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Abbreviated high-dose interferon induction fails to prolong RFS in melanoma
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Patients with surgically resected intermediate-level melanoma who received 4 weeks of high-dose IV interferon induction had identical RFS and OS rates as those who underwent observation, according to a phase 3 randomized study published in Journal of Clinical Oncology.
Further, patients who received high-dose interferon reported more treatment-related toxicities and lower quality of life.
“For interferon to be effective, it might need the additional 11 months, not just the 4 weeks of induction alone,” Sanjiv S. Agarwala, MD, professor of medicine at Temple University School of Medicine, chief of hematology and oncology at St. Luke’s Cancer Center, and a HemOnc Today Editorial Board member, told HemOnc Today.
Interferon was the first agent approved for adjuvant therapy of patients with high-risk surgically resected melanoma and has shown RFS and OS benefits.
In the Eastern Cooperative Oncology Group E1684 trial, patients who received high-dose interferon — which consisted of a 4-week induction period, followed by 12 months of maintenance — had improved RFS (P = .002) and OS (P = .024) compared with patients who underwent observation.
Because the Kaplain-Meier curves showed early separation, researchers hypothesized that the major source of benefit from high-dose interferon regimen may have come in the first 4 weeks of induction treatment.
“We were pretty confident that our hypothesis was correct,” Argawala said. “I really felt, as did many of my colleagues, that the induction [phase] might be it. Subsequently, I’m no longer so surprised because there are other regimens with longer durations of interferon that have shown benefits. Maybe it is a duration issue.”
Agarwala and colleagues randomly assigned 1,150 patients (57% men; 94.2% white; median age, 52 years; 77.7% lymph node negative) to receive high-dose interferon (20 MU/m2) daily for 5 days every week for 4 weeks (n = 581) or observation (n = 569).
Researchers selected patients with T2bN0, T3a-bN0, T4a-bN0 or T1-4N1a-2a disease, because “they were considered to be at intermediate risk for recurrence and particularly likely to be motivated to pursue a shorter and potentially less toxic adjuvant therapy regimen with less disruption of quality of life,” the researchers wrote.
Median follow-up was 7 years.
The primary endpoint was RFS, with secondary endpoints of OS, toxicity and quality of life.
The 5-year RFS rate for the 4-week interferon group was identical to the observation group (0.7; 95% CI, 0.66-0.74). The 5-year OS was almost identical, at 0.83 (95% CI, 0.8-0.86) for the 4-week interferon group and 0.83 (95% CI, 0.79-0.86) for the observation group.
More patients in the 4-week interferon group experienced treatment-related grade 3 and worse toxicity (57.9% vs. 4.6%; P < .001). Those in the 4-week interferon group also reported lower quality-of-life scores.
“The takeaway from this is that you may not need to do the intensive phase at all,” Agarwala said. “If the intensive phase by itself is not working and it’s a duration issue, then perhaps we should drop the intensive phase and give long durations of interferon treatment. It may be too much intensity for a nonbeneficial regimen to put people through 4 weeks of intensive induction treatment, where they have to come to the office every day for an IV treatment and basically take that entire month off from work.”
Agarwala said he hopes this trial will provide further guidance for physicians and patients to help negotiate the complexity of choices that are available for the adjuvant therapy of high-risk melanoma.
“The field is moving forward nicely, and it is very possible that in the near future we might not be using interferon at all because drugs like ipilimumab [Yervoy, Bristol-Myers Squibb] and PD-1 inhibitors in clinical trials now might play a bigger role in the future,” he said. “We need to look forward and interferon’s days may be numbered, so to speak.”– by Chuck Gormley
For more information:
Sanjiv S. Agarwala, MD, can be reached at Saint Luke’s Cancer Center, 1600 Riverside Circle, Easton, PA, 18045; email: ssagarwala0501@gmail.com.
Disclosure: Agarwala reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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