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Efficacy of the PD-L1 inhibitor avelumab in neuroendocrine or aggressive variant prostate cancer: Results from a phase II, single-arm study.

Publication ,  Conference
Brown, LC; Halabi, S; Humeniuk, MS; Wu, Y; Oyekunle, T; Huang, J; Anand, M; Davies, C; Zhang, T; Harrison, MR; George, DJ; Armstrong, AJ
Published in: Journal of Clinical Oncology
February 20, 2021

89 Background: Men with metastatic neuroendocrine/small cell and aggressive variant prostate cancer (NEPC/AVPC) have poor outcomes despite platinum and taxane chemotherapy. These tumors share common features with small cell lung cancer, including higher tumor mutational burden and genomic alterations, and thus may be responsive to immunotherapy. Methods: We conducted a single arm, 2-stage phase II investigator-sponsored trial, (PICK-NEPC, NCT03179410) with the PD-L1 inhibitor avelumab in patients with NEPC/AVPC. NEPC/AVPC was defined either by histologic criteria (neuroendocrine or small cell features) by central pathology review or by aggressive variant clinical criteria (prior progression on abiraterone or enzalutamide with liver metastasis, bulky radiographic progression and low PSA, or high serum LDH). Prior chemotherapy or hormonal therapy was allowed. Avelumab 10 mg/kg IV every 2 weeks was administered until progression or unacceptable toxicity with ongoing ADT. The primary endpoint was overall response rate (ORR) defined by modified PCWG3 and iRECIST criteria. Results: We consented 19 men with AVPC/NEPC, and 15 initiated treatment with avelumab. The median age was 71 (range 51-85), and 27% had neuroendocrine or small cell histology, while 73% met AVPC clinical criteria with adenocarcinoma histology. Men had received a median of two prior systemic therapies (range 1-3) including carboplatin (27%), docetaxel (73%), enzalutamide (67%), and abiraterone (47%). Median PSA was 54 ng/mL (range 0-393) and 73% had liver metastasis. The ORR by iRECIST was 6.7% (95% CI 0-32%) with 1 CR, 0 PRs, 3 (20%) with stable disease, and 11 (73%) with progressive disease. The patient with a CR had NEPC with a CNS metastasis that was found to be MSI-high/TMB-high due to a somatic MSH2 alteration; he finished 12 months of avelumab and maintains a durable CR and undetectable PSA 6 months after completing all therapy including ADT. Median radiographic progression free survival was 1.8 months (95% CI 1.6-2.0 mo) and median time on therapy was 56 days (range 28-356). Median overall survival was 7.4 mo (85% CI 2.8-12.5 mo). Two grade 3 adverse events (abdominal pain due to hepatic disease progression versus immune hepatitis and pericarditis), and one grade 4 (immune hepatitis) adverse event were attributed to avelumab with no grade 5 adverse events. Grade 1 or 2 infusion-related reactions were experienced by 9 (60%). Conclusions: PD-L1 inhibition with avelumab demonstrated limited clinical efficacy in men with metastatic NEPC/AVPC other than in those with MSI-high disease. Further research is needed into mechanisms of immune evasion in NEPC/AVPC to develop novel immunotherapies. Clinical trial information: NCT03179410.

Duke Scholars

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 20, 2021

Volume

39

Issue

6_suppl

Start / End Page

89 / 89

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Brown, L. C., Halabi, S., Humeniuk, M. S., Wu, Y., Oyekunle, T., Huang, J., … Armstrong, A. J. (2021). Efficacy of the PD-L1 inhibitor avelumab in neuroendocrine or aggressive variant prostate cancer: Results from a phase II, single-arm study. In Journal of Clinical Oncology (Vol. 39, pp. 89–89). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2021.39.6_suppl.89
Brown, Landon Carter, Susan Halabi, Michael Sandon Humeniuk, Yuan Wu, Taofik Oyekunle, Jiaoti Huang, Monika Anand, et al. “Efficacy of the PD-L1 inhibitor avelumab in neuroendocrine or aggressive variant prostate cancer: Results from a phase II, single-arm study.” In Journal of Clinical Oncology, 39:89–89. American Society of Clinical Oncology (ASCO), 2021. https://doi.org/10.1200/jco.2021.39.6_suppl.89.
Brown LC, Halabi S, Humeniuk MS, Wu Y, Oyekunle T, Huang J, et al. Efficacy of the PD-L1 inhibitor avelumab in neuroendocrine or aggressive variant prostate cancer: Results from a phase II, single-arm study. In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. 89–89.
Brown, Landon Carter, et al. “Efficacy of the PD-L1 inhibitor avelumab in neuroendocrine or aggressive variant prostate cancer: Results from a phase II, single-arm study.Journal of Clinical Oncology, vol. 39, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 89–89. Crossref, doi:10.1200/jco.2021.39.6_suppl.89.
Brown LC, Halabi S, Humeniuk MS, Wu Y, Oyekunle T, Huang J, Anand M, Davies C, Zhang T, Harrison MR, George DJ, Armstrong AJ. Efficacy of the PD-L1 inhibitor avelumab in neuroendocrine or aggressive variant prostate cancer: Results from a phase II, single-arm study. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. 89–89.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 20, 2021

Volume

39

Issue

6_suppl

Start / End Page

89 / 89

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences