Pembro for mucosal melanoma vs response rate to nivo alone vs the ipi/nivo combo

A diagnosis of melanoma is bad enough.  Unfortunately, folks with mucosal melanoma have an even more difficult time.  Here's a review of two articles:

This report (Jan 2017):  Evaluation of response to nivo or ipi/nivo in Cutaneous and Mucosal Melanoma  Notes ~  889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma). Among patients who received nivolumab monotherapy, median progression-free survival was 3.0 months and 6.2 months for mucosal and cutaneous melanoma, with objective response rates of 23.3% and 40.9%, respectively. Median progression-free survival in patients treated with nivolumab combined with ipilimumab was 5.9 months and 11.7 months for mucosal and cutaneous melanoma, with objective response rates of 37.1% and 60.4%, respectively. 

Efficacy of pembrolizumab (pembro) in patients (pts) with advanced mucosal melanoma (mucMEL): data from KEYNOTE-001, 002, and 006. Hamid, Ribas, Hodi, et al.  Society for Melanoma Research 2016 Congress.  Published 29 January 2017. 

Pembro has demonstrated efficacy and a manageable safety profile in advanced MEL. We assessed outcomes of pts with advanced mucMEL enrolled in KEYNOTE-001 (NCT01295827), KEYNOTE-002 (NCT01704287), and KEYNOTE-006 (NCT01866319). Pts received pembro 2 mg/kg Q3W, 10 mg/kg Q3W, or 10 mg/kg Q2W. Response was assessed per RECIST v1.1 by independent central review. Of the 1567 pts in the pembro arms who received greater than/= to 1 pembro dose, 84 (5%) had mucMEL. 57% of pembro-treated pts with mucMEL were women, 49% were aged greater than/= to 65 y, 32% had ECOG PS 1, 48% had elevated LDH, 8% had BRAF^V600 mutant tumors, 81% had M1c disease, 58% had baseline tumor size greater than/= to 77.7 mm (ie, median in total population), and 70% with known PD-L1 status had PD-L1–positive tumors. 90% of pts received greater than/= to1 prior therapy: 37% received 1, 45% received 2, and 8% received greater than/= to 3; 39% received prior ipilimumab (ipi). In pts with mucMEL, ORR was 19%, DCR was 31%, median PFS was 2.8 months, and median OS was 11.3 months. In the 16 responders, median time to response was 12.4 weeks (range, 11.1–84.1), 12 (75%) were alive without subsequent progression, and median response duration was 27.6 months (range 1.1+ to 27.6). In ipi pretreated pts with mucMEL, ORR was 15%, DCR was 27%, 4 of 5 (80%) responders were alive and without subsequent progression, and median response duration was 27.6 months. In the 1483 pembro-treated pts with non-mucMEL, ORR was 33%, DCR was 47%, median time to response was 12.4 weeks (range 3.7–144.0), 72% of responders were alive and progression free, median response duration was NR (range 1.3+ to 38.8+), median PFS was 4.2 months, and median OS was 23.5 months. Pembro is active in advanced mucMEL and provides durable activity regardless of prior ipi.

So...according to these studies:  Folks with mucosal melanoma who were given nivo alone had an objective response rate of 23% (cutaneous melanoma = 40%).  Those with mucosal melanoma given the ipi/nivo combo had a 37% objective response rate (cutaneous = 60%).  With pembro,  folks with mucosal mel not previously treated with ipi the ORR was 19%.  Those with prior ipi had a response rate of 15% to pembro.  (Generally the ORR of patients with cutaneous mel treated with pembro was 33%.)

In the end, folks with cutaneous melanoma can respond to nivo (Opdivo) or pembro (Keytruda) alone (and those responses can be durable).  However, it seems the response rate to the ipi/nivo combo is much better...though none of the response rates are as high as those that can be attained for cutaneous melanoma patients.  Hang in there, ratties.  Wishing you all my best. - c