Neoadjuvant combination checkpoint blockade trial yields high response rates for patients with high-risk stage three melanoma
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Combination checkpoint blockade before surgery (neoadjuvant therapy) produced a high response rate among patients with high-risk stage 3 melanoma, with nearly half having no sign of disease at surgery, but a high incidence of side effects caused the trial to be closed early.

The phase II study was led by researchers at The University of Texas MD Anderson Cancer Center. Results of the study, the first randomized neoadjuvant clinical trial of immune checkpoint blockade for melanoma patients, are reported in Nature Medicine.

Patients received either the PD-1 inhibitor nivolumab or the combination of nivolumab and the CTLA-4 checkpoint inhibitor ipilimumab. Each drug blocks a separate off-switch on T cells, freeing the immune system to attack cancer. All patients received nivolumab after surgery.

On the combination arm, 8 of 11 (73 percent) patients had their tumors shrink, 5 (45 percent) had no evidence of disease at surgery (pathological complete response), and 73 percent had grade 3 side effects, causing dose delays in 64 percent and delaying surgery for some. There were no grade 4 side effects.

In the nivolumab arm, 3 of 12 (25 percent) had their tumors shrink and had pathological complete response, only 8 percent had grade 3 side effects. Two patients progressed

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