“We are at a fortunate time to have multiple routes to ‘lifetime’ (T-cell) memory (including ipilimumab [Yervoy] and nivolumab [Opdivo]),” said Jedd D. Wolchok, MD, PhD, of Memorial Sloan Kettering Cancer Center, New York, who was the formal discussant of the CA909-003 trial at the American Association for Cancer Research Annual Meeting.

The trial explored multiple dose levels of programmed cell death 1 (PD-1) blockade across solid tumors. The 3-mg/kg dose was associated with an overall response rate, which is consistent with other studies, Dr. Wolchok noted.

Durability of Response

“This shows us we can get valuable information from phase I studies. Seeing the durability of response is very important, especially in the context of maximal treatment time of 96 months,” he continued.

“A significant number of patients maintained their responses for 2 or 3 additional years after cessation of therapy. We are still grappling with how long to continue treatment with these immunotherapies.”

The finding that retreated patients can benefit contributes to the discussion of how long to treat patients. “The five retreated patients who achieved a response implies that there is no optimal duration of therapy and that you can observe and then restart therapy.”

In one of the five patients, immunotherapy enabled resection of an oligometastasis, which may be an important value of nivolumab beyond response rates, he added.

Unanswered Questions

Dr. Wolchok said that data from ongoing randomized trials will determine whether the combination of nivolumab plus ipilimumab or other immunotherapy combinations have improved survival outcomes compared with the 003 study of single-agent nivolumab.

Open questions remain how long to treat with the newer immunotherapies. “We need to know whether responding patients can stop therapy and then be restarted if progression occurs, or is persistent dosing necessary?” Dr. Wolchok commented.

Dr. Wolchok’s overall take-home message was that PD-1 blockade is yet another means to long-term disease control in melanoma. ■

Disclosure: Dr. Wolchok has been a consultant for, has received research support from, or has stock ownership in Bristol-Myers Squibb and Merck.