Zosia Chustecka

June 02, 2014

CHICAGO — Today, the news coming out of the 2014 Annual Meeting of the American Society of Clinical Oncology® (ASCO) from late-breaking abstracts highlighted at the morning press briefing focuses on immunotherapies and the impact they are making on melanoma, as well as a novel approach to the treatment of cervical cancer. A summary follows below, but please check back later in the day for detailed reports with reactions to the news.

"The field of immunotherapy has exploded in the last decade, and more and more patients are benefiting," commented Steven O'Day, MD, clinical associate professor of medicine at the University of Southern California Keck School of Medicine in Los Angeles.

One of these "explosions" was the launch in 2011 of ipilimumab (Yervoy), the first immune-checkpoint inhibitor for use in the treatment of melanoma. The drug is approved for use in the treatment of inoperable stage IV metastatic melanoma.

Now come results that show for the first time that ipilimumab (at a higher dose) is also effective in an adjuvant setting for earlier-stage disease. The final analysis of results from the EORTC 18071 study (abstract LBA9008) show that in patients with high-risk stage III disease, use of ipilimumab after surgery reduces the relative risk for recurrence by about 25%, compared with placebo.

Another of the highlighted studies shows that patients with advanced disease who have stopped responding to ipilimumab may respond to another immunotherapy, the investigational programmed death (PD-1)-targeting antibody MK-3475. Overall, 34% of patients showed a response to the new drug, although there was a higher response among patients who had not been previously treated with ipilimumab (40%), compared with those who had received ipilimumab (28%).

These results come from a large phase 1 study (abstract LBA9000) involving 411 patients with advanced melanoma (of whom 221 had previously been treated with ipilimumab). "This is probably the largest phase 1 trial we have ever conducted in oncology," commented lead author Antoni Ribas, MD, PhD, professor of medicine at the David Geffen School of Medicine at the University of California in Los Angeles.

The combination of ipilimumab with nivolumab, another investigational agent that acts on the programmed death pathway, has already made headlines. At last year's ASCO meeting, the activity shown by the combination was, in a phase 1 trial, described as "truly remarkable." Now that same phrase is being used again, to describe the longer-term results from this same study.

The long-term results (abstract LBA9003) show that the combination of ipilimumab and nivolumab produced an unprecedented median survival of 40 months for patients with advanced melanoma, which is nearly double the overall survival previously reported with either agent alone.

"Just a few years ago, the median survival for patients diagnosed with advanced melanoma was as little as a year or less.... So it's truly remarkable that we're seeing a median survival of over 3 years in this trial," commented lead author Mario Sznol, MD, professor of medical oncology at Yale School of Medicine in New Haven, Connecticut. "Even in the latest era of targeted and immunotherapy agents, the median survival is, on average, only about 16 to 18 months with any new treatment alone."

Novel Approach to Cervical Cancer

Also highlighted was a novel approach to the treatment of cervical cancer, using a human papillomavirus (HPV)-targeted adoptive T-cell therapy (abstract LBA3008). Although this approach is experimental, early results from a small proof-of-principle study show some striking responses: 2 women with widespread metastatic disease had complete remissions after a single treatment and are still cancer free a year later.

This is the first demonstration that adoptive T-cell therapy works in cervical cancer. Previous studies have shown that the approach works in leukemia, melanoma, and sarcoma. The treatment involves taking T-cells from the tumor tissue, expanding them in a laboratory, and then infusing them back into the patient. It is still experimental, but the striking responses that have been seen in some patients have led to a huge interest in this approach, and it is being explored at a number of major cancer centers in the United States.


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