8/16/2023 0 Comments Radium 223 dichlorideRadium-223 dichloride (radium-223) has been approved for the treatment of patients with CRPC and symptomatic bone metastases but without known visceral metastatic disease ( 19, 20). Thus, we hypothesized that the combination of radiotherapy and cancer immunotherapy would have synergistic potential ( 18). As there have been reports of partial or complete eradication of tumors distant from the local radiation field (i.e., abscopal effect) in patients receiving both anti–CTLA-4 and local radiotherapy ( 14–16), the concurrent administration of PD-L1 antibodies may enhance the efficacy of ionizing radiation through a mechanism dependent on cytotoxic T cells ( 17, 18). Cancer immunotherapy monotherapy has not demonstrated dramatic response rates in mCRPC therefore, searches for combination treatments have been undertaken ( 12, 13). Single-agent PD-1 inhibition has shown limited activity in men with chemorefractory mCRPC and measurable disease however, the observed objective response rate (ORR) was a modest 5%, while ≥ 50% decrease in PSA level was seen in only 9% of patients, and radiographic progression-free survival (rPFS) ranged from 2.1 to 3.7 months ( 11). PD-L1 has been shown to be upregulated on tumors and dendritic cells, and to a lesser extent on macrophages, following radiotherapy ( 9, 10). Checkpoint inhibitors in particular appear promising for prostate cancer. IntroductionĬancer immunotherapy is used to treat a wide range of cancer types. Therefore, further development of this combination in the studied patient population does not seem to be justified. The combination of approved doses of atezolizumab and radium-223 used in various dosing schedules did not demonstrate improved clinical efficacy and led to increased treatment-related toxicities. ![]() ![]() To test this hypothesis, we conducted a phase Ib study evaluating the safety and clinical activity of the anti–PD-L1 immune checkpoint inhibitor atezolizumab combined with radium-223 dichloride (radium-223), a systemically administered radiopharmaceutical indicated for patients with metastatic castration-resistant prostate cancer and bone metastases. We hypothesized that adding immune checkpoint inhibitors to radiotherapy might enhance systemic anti-tumor immune responses. Immune checkpoint inhibitors may provide benefit in this setting, particularly when combined with therapies with complementary mechanisms of action. Patients with metastatic castration-resistant prostate cancer face significant morbidity from bone and lymph node and/or visceral metastases and have limited treatment options after progressing on hormonal therapy and chemotherapy.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |