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RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor.

  • Author(s): Brzezniak, Christina
  • Oronsky, Bryan
  • Trepel, Jane
  • Summers, Thomas A
  • Cabrales, Pedro
  • Lee, Min-Jung
  • Day, Regina
  • Jha, Saheli
  • Caroen, Scott
  • Zeman, Karen
  • Ferry, Lindsey
  • Harmer, Cindy
  • Oronsky, Neil
  • Lybeck, Michelle
  • Lybeck, Harry E
  • Brown, James F
  • Reid, Tony R
  • Carter, Corey A
  • et al.

Published Web Location

https://doi.org/10.1159/000464101
Abstract

Small cell carcinoma of the vagina is rare, so rare in fact that the total number reported in English-language journals is less than 30. Due to this extremely low incidence, no specific treatment guidelines have been established, and most of what is clinically known is derived from a handful of single case reports. However, as befitting its highly aggressive histologic features, which are reminiscent of small cell lung cancer (SCLC), first-line treatment is modeled after SCLC. Herein is reported the case of a 51-year-old African-American patient with metastatic biopsy-proven small cell carcinoma of the vagina that progressed through multiple therapies: first-line cisplatin and etoposide (making it platinum-resistant) and radiotherapy, followed by the tumor macrophage-stimulating agent RRx-001 in a clinical trial called QUADRUPLE THREAT, which per protocol preceded a mandated rechallenge with cisplatin and etoposide. RECIST v.1.1 tumor progression on both RRx-001 and cisplatin/etoposide was accompanied by central necrosis in several of the enlarged lymph nodes and hepatic metastases, which may have been evidence of pseudoprogression, accounting for her ongoing longer-than-expected survival, since the necrotic tissue may have primed the activity of the PD-1 inhibitor. The lack of response to RRx-001 is hypothesized to have correlated with sparse tumor macrophage infiltration, seen on pre- and post-treatment biopsies, since the mechanism of action of RRx-001 relates to stimulation of tumor-associated macrophages.

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