<p class="first" id="d8814673e544">This secondary analysis of the phase 1 CA209-003
clinical trial assesses the 5-year
survival and other related factors among patients with advanced melanoma, renal cell
carcinoma, or non–small cell lung cancer receiving nivolumab.
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<h5 class="section-title" id="d8814673e550">Question</h5>
<p id="d8814673e552">What is the 5-year survival, and what factors are associated
with 5-year survival
among patients with advanced melanoma, renal cell carcinoma, or non–small cell lung
cancer receiving nivolumab?
</p>
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<h5 class="section-title" id="d8814673e555">Findings</h5>
<p id="d8814673e557">In this secondary analysis of 270 patients from the CA209-003
clinical trial with
advanced melanoma, renal cell carcinoma, or non–small cell lung cancer, 5-year survival
was negatively associated with presence of bone or liver metastases and positively
associated with Eastern Cooperative Oncology Group performance status of 0, objective
response, degree of tumor burden reduction, and adverse event occurrence.
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<h5 class="section-title" id="d8814673e560">Meaning</h5>
<p id="d8814673e562">Nivolumab treatment may be associated with durable survival among
some heavily pretreated
patients with advanced melanoma, renal cell carcinoma, or non–small cell lung cancer;
characterizing factors associated with long-term survival may guide future anti–programmed
cell death 1–based clinical trial design.
</p>
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<h5 class="section-title" id="d8814673e566">Importance</h5>
<p id="d8814673e568">Nivolumab, a monoclonal antibody that inhibits programmed cell
death 1, is approved
by the US Food and Drug Administration for treating advanced melanoma, renal cell
carcinoma (RCC), non–small cell lung cancer (NSCLC), and other malignancies. Data
on long-term survival among patients receiving nivolumab are limited.
</p>
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<h5 class="section-title" id="d8814673e571">Objectives</h5>
<p id="d8814673e573">To analyze long-term overall survival (OS) among patients receiving
nivolumab and
identify clinical and laboratory measures associated with tumor regression and OS.
</p>
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<h5 class="section-title" id="d8814673e576">Design, Setting, and Participants</h5>
<p id="d8814673e578">This was a secondary analysis of the phase 1 CA209-003 trial
(with expansion cohorts),
which was conducted at 13 US medical centers and included 270 patients with advanced
melanoma, RCC, or NSCLC who received nivolumab and were enrolled between October 30,
2008, and December 28, 2011. The analyses were either specified in the original protocol
or included in subsequent protocol amendments that were implemented between 2008 and
2012. Statistical analysis was performed from October 30, 2008, to November 11, 2016.
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<h5 class="section-title" id="d8814673e581">Intervention</h5>
<p id="d8814673e583">In the CA209-003 trial, patients received nivolumab (0.1-10.0
mg/kg) every 2 weeks
in 8-week cycles for up to 96 weeks, unless they developed progressive disease, achieved
a complete response, experienced unacceptable toxic effects, or withdrew consent.
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<h5 class="section-title" id="d8814673e586">Main Outcomes and Measures</h5>
<p id="d8814673e588">Safety and activity of nivolumab; OS was a post hoc end point
with a minimum follow-up
of 58.3 months.
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<h5 class="section-title" id="d8814673e591">Results</h5>
<p id="d8814673e593">Of 270 patients included in this analysis, 107 (39.6%) had melanoma
(72 [67.3%] male;
median age, 61 [range, 29-85] years), 34 (12.6%) had RCC (26 [76.5%] male; median
age, 58 [range, 35-74] years), and 129 (47.8%) had NSCLC (79 [61.2%] male; median
age, 65 [range, 38-85] years). Overall survival curves showed estimated 5-year rates
of 34.2% among patients with melanoma, 27.7% among patients with RCC, and 15.6% among
patients with NSCLC. In a multivariable analysis, the presence of liver (odds ratio
[OR], 0.31; 95% CI, 0.12-0.83;
<i>P</i> = .02) or bone metastases (OR, 0.31; 95% CI, 0.10-0.93;
<i>P</i> = .04) was independently associated with reduced likelihood of survival at
5 years,
whereas an Eastern Cooperative Oncology Group performance status of 0 (OR, 2.74; 95%
CI, 1.43-5.27;
<i>P</i> = .003) was independently associated with an increased likelihood of 5-year
survival.
Overall survival was significantly longer among patients with treatment-related AEs
of any grade (median, 19.8 months; 95% CI, 13.8-26.9 months) or grade 3 or more (median,
20.3 months; 95% CI, 12.5-44.9 months) compared with those without treatment-related
AEs (median, 5.8 months; 95% CI, 4.6-7.8 months) (
<i>P</i> < .001 for both comparisons based on hazard ratios).
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<h5 class="section-title" id="d8814673e608">Conclusions and Relevance</h5>
<p id="d8814673e610">Nivolumab treatment was associated with long-term survival in
a subset of heavily
pretreated patients with advanced melanoma, RCC, or NSCLC. Characterizing factors
associated with long-term survival may inform treatment approaches and strategies
for future clinical trial development.
</p>
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<h5 class="section-title" id="d8814673e613">Trial Registration</h5>
<p id="d8814673e615">ClinicalTrials.gov identifier:
<a data-untrusted="" href="https://clinicaltrials.gov/ct2/show/NCT00730639" id="d8814673e617"
target="xrefwindow">NCT00730639</a>
</p>
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