Sarcoma shutdown.

If sarcoma had voicemail, it’d ask you to please leave a message with your clinical trial ideas because the big 3 of immunotherapies has been holding that domain hostage for the past few years. This summer brought us an almost across the board failure with single agent pembrolizumab. Now nivolumab has taken its shot with its own phase 2 trial reported this week in the Lancet. Patients with advanced sarcoma were randomized to 4 cycles of second (or third or fourth) line nivolumab +/- its partner in crime (i.e., another drug owned by the same company) ipilimumab. This was followed by nivo monotherapy for up to 2 years in all patients. The primary endpoint of objective response was achieved by only 6/38 in the combo nivo + ipi group and a whopping 2/38 in the mono nivo group. On the bright side, grade 3-4 toxicity rates with combo therapy was less than one-third the rate seen with melanoma, perhaps because the ipi dose here was one-third (1 mg/kg) that used for melanoma (3 mg/kg). The takeaway: if we can’t learn to compromise on our “one-treatment-fits-all” approach, meaningful progress in the systemic treatment of sarcoma will be shut down for years to come.