Cancer immunotherapy

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Xagena Newsletter
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Advanced melanoma: clinical characteristics predictive of response to Pembrolizumab

Anti-PD-1 therapy has shown significant clinical activity in advanced melanoma and in other cancers. Factors predictive of response remain vaguely defined.

Researchers have reported on clinical characteristics correlated with higher response rates to therapy in a phase I trial of Pembrolizumab ( Keytruda ).

Advanced melanoma patients ( n = 110, enrolled Dec 2011 to Oct 2013, data analysis July 2014 ) received Pembrolizumab in 1 of 3 dosing regimens: 2Q3W, 10Q3W, or 10Q2W.
Tumor responses were evaluated by RECIST 1.1 criteria.
Sites of metastases were determined based on CT imaging, and this analysis was not limited to RECIST target lesions.

In this cohort, overall response rate ( ORR ) to Pembrolizumab was 40%.

Factors correlated with significantly higher ORR were: LDH ( lactate dehydrogenase ) less than or equal to normal ( ORR 52.2% ), no previous Ipilimumab ( ORR 48.3% ), and presence of lung metastasis ( ORR 52.8% ).

Patients with liver metastasis had worse response ( ORR 18.4% ), as did those with liver and lung metastases ( ORR 31.3% ).

In conclusion, normal LDH, no previous Ipilimumab, and presence of lung metastasis are correlated with better response to Pembrolizumab in advanced melanoma patients.
The presence of liver metastasis is correlated with lower response to Pembrolizumab, both in the presence and absence of lung metastasis.
These correlations were observed regardless of BRAF status, presence of brain metastasis, or site of primary melanoma ( cutaneous versus uveal ). ( Xagena )

Tsai KK et al, J Clin Oncol 33, 2015 (suppl; abstr 9031)