Saturday, June 10, 2017

ASCO 2017: Hypofractionated radiotherapy with nivo or pembro in melanoma

Y'all know I've been yelling about combining radiation WITH immunotherapy for YEARSSSSS...

Here's a link to about 10 zillion posts:  Radiation and immunotherapy in melanoma

Here, hypofractionated radiotherapy (multiple small doses of radiation) is combined with anti-PD-1 as a single agent ~

Efficacy of combined hypofractionated radiotherapy and anti-PD-1 monotherapy in patients with melanoma.
ASCO 2017. J Clin Oncol 35, 2017. Roger, Finet, Brou, et al.

Background: Information on the role and type of radiotherapy in melanoma pts treated with anti-PD1 is limited. We report a cohort of advanced melanoma pts having received simultaneous hypofractionated radiotherapy and anti-PD-1 monotherapy. Methods: Database search in the prospective database of a referral center with standardized radiotherapy procedures for all pts having received both treatments between 1/1/15-30/6/16. Radiologists performed independent tumor evaluations (RECIST 1.1) every 3 m, both on radiated and non-radiated lesions. Results: 25 pts with inoperable AJCC stage 3-4 melanoma, mean age 60.5 Y. Anti-PD-1 monotherapy was first systemic treatment in only 40% of pts. Median follow-up after onset of anti-PD-1 therapy (83% nivolumab, 17% pembrolizumab) was 13.3 m, with 48% of pts still alive at last follow-up. Radiotherapy was performed either early (within first 3 m of PD-1 blockade) in pts with rapidly progressing symptomatic lesion(s) (60% of pts) or late (greater than 3 months) in pts with slow progression or dissociated response (40% of pts). It consisted of 1 weekly radiation during 4-5 w (84% of pts), or 1 gammaknife radiation for cerebral mets (16% of pts). Median delay between onset of PD-1 blockade and radiotherapy was 1.8 m (range 0.5-11 m). For radiated lesions, rates of complete (CR), partial (PR) responses, stabilization (S) or progression (P) were 24%, 8%, 44%, and 28%, respectively. For non-radiated lesions (84% of pts), rates of CR, PR, S, and P were 29%, 19%, 19%, and 33%, respectively. Among pts radiated late for insufficient response to anti-PD-1 monotherapy, CR or PR in non-radiated lesions (i.e. abscopal response) was observed in 56% of pts. Anti-PD-1 therapy could be discontinued in 4 pts with CR, without relapse to date. No unusual adverse event was recorded. Conclusions: Hypofractionated radiotherapy may enhance anti-PD1 monotherapy efficacy in difficult-to-treat pts. Controlled studies are needed.

25 patients with inoperable Stage 3/4 melanoma.  40% has anti-PD-1 alone as first therapy (83% nivo, 17% pembro).  Radiation was performed either within the first 3 months of anti-PD-1 treatment in patients with rapidly progressing disease (60% of pts) or after three months of therapy in patients with slow progression (40%).  Radiation was 1 weekly session for 4-5 weeks (84% of patients) or one gammaknife treatment for patients with brain mets (16%).
Lesions that were radiated showed:  CR = 24% , PR = 8% , S = 44%, P = 28%. 
Lesions not treated with radiation:    CR = 29%, PR = 19%, S = 19%, P = 33%.
"Among pts radiated late for insufficient response to anti-PD-1 monotherapy, CR or PR in non-radiated lesions (i.e. abscopal response) was observed in 56% of pts."

That abscopal shit be real, y'all!!!! Thanks ratties! - c

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