Tumors regressed at various sites, including, in one patient, an unresectable lesion that had eroded through the zygomatic arch into the orbit. Response occurred within 4 months of treatment initiation. This lesion remains in remission. A biopsy showed fibrosis and infiltrating lymphocytes, but no tumor cells. This finding hints that residual tumor seen in some patients’ imaging may in fact be scarring. If that is true, the researchers said, they could have underestimated the real response rate.
Seventeen of the 33 patients who responded discontinued treatment for reasons other than progression. Among these, 12 (71%) maintained their response for 16-56 weeks; in eight of these, response was ongoing at the time of data analysis. Among these is a patient who had metastatic lesions in the adrenal gland, small bowel, and mesenteric lymph nodes.
An additional 7% (7 patients) experienced stable disease for at least 24 weeks at doses of 0.1 to 10 mg/kg. "Unconventional" response patterns not meeting RECIST criteria occurred in four patients, but there was no associated dose pattern; three had received 1 mg/kg and the fourth, 10 mg/kg. Disease progressed in 11 patients treated at doses of 0.1 to 03 mg/kg; none of these responded to a dose escalation, the investigators said.
Nivolumab’s safety data were excellent when compared with other cancer treatments, they noted. Most adverse events occurred within the first 6 months – a hint that close observation and early intervention could minimize their impact. The most common were fatigue (32%), rash (23%), and diarrhea (18%). Grades 3 and 4 adverse events occurred in 24 patients. Treatment-related select adverse events of any grade occurred in 58 (54%). The most common were skin disorders (36%), gastrointestinal events (18%), and endocrinopathies (13%) – not unexpected in an immunomodulating drug. There were no drug-related deaths in the study.
Although this study examined nivolumab as monotherapy, others are looking at a possibly synergistic effect when it’s given with other immunomodulators, and with chemotherapy, kinase inhibitors, or cancer vaccines.
"Innovative, rational treatment combinations based on preclinical evidence may be needed to realize the full therapeutic potential of PD-1 blockade," the investigators said.
Dr. Topalian and several of her coauthors received research funding or had other financial relationships with Bristol-Myers Squibb, sponsor of the study.