By Dr Deepu
Patients with previously treated advanced or metastatic squamous
non-small cell lung cancer (NSCLC) had improved survival with an
immunotherapeutic drug than with chemotherapy, according to updated results
from a randomized trial.
Twice as many patients treated with nivolumab (Opdivo) remained
alive at 18 months as compared with those treated with docetaxel, and six times
as many patients were alive without progression at 18 months with nivolumab as
compared with the chemotherapy standard for NSCLC.
A second trial involving patients with treatment-refractory
squamous NSCLC similar improvement in outcomes with nivolumab versus docetaxel.
Accounting for about 20% of NSCLC cases, patients with
squamous-cell NSCLC represent a poor-prognosis minority who have few options
after progression or failure of first-line platinum-based chemotherapy.
Second-line docetaxel is associated with modest clinical activity (median
overall survival of 5 to 8 months, objective response rate of 3% to 9%) and significant
toxicity.
Nivolumab, a fully human PD-1 immune checkpoint inhibitor
antibody, has demonstrated activity in both squamous and nonsquamous NSCLC and
received FDA approval earlier this year for patients with squamous NSCLC that
had progressed during or after platinum-based chemotherapy.
At the American Society of
Clinical Oncology meeting
in June, investigators reported preliminary results from a randomized
comparison of nivolumab and docetaxel in patients with previously treated
advanced/metastatic squamous NSCLC. At that point the data showed a 1-year
survival of 42% with nivolumab versus 24% with docetaxel, and a median PFS of
9.2 vs 6.0 months, also in favor of nivolumab.
The anti-PD-1 antibody maintained superiority across all
prespecified subgroups, including age, geographic location, performance status,
and prior therapy. Moreover, the survival benefit persisted across all
categories of PD-L1 expression: positive, negative, and not quantifiable.
Patients treated with nivolumab had substantially fewer
treatment-related adverse events, including any adverse events (59% vs 87%),
grade 3-5 adverse events (8% vs 58%) and adverse events leading to
discontinuation (5% vs 10%). No treatment-related deaths occurred in the nivolumab
arm as compared with a 2% rate in the docetaxel group.
Similar superiority for nivolumab emerged from the phase II,
single-arm CheckMate 063trial,
which involved 117 patients with advanced/metastatic squamous NSCLC that had
progressed during or after platinum-based chemotherapy plus at least one other
systemic regimen.
The trial had a primary endpoint of independently reviewed and
confirmed objective response. The data showed an overall response rate of 15%
(17 of 117), three fourths of which are ongoing said Horn. The median time to
response was 3.3 months, and the median duration of response has yet to be
reached (range of 1.9 to 11.5 months). The cohort had a median PFS of 1.9
months and a 1-year PFS of 20%.
Responses were observed across all predefined subgroups,
including age, number of prior therapies, performance status, and level of
PD-L1 expression.
After a median follow-up of 8 months, the cohort had a median
overall survival of 8.1 months, a 1-year overall survival of 39%, and 18-month
survival of 27%. The updated data remained consistent with the primary analysis
in July 2014, which showed a median overall survival of 8.2 months and 1-year
overall survival of 41%.
Overall, 17% of the patients had grade 3/4 adverse events, the
most common being gastrointestinal and pulmonary in nature (3% each). Horn
noted that no new grade 3/4 adverse events occurred from the initial assessment
through the updated analysis in June 2015.
