Page 48
Figure 44 : Targeted vs . MTR therapy
Source : goetzpartners Research
Radiopharmaceutical combinations are potential blockbusters
Sustained benefits limited to a minority of patients in some cancers
Localised but non-exclusive targeting yields broader cancer kill
Radiopharmaceutical-immuno-oncology combinations open the benefits of immunotherapy to more patients in a greater number of cancers . While immunotherapy raised the patient survival tail dramatically , it is still limited to a minority of patients in a few cancers , thus identification of further immunotherapeutic combinations with superior patient response is imperative . Evidence suggests radiopharmaceuticals could be an effective combination for immunotherapy by boosting anti-cancer immunity throughout the body as well as at their specific site of action . The ability of tumours to escape or acquire resistance to the immune system appears to be tightly connected to both the mutational load of the cancer , as well as the TME . While the mutational load can impact immune recognition by increasing the number of abnormal / altered markers on the tumour cell surface , an inflamed TME is likely to be filled with activated immune cells poised to attack the cancer if immune cells can overcome cancer-cell derived inhibitory signals , tipping the balance in favour of anti-tumour immunogenicity .
Figure
45 : Radiotherapy-immunotherapy combinations ( red ) have a large impact on improving patient survival
Dramatic effects of immunocheckpoint inhibitors
Source : Adapted from ( Immuno-oncology combinations : raising the tail of the survival curve , 2016 )
Potential synergy between radiopharmaceuticals and immune therapy
The potential synergy between radio- and immune therapy has been recently reviewed ( De Martino , Daviaud , & Vanpouille-Box , 2021 ). Exposing the tumour to radiation can boost the number of cancer antigens as well as inflame the tumour microenvironment by stimulating the release of pro-inflammatory signals ( cytokines ) that attract immune cells to the TME and activate anti-tumour cell functions . Localised radiation has also been shown to generate immune effects on tumour sites at a distance from the irradiated tissue . These effects are generated by the dying irradiated tumour cells releasing factors and antigens that promote a systemic immune response that attacks tumour cells
Please see analyst certifications , important disclosure information , and information regarding the status of analysts on pages 91-94 of this research report .