Limited data from clinical trials assessing immunotherapy effects on bone metastases.

Abstract Bone metastases are a significant cause of mortality in many major cancers. They are difficult to treat and their response rate to standard-of-care therapies is low. Immunotherapies have been approved as stand-alone therapies or in combination with other therapies for the treatment of advanced or metastatic breast, prostate and lung cancer and melanoma patients. It is unclear if approved immunotherapies affect bone metastases. In this study, relevant scientific publications were evaluated for feasibility to perform a meta-analysis about immunotherapy efficacy on bone metastases. A PubMed search for approved immunotherapies for each of the above-mentioned cancer indications on September 21, 2020 resulted in 561 relevant scientific publications. From these, the criteria for the selection of publications for this study were: 1) patients had detectable bone metastases, 2) patients received at least one immunotherapy treatment, 3) therapy effects for bone metastases was followed, 4) the study was published between 2010-2020. Based on these criteria only six eligible studies were identified. Treatment with atezolizumab and nab-paclitaxel increased median overall survival in PD-L1+ bone metastatic tripe-negative breast cancer patients compared to nab-paclitaxel treatment only (Schmid et al., 2020). In metastatic castration-resistant prostate cancer patients with bone-predominant disease, pembrolizumab increased disease control rate and median overall survival compared to patients without bone metastases (Antonarakis et al., 2019). In non-small cell lung cancer patients, long-term survivors (LTS, over 24 months) had fewer bone metastases than non-LTS (Pawel et al., 2019). Upon progression, LTS treated with atezolizumab had less cases with liver and bone metastases compared to non-LTS, whereas the incidence was similar in patients treated with docetaxel. In melanoma, complete radiographic responses in bone metastatic patients were not observed when the patients were treated with pembrolizumab (Lee et al., 2017), progressive disease was observed with ipilimumab in combination with radiation therapy (Sundahl et al., 2018), and patients progressed at bone and other metastatic sites with ipilimumab in combination with Bacillicus Calmette-Guérin (Da Gama Duarte et al., 2018). Only about 1% (6/561) of publications with approved immunotherapies in breast, prostate and lung cancer and melanoma patients reported results on bone metastases. No conclusion can be drawn about the efficacy due to the limited number of eligible studies. Clinical trials with immunotherapies specifying effects on bone metastases are warranted as they would allow to better understand metastasis-specific responses, improve patient selection in future clinical studies, and ultimately help in providing more effective treatments for patients with life-threatening bone metastases. Citation Format: Tiina E. Kähkönen, Jussi M. Halleen, Jenni Bernoulli. Limited data from clinical trials assessing immunotherapy effects on bone metastases [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 2870.