Durable survival with nivolumab in patients with advanced RCC, NSCLC
medwireNews: Five-year data from the phase I CA209-003 trial indicate that the PD-1 inhibitor nivolumab is associated with long-term survival benefits among heavily pretreated patients with advanced renal cell carcinoma (RCC) or non-small-cell lung cancer (NSCLC).
With a minimum follow-up of 63.9 months, patients with RCC (n=34) had a median overall survival (OS) of 22.4 months and estimated 3- and 5-year OS rates of 40.1% and 27.7%, respectively. Corresponding figures for NSCLC patients (n=129), with a 58.3-month follow-up, were 9.9 months, 18.4% and 15.6%.
These estimated 5-year survival rates “exceed survival rates expected from conventional second-line or third-line therapies available for patients at the time that this trial was conducted,” write researcher Suzanne Topalian (Johns Hopkins Bloomberg–Kimmel Institute for Cancer Immunotherapy, Baltimore, Maryland, USA) and colleagues in JAMA Oncology, who cite an expected 5-year OS rate of around 6% for patients with stage IV NSCLC in 2008.
Multivariable analysis including 107 patients with advanced melanoma, in addition to those with RCC and NSCLC, found significant associations between baseline liver or bone metastases and a decreased likelihood of survival at 5 years, with odds ratios of 0.31 for both factors. Conversely, an ECOG performance status of 0 versus 1 or more was associated with an increased chance of 5-year survival, with an odds ratio of 2.74.
The researchers also found a significant association between the objective response rate and 5-year survival, with 74.5% of 55 patients alive at 5 years experiencing an objective response, compared with 11.6% of the 215 patients who had died within 5 years, giving an odds ratio of 22.3.
In addition, OS was significantly longer among patients experiencing treatment-related adverse events (AEs) of any grade, with a median OS of 19.8 months for those with any-grade AEs and 20.3 months for those with grade 3 or worse AEs, compared with 5.8 months for patients with no AEs. Similar results were seen when looking at potentially immune-mediated AEs, with median OS of 31.6, 39.6, and 8.2 months, respectively. “[These findings] highlight the possibility that anti-PD-1-mediated tumor regression and toxic effects are functionally associated,” say the researchers.
Finally, patients who were alive after 5 years had a significantly higher mean baseline absolute lymphocyte count and number of circulating regulatory T cells than those who did not survive.
“[These findings provide] preliminary evidence for early surrogate markers of long-term clinical benefit,” say Topalian and colleagues. “Such markers may be valuable on a per-patient basis and in designing the conduct and assessment of future trials of anti-PD-1 drugs.”
By Catherine Booth
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