With the introduction of novel immune therapeutics for the treatment of disseminated malignancies, we sought to evaluate whether deliberate sequencing
before/after conventional cytotoxic chemotherapy
would have an impact on clinical outcomes in patients with previously treated metastatic melanoma
. We sought to evaluate whether or not ipilimumab immunotherapy
administered before or after cytotoxic chemotherapy
(nab-paclitaxel+bevacizumab, AB) would impact clinical outcomes.
We conducted a randomized phase 2 clinical trial of patients with BRAF wild-type metastatic melanoma
(up to 2 prior therapies) who received either: (A) AB followed by ipilimumab therapy at progression; or (B) ipilimumab followed by AB treatment at progression. The primary goal of the study was a comparison of AB versus ipilimumab progression-free survival, with secondary clinical and laboratory endpoints.
This study did not reach full accrual due to concurrent Food and Drug Administration approval of anti-programmed cell death 1 agents. Nevertheless, the available data suggests a cumulative therapeutic advantage to the sequential use of ipilimumab followed by AB. Correlative laboratory data revealed a favorable effect on systemic immune homeostasis in patients receiving AB therapy, of potential interest in further investigations, especially in the context of chemotherapy
Albeit limited in scope, our data suggest that cytotoxic therapy with nab-paclitaxel and bevacizumab appear to favorably alter systemic parameters of immune function of potential benefit in combination T-cell directed immune checkpoint inhibitor therapy.