Predictors of long-term survival of patients with advanced melanoma, renal cell carcinoma (RCC), non–small cell lung cancer (NSCLC), and other malignancies treated with nivolumab include the absence of liver or bone metastases, excellent baseline performance status, and the presence of grade 3 or greater treatment-related adverse events, investigators have found.
A secondary analysis of the phase 1with expansion cohorts showed that, among 270 heavily pretreated patients with melanoma, RCC, and NSCLC who received single-agent nivolumab (Opdivo) during this trial, those with liver or bone metastases had a 69% higher risk for death within 5 years.
In contrast, patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 had a nearly threefold higher chance for survival, compared with patients with less favorable performance status scores, reported Suzanne L. Topalian, MD, from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore and colleagues.
“The results of this study suggest that survival benefits reported in the more limited follow-up of recent nivolumab randomized clinical trials may persist for prolonged periods in some patients, extending to at least 5 years,” they wrote in.
In the CA209-003 trial, investigators enrolled patients 18 years or older with documented evidence of advanced melanoma, RCC, NSCLC, castration-resistant prostate cancer, or colorectal cancer. To be eligible, patients needed to have received 1-5 previous systemic therapies for advanced or recurrent cancer, measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and an ECOG performance status of 0-2. The current survival analysis included data on 107 patients with melanoma, 34 with RCC, and 129 with NSCLC.
Estimated 5-year overall survival rates were 34.2% for patients with melanoma, 27.7% for patients with RCC, and 15.6% for patients with NSCLC. A multivariable analysis controlling for age, sex, performance status, metastatic disease, and number of prior therapies showed that the presence of either liver or bone metastases was associated with an odds ratio for 5-year survival of 0.31 (P = .02 and .04, respectively).
One factor favorably associated with survival included ECOG performance status 0 (OR, 2.74; P = .003). The investigators also found that treatment-related adverse events (AEs) were associated with longer overall survival, with a median of 19.8 months for patients with any grade of treatment-related event and 20.3 months for patients with grade 3 or greater events, compared with a median of 5.8 months for patients with no treatment-related events (P less than .001 for each comparison based on hazard ratios).
“Of note, patients in our study who developed treatment-related AEs, regardless of whether the AEs were deemed to have an immune-mediated causality, had significantly higher ORRs [overall response rates] and prolonged 5-year OS. These findings are reminiscent of some reports of anti–CTLA-4 therapy and align with other studies of anti–PD-1 therapies, “ Dr. Topalian and associates wrote.
The study and the secondary analysis were supported by Bristol-Myers Squibb. Dr. Topalian disclosed grants and travel reimbursements from Bristol-Myers Squibb and consulting fees with other entities. Multiple co-authors reported similar relationships. Four of the co-authors are Bristol-Myers Squibb employees.
SOURCE: Topalian SL et al. JAMA Oncology. 2019 Jul 25. .