Neoadjuvant Cytoreductive Treatment With BRAF/MEK Inhibition of Prior Unresectable Regionally Advanced Melanoma to Allow Complete Surgical Resection, REDUCTOR: A Prospective, Single-arm, Open-label Phase II Trial.

Objective: To evaluate the potency of short-term neoadjuvant cytoreductive therapy with dabrafenib plus trametinib (BRAF and MEK inhibitor) to allow for radical surgical resection in patients with unresectable locally advanced melanoma.

Summary Background Data: Approximately 5% of stage III melanoma patients presents with unresectable locally advanced disease, making standard of care with resection followed by adjuvant systemic therapy impossible. Although neoadjuvant targeted therapy has shown promising results in resectable stage III melanoma, its potency to enable surgical resection in patients with primarily unresectable locally advanced stage III melanoma is still unclear.

Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma.

Neoadjuvant ipilimumab plus nivolumab showed high pathologic response rates (pRRs) in patients with macroscopic stage III melanoma in the phase 1b OpACIN ( NCT02437279 ) and phase 2 OpACIN-neo ( NCT02977052 ) studies. While the results are promising, data on the durability of these pathologic responses and baseline biomarkers for response and survival were lacking. After a median follow-up of 4 years, none of the patients with a pathologic response (n = 7/9 patients) in the OpACIN study had relapsed.

Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma.

Adjuvant ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) both improve relapse-free survival of stage III melanoma patients. In stage IV disease, the combination of ipilimumab + nivolumab is superior to ipilimumab alone and also appears to be more effective than nivolumab monotherapy. Preclinical work suggests that neoadjuvant application of checkpoint inhibitors may be superior to adjuvant therapy.

The effect of seasonal variation and secretion of sunitinib in sweat on the development of hand-foot syndrome.

Background: Hand-foot syndrome (HFS) is a side effect of sunitinib with considerable impact on quality of life. Seasonal variation and hyperhydrosis are possibly correlated to occurrence of HFS. Therefore, we proposed to study the prevalence of HFS in different seasons retrospectively and to study the relationship between sunitinib sweat secretion and HFS prospectively.

Determination of sunitinib and its active metabolite N-desethylsunitinib in sweat of a patient.

Skin reactions are side effects of sunitinib therapy with an adverse impact on quality of life often necessitating dose reductions. For conventional antineoplastic agents, such as doxorubicin, previous studies have indicated a possible relationship between sweat excretion and the development of skin toxicity. However, the determination of sunitinib and its active metabolite in sweat has not yet been reported.