Exceptional Response To Pd-L1 Inhibitor After Radiation Therapy In A Patient With Small Cell Neuroendocrine Tumor Of The Prostate Gland Refractory To Combination Treatment With Pd-1 And Ctla-4 Inhibitors.

Abstract Background: Immune checkpoint inhibitor (ICI) treatment became the new treatment paradigm of a wide spectrum of cancers in the last decade. However, overcoming unresponsiveness to ICI remains an important high unmet need in the field of immuno-oncology. It is unclear whether another ICI can be an effective treatment option in patients with tumors refractory to combinatorial immunotherapy. Here we describe a case in whom a significant response to a PD-L1 inhibitor was demonstrated when used concurrently with radiation therapy. Notably, this patient was found to be unresponsive to the combined ICI treatment of PD-1 and CTLA-4 inhibitors. Case Presentation: A 42 y.o. male patient who presented with urinary frequency and hematospermia was diagnosed with stage IV small cell neuroendocrine cancer of prostate gland with osseous metastasis. He was treated with cisplatin plus etoposide for 4 cycles and was subsequently treated with topotecan for 4 cycles given progression of disease (PD). He was given the combination of ipilimumab and nivolumab after another PD. Treatment was discontinued 5 months later due to a lack of response. Two months later, the patient received radiation therapy: 3000 cGy to the prostate and lower pelvis and palliative radiation therapy to the left femur. The patient subsequently underwent multiple lines of treatment with no satisfactory response. Follow up imaging test was concerning for progression with new liver and lung lesions. The treatment was switched to atezolizumab and nab-paclitaxel combination regimen. Concurrently, the patient had stereotactic ablative radiotherapy (4000 cGy) to pelvic region, paraspinal region and para-aortic LNs. Repeated imaging test after two months of the treatment showed an increase in pulmonary nodule size and the treatment was continued despite PD. The repeated scan after 6 weeks revealed an exceptional response that was close to resolution of the metastasized lesion in the liver and significant decrease in size of pulmonary metastatic lesions. Conclusion:This case illustrates the abscopal effect of targeted radiation treatment when coupled with immunotherapy. Exceptional responses seen in non-radiated lesions including lungs and liver after radiation to pelvic lymph nodes while on PD-L1 inhibitors corroborates the concept of synergistic effect of radiation and immunotherapy. Intriguingly, this concurrent treatment approach maximizing the abscopal effect was effective in this case where combinatorial immunotherapy with nivolumab and ipilimumab was ineffective. Future clinical trials are warranted to validate these findings in a more systematic fashion. Citation Format: Leeseul Kim, William Cheng, Yeun Ho Lee, Myungwoo Nam, Won Kyung Hur, Jin Young Hwang, Yoonhee Choi, William H Bae, Cyra Y. Kang, Heayoon Shauna Cho, Emma Yu, Chan Mi Jung, Eugene Kim, Christmann Low, Young Kwang Chae. Exceptional response to PD-L1 inhibitor after radiation therapy in a patient with small cell neuroendocrine tumor of the prostate gland refractory to combination treatment with PD-1 and CTLA-4 inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 678.