Ipilimumab After Anti-PD-1 Therapy ‘Viable’ For Advanced Melanoma

Advanced melanoma patients may respond to ipilimumab after progressing on nivolumab or pembrolizumab therapy

medwireNews: The CTLA-4 inhibitor ipilimumab is a viable treatment for advanced melanoma patients who have progressed while using anti-programmed cell death-1 (PD-1) agents, suggests a case series review.

“As clinical trials addressing the optimal treatment sequence of immunotherapies and targeted therapies are still lacking, sequential and non-sequential treatment in our study likely reflects the ‘real-world’ clinical practice for patients seen in daily routine”, say Lisa Zimmer, from University Hospital Essen in Germany, and co-workers.

They reviewed medical records for patients at 12 centres with unresectable stage III or IV melanoma who had documented disease progression after interval treatment with nivolumab or pembrolizumab. Many of the patients had also previously been treated with ipilimumab or a BRAF/MEK inhibitor.

The researchers identified 47 patients who were subsequently treated with ipilimumab at a dose of 3 mg/kg every 3 weeks. These patients had an overall response rate (ORR), defined as a complete or partial response, of 16% and a disease control rate, including response and stable disease, of 42%.

These rates are similar to the response data for a phase III clinical trial of first-line ipilimumab, the team writes in the European Journal of Cancer.

The researchers also determined the outcome of 37 patients who were treated with ipilimumab 1 or 3 mg/kg plus nivolumab 1 or 3 mg/kg, giving an ORR of 21% and a disease control rate of 33%.

The median time to progression during treatment was 3 months for both arms and the 1-year overall survival rates were 54% with ipilimumab monotherapy and 55% with combined therapy.

Further analysis showed that 46% of the ipilimumab monotherapy group and 23% of the combination group who had previously experienced progressive disease as their best response to anti-PD-1 therapy derived a benefit from the current treatment.

But of the patients who had previously responded to anti-PD-1 therapy, progressive disease was the best response to the current treatment in 63% of the ipilimumab monotherapy group and 64% of the combination group.

Thus, prior response to anti-PD-1 therapy did not significantly predict the likelihood of patients responding to treatment with ipilimumab or ipilimumab plus nivolumab, the researchers summarise.

“[I]pilimumab should be considered as a viable treatment option for patients with prior failure of anti-PD-1 therapy, including those with [progressive disesase] as best response to prior anti-PD-1, with response rates comparable to treatment-naïve patients”, Lisa Zimmer et al believe.

But noting that the ORR for ipilimumb plus nivolumab was “noticeably lower” than previously reported for treatment-naïve patients, the researchers advise that “caution must be exercised in the use of this combination following failure of single-agent anti-PD-1 therapy” until prospective trial results are available.


Zimmer L, Apuri S, Eroglu Z, et al. Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma. Eur J Cancer2017; 75: 47–55. Advance online publication 17 February. http://dx.doi.org/10.1016/j.ejca.2017.01.009

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