PD-L1 expression in tumour tissues is widely used to select patients to receive anti-PD-1/PD-L1 antibodies, but data are lacking on the correlation of plasma PD-L1 levels with the effect of treatments.,To investigate the association between PD-L1 mRNA in plasma-derived exosomes and response to nivolumab and pembrolizumab in patients with melanoma (n=18) and NSCLC (n=8), blood was obtained at time point 0 and after 2 months.,Exosomal PD-L1 mRNA was measured by digital droplet PCR.,The mean±s.e.m.,PD-L1 levels in patients with complete and partial responses were 830.4±231.3 and 242.5±82.5 copies per ml at time 0 vs 2 months, respectively (P=0.016).,In patients with stable disease the mean±s.e.m. values were 298.8±97.2 vs 247.5±29.8 copies per ml (P=0.586), while in progressive disease, PD-L1 mRNA levels were 204.0±68.8 vs 416.0±87.8 copies per ml at time 0 vs 2 months, respectively (P=0.001).,This study demonstrates that exosomal PD-L1 is significantly associated with response to treatment.
Patients with primary cutaneous melanomas that are ulcerated and >2 mm in thickness, >4 mm in thickness and those with nodal micrometastases at diagnosis, have few options for adjuvant treatment.,Recent studies have suggested a role for vitamin D to delay melanoma recurrence and improve overall prognosis.,This is a pilot placebo-controlled randomised phase II trial to assess the feasibility, safety and toxicity of an oral loading dose of Vitamin D (500,000 IU) followed by an oral dose of 50,000 IU of Vitamin D monthly for 2 years in patients who have been treated for cutaneous melanoma by wide excision of the primary.,Patients aged 18 - 79 years who have completed primary surgical treatment and have Stage IIb, IIc, IIIa (N1a, N2a) or IIIb (N1a, N2a) disease are eligible for randomisation 2:1 to active treatment or placebo.,The primary endpoints are sufficiency of dose, adherence to study medication and safety of the drug.,The secondary endpoints are participation and progression free survival.,The study has been approved by the Ethics Review Committee (RPAH Zone) of the Sydney Local Health District, protocol number X09-0138.,Effective, non-toxic adjuvant therapy for high risk primary melanoma is not currently available.,Favorable outcomes of this phase II study will form the basis for a multi-centre phase III study to assess whether the addition of oral high-dose vitamin D therapy in patients who have completed primary treatment for melanoma and are at high risk of recurrence will:prolong time to recurrence within 5 yearsimprove overall survival at 5 years andbe both safe and tolerable.,prolong time to recurrence within 5 years,improve overall survival at 5 years and,be both safe and tolerable.,62 patients have been randomised since the study commenced in December 2010.,Target accrual for the study has been met with 75 patients randomised between December 2010 and August 2014.,The Mel-D trial is conducted by the Australia and New Zealand Melanoma Trials Group (ANZMTG 02.09),Australia and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000351213