Results of study conducted in Canada, Australia and Europe presented at Society for Melanoma
Research and published in The New England Journal of Medicine
show one-year survival rate of 73% in patients on Opdivo,
versus 42% on dacarbazine and a 58% decrease in the risk of death
(Hazard Ratio [HR] = 0.42, p<0.0001).
MONTREAL, Nov. 19,
2014 /CNW/ - Results of a Phase 3 randomized
double-blind study conducted in Canada, Australia and Europe show that Opdivo (nivolumab), an
investigational PD-1 immune checkpoint inhibitor from Bristol-Myers
Squibb Company, demonstrated superior overall survival compared to
the chemotherapy dacarbazine (DTIC) in patients with treatment
naïve BRAF wild-type advanced melanoma (n=418).
The study met the primary endpoint of overall
survival (OS). In patients treated with Opdivo, median
overall survival was not reached (since more than half of
patients survived the study period) and was 10.8 months for DTIC
(95% CI 9.3–12.1). The one-year survival rate for Opdivo
was 73% (95% CI = 66-79) vs. 42% (95% CI = 33-51) for DTIC and
there was a 58% decrease in the risk of death for patients treated
with Opdivo (Hazard Ratio for death [HR]:0.42, 99.79% CI =
0.25-0.73; P<0.0001). This survival advantage was observed in
Opdivo-treated patients, independently of PD-L1
expression.
The CheckMate-066 study was stopped early, in
June 2014, because an analysis
conducted by the independent Data Monitoring Committee showed
evidence of superior overall survival in patients receiving
Opdivo compared to DTIC. Results were published this week in
The New England Journal of Medicine and highlighted as a
late-breaking presentation during an oral session at the Society
for Melanoma Research 2014 International Congress in Zurich, Switzerland.
"The results from the CheckMate-066 study are
significant for two reasons," said Dr. David Hogg, one of the study investigators and
an oncologist and hematologist at Princess Margaret Hospital and
Director of the Melanoma Oncology Site Group at University Health
Network in Toronto. "First,
nivolumab was clearly superior in first line treatment of melanoma
to the chemotherapy control. This finding should change our
approach to melanoma treatment. And second, response to nivolumab
was seen in patients regardless of PD-L1 expression, meaning all
melanoma patients should benefit from the drug."
Safety was reported in all patients treated in
the Opdivo and DTIC arms. Fewer discontinuations were
observed with Opdivo than DTIC (6.8% vs. 11.7%) as well as
for treatment-related Grade 3/4 adverse events (AEs) (11.7% vs.
17.6%), which were managed using established safety algorithms. The
most common Opdivo treatment-related AEs were fatigue (20%),
pruritus (17%), and nausea (16.5%). Common adverse events in the
DTIC arm were consistent with those in previous reports and
included nausea (41.5%), vomiting (21%), fatigue (15%), diarrhea
(15%) and hematological toxicities. No deaths were attributed to
study drug toxicity in either arm.
About the Checkmate-066 Trial
Design
CheckMate-066 is a Phase 3 randomized, double-blind
study of patients with previously untreated BRAF wild-type
unresectable Stage III and IV melanoma. The trial enrolled 418
patients who were randomized to receive either Opdivo 3
mg/kg every two weeks (n=210) or DTIC 1000 mg/m2 every three weeks
(n=208). Treatment continued until there was disease progression on
an acceptable level of toxicity. Thirty-eight per cent of patients
in the DTIC arm received Yervoy (ipilimumab) after stopping
study treatment. All randomized patients were followed for up to
16.7 months at the time of database lock. The primary endpoint was
overall survival. Secondary endpoints included progression free
survival (PFS) and objective response rate (ORR) by RECIST v1.1
criteria and PD-L1 expression as a predictive biomarker of OS.
PD-L1 positivity was defined bas at least 5% of tumor cells showing
cell-surface PD-L1 staining.
