 12% (66/547) of patients receiving this dose of OPDIVO with
YERVOY. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY
1 mg/kg, hypothyroidism or thyroiditis resulting in hypothyroidism
occurred in 15% (18/119) of patients. Hyperthyroidism occurred in 12%
(14/119) of patients. In patients receiving OPDIVO monotherapy, diabetes
occurred in 0.9% (17/1994) of patients. In patients receiving OPDIVO 1
mg/kg with YERVOY 3 mg/kg, diabetes occurred in 1.5% (6/407) of
patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg,
diabetes occurred in 2.7% (15/547) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe to
life-threatening immune-mediated endocrinopathies (requiring
hospitalization, urgent medical intervention, or interfering with
activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients.
All 9 patients had hypopituitarism, and some had additional concomitant
endocrinopathies such as adrenal insufficiency, hypogonadism, and
hypothyroidism. Six of the 9 patients were hospitalized for severe
endocrinopathies.
Immune-Mediated Nephritis and Renal Dysfunction
OPDIVO can cause immune-mediated nephritis. Monitor patients for
elevated serum creatinine prior to and periodically during treatment.
Administer corticosteroids for Grades 2-4 increased serum creatinine.
Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4
increased serum creatinine. In patients receiving OPDIVO monotherapy,
immune-mediated nephritis and renal dysfunction occurred in 1.2%
(23/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY
3 mg/kg, immune-mediated nephritis and renal dysfunction occurred in
2.2% (9/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with
YERVOY 1 mg/kg, immune-mediated nephritis and renal dysfunction occurred
in 4.6% (25/547) of patients. In MSI-H/dMMR mCRC patients receiving
OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated nephritis and renal
dysfunction occurred in 1.7% (2/119) of patients.
Immune-Mediated Skin Adverse Reactions and Dermatitis
OPDIVO can cause immune-mediated rash, including Stevens-Johnson
syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with
fatal outcome. Administer corticosteroids for Grade 3 or 4 rash.
Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For
symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient
for specialized care for assessment and treatment; if confirmed,
permanently discontinue. In patients receiving OPDIVO monotherapy,
immune-mediated rash occurred in 9% (171/1994) of patients. In patients
receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated rash
occurred in 22.6% (92/407) of patients. In RCC patients receiving OPDIVO
3 mg/kg with YERVOY 1 mg/kg, immune-mediated rash occurred in 16.6%
(91/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3
mg/kg with YERVOY 1 mg/kg, immune-mediated rash occurred in 14% (17/119)
of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening,
or fatal immune-mediated dermatitis (eg, Stevens-Johnson syndrome, toxic
epidermal necrolysis, or rash complicated by full thickness dermal
ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade
3-5) occurred in 13 (2.5%) patients. 1 (0.2%) patient died as a result
of toxic epidermal necrolysis. 1 additional patient required
hospitalization for severe dermatitis.
Immune-Mediated Encephalitis
OPDIVO can cause immune-mediated encephalitis. Evaluation of patients
with neurologic symptoms may include, but not be limited to,
consultation with a neurologist, brain MRI, and lumbar puncture.
Contacts
Media:
Eric Van Zanten, 610-529-6219
[email protected]
Investors:
Bill
Szablewski, 609-252-5894
[email protected]
Tim
Power, 609-252-7509
[email protected]
