SPOTLIGHT tumor cells) (551), as well as when given in combination with chemotherapy or radiotherapy (549). Furthermore, researchers are investigating whether combining immunotherapeutics with modulation of the patient’s microbiome (see Targeting the Microbiome in Cancer Treatment, p. 150) will further increase their effectiveness in treating cancer (552). Currently, there are many therapeutic combinations being tested in clinical studies (see Sidebar 41, p. 131). Researchers are continually pioneering different methods to identify and test novel therapeutic combinations that may be more effective and safer to treat cancer, and/or may be able to overcome or delay resistance to cancer treatment. Given that the number of potential combinations of therapies is immense and will increase dramatically as the number of cancer treatments rises in the future, continued research is needed to identify biomarkers to help determine the most effective combinations. Researchers anticipate that big data approaches and machine learning technologies will further accelerate the pace of research in combination therapy for cancer. Mechanism-based rational combinations of different immunotherapeutics or with other treatment modalities have the potential to transform the future of cancer care. Clinical Trials Testing Immunotherapy Combinations with Other Modalities Ongoing research is evaluating the effectiveness of combining immunotherapy with other types of cancer treatments. Here we highlight selected examples of immune checkpoint inhibitor combinations with other types of cancer treatments. CANCER TYPE CLINICAL TRIAL PHASE COMBINATION TREATMENT GROUPS IMPACT OF COMBINATION Advanced HER2-positive gastric cancer (553) III Immunotherapy + molecularly targeted therapy + chemotherapy pembrolizumab + trastuzumab + chemotherapeutic versus trastuzumab + chemotherapeutic Improved overall response HER2-negative stage II/III breast cancer (553) II Immunotherapy + molecularly targeted therapy + chemotherapy durvalumab + olaparib + paclitaxel versus paclitaxel Improved partial response rate Metastatic triple negative breast cancer (554) III Immunotherapy + chemotherapy pembrolizumab + chemotherapy versus chemotherapy Increased overall survival Non-small cell lung cancer; carcinoma (555) II Immunotherapy + radiation therapy pembrolizumab versus pembrolizumab + radiation therapy Improved overall survival SIDEBAR 41 As of December 2021, 4,062 clinical trials (83 percent of all 4,897 active trials) were testing ICIs targeting PD-1/PD-L1 proteins in combination with other immunotherapies, molecularly targeted therapies, chemotherapies, and radiotherapies (548). T CELL ICI PD-L1 PD1 CANCER CELL Immunotherapy: Pushing the Frontier of Cancer Medicine AACR Cancer Progress Report 2023 131
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