Detailed Study Results
Median OS was
not reached for patients treated with Opdivo and was 10.8
months for DTIC (95% CI 9.3–12.1). The one-year survival rate was
73% for Opdivo (95% CI = 66-79) vs. 42% for DTIC (95% CI =
33-51). There was a 58% decrease in the risk of death for patients
treated with Opdivo (Hazard Ratio for death [HR]: 0.42;
99.79% CI = 0.25-0.73; P<0.0001). Median PFS was 5.1 months (95%
CI, 3.5 to 10.8) and 2.2 months (95% CI, 2.1 to 2.4), respectively
(HR: 0.43; 95% CI = 0.34–0.56; P < 0.0001).
ORR was also significantly higher for
Opdivo than DTIC (40% vs. 14%, p<0.0001). Complete
responses were observed in 7.6% of Opdivo-treated patients
vs. 1% for DTIC. Median duration of response was not reached for
Opdivo responders and was six months for DTIC (95% CI,
3.0–not estimable). Responses were ongoing in 86% of Opdivo
responders compared to 51% for DTIC responders.
In both the PD-L1 positive and PD-L1
negative/indeterminate subgroups, Opdivo-treated patients
had improved OS vs. DTIC (unstratified HR 0.30, 95% CI, 0.15-0.60
in PD-L1 positive patients; 0.48, 95% CI 0.32-0.71 in PD-L1
negative/indeterminate patients). Median OS was not reached in
either PD-L1 subgroup in the Opdivo arm. In the DTIC arm,
mOS was slightly longer in the PD-L1 positive subgroup (12 vs. 10
months).
About Opdivo
Cancer cells may
exploit "regulatory" pathways, such as checkpoint pathways, to hide
from the immune system and shield the tumor from immune attack.
Opdivo is an investigational, fully-human PD-1 immune
checkpoint inhibitor that binds to the checkpoint receptor PD-1
(programmed death-1) expressed on activated T-cells.
Bristol-Myers
Squibb has a broad, global development program to study
Opdivo in multiple tumour types consisting of more than 35
trials – as monotherapy or in combination with other therapies – in
which more than 7,000 patients have been enrolled worldwide. Among
these are several potentially registrational trials in non-small
cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC),
head and neck cancer, glioblastoma and non-Hodgkin lymphoma.
About Advanced Melanoma
Melanoma is a
form of skin cancer characterized by the uncontrolled growth of
pigment-producing cells (melanocytes) located in the skin.
Metastatic melanoma is the deadliest form of the disease, and
occurs when cancer spreads beyond the surface of the skin to the
other organs, such as the lymph nodes, lungs, brain or other areas
of the body. The incidence of melanoma has been increasing for at
least 30 years. In 2012, an estimated 232,130 melanoma cases were
diagnosed globally. Melanoma is mostly curable when treated in its
early stages. However, in its late stages, the average survival
rate has historically been just six months with a one-year
mortality rate of 75 per cent, making it one of the most aggressive
forms of cancer.
Immuno-Oncology at Bristol-Myers
Squibb
Surgery, radiation, cytotoxic or targeted therapies
have represented the mainstay of cancer treatment over the last
several decades, but long-term survival and a positive quality of
life have remained elusive for many patients with advanced
disease.
To address this unmet medical need, Bristol-Myers
Squibb is leading advances in the innovative field of
immuno-oncology, which involves agents whose primary mechanism is
to work directly with the body's immune system to fight cancer. The
company is exploring a variety of compounds and immunotherapeutic
approaches for patients with different types of cancer, including
researching the potential of combining immuno-oncology agents that
target different and complementary pathways in the treatment of
cancer.
Bristol-Myers
Squibb is committed to advancing the science of
immuno-oncology, with the goal of changing survival expectations
and the way patients live with cancer.
About Bristol-Myers Squibb
Canada
Bristol-Myers Squibb
Canada is an indirect wholly-owned subsidiary of
Bristol-Myers Squibb Company, a global biopharmaceutical company
whose mission is to discover, develop and deliver innovative
medicines that help patients prevail over serious diseases. For
more information, please visit www.bmscanada.ca.
SOURCE Bristol-Myers Squibb Canada