Cabozantinib combination therapy for the treatment of solid tumors: a systematic review

Castellano, Daniel; Apolo, Andrea B.; Porta, Camillo; Capdevila, Jaume; Viteri, Santiago; Rodríguez‐Antona, Cristina; Martin, Lidia; Maroto, Pablo

doi:10.1177/17588359221108691

Cited by 3 publications

(1 citation statement)

References 81 publications

(336 reference statements)

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“…The combination of novel anti-PD-L1 antibodies such as atezolizumab with novel anti-CTLA4 agents such as cabozantinib is also being tested in phase 3 clinical trials (NCT04446117), in CRPC patients previously treated with abiraterone or enzalutamide [78,165]. Clinical trials that test the efficacy of pembrolizumab with enzalutamide are recruiting patients with advanced hormonal-sensitive PCa (KEYNOTE-991: NCT04191096) and metastatic CRPC (KEYNOTE-641: NCT03834493) [26].…”

Section: Future Therapeutic Perspectives and Emerging Biomarkersmentioning

confidence: 99%

DNA Damage Repair Pathways in Prostate Cancer: A Narrative Review of Molecular Mechanisms, Emerging Biomarkers and Therapeutic Targets in Precision Oncology

Grypari

Tzelepi

Gyftopoulos

2023

IJMS

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Prostate cancer (PCa) has a distinct molecular signature, including characteristic chromosomal translocations, gene deletions and defective DNA damage repair mechanisms. One crucial pathway involved is homologous recombination deficiency (HRD) and it is found in almost 20% of metastatic castrate-resistant PCa (mCRPC). Inherited/germline mutations are associated with a hereditary predisposition to early PCa development and aggressive behavior. BRCA2, ATM and CHECK2 are the most frequently HRD-mutated genes. BRCA2-mutated tumors have unfavorable clinical and pathological characteristics, such as intraductal carcinoma. PARP inhibitors, due to the induction of synthetic lethality, have been therapeutically approved for mCRPC with HRD alterations. Mutations are detected in metastatic tissue, while a liquid biopsy is utilized during follow-up, recognizing acquired resistance mechanisms. The mismatch repair (MMR) pathway is another DNA repair mechanism implicated in carcinogenesis, although only 5% of metastatic PCa is affected. It is associated with aggressive disease. PD-1 inhibitors have been used in MMR-deficient tumors; thus, the MMR status should be tested in all metastatic PCa cases. A surrogate marker of defective DNA repair mechanisms is the tumor mutational burden. PDL-1 expression and intratumoral lymphocytes have ambivalent predictive value. Few experimental molecules have been so far proposed as potential biomarkers. Future research may further elucidate the role of DNA damage pathways in PCa, revealing new therapeutic targets and predictive biomarkers.

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Section: Future Therapeutic Perspectives and Emerging Biomarkersmentioning

confidence: 99%

DNA Damage Repair Pathways in Prostate Cancer: A Narrative Review of Molecular Mechanisms, Emerging Biomarkers and Therapeutic Targets in Precision Oncology

Grypari

Tzelepi

Gyftopoulos

2023

IJMS

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Phase I Trial of the Multi-kinase Inhibitor Cabozantinib, a CYP3A4 Substrate, plus CYP3A4-Interacting Antiretroviral Therapy in People Living with HIV and Cancer (AMC-087)

Haigentz

Lee

Chiao

et al. 2023

Clinical Cancer Research

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Purpose: To evaluate the safety, pharmacokinetics, and pharmacodynamic effects of cabozantinib, a CYP3A4 substrate, in people living with HIV (PLWH) and cancer receiving antiretrovirals (ARVs). Experimental Design: Patients received a reduced dose of cabozantinib (20 mg PO daily) with strong CYP3A4 inhibitors (ARV ritonavir or non-ARV cobicistat, stratum A), or a standard 60 mg dose with ARVs that are CYP3A4 inducers (efavirenz or etravirine, stratum B) or non-interacting ARVs (stratum C). Initial dose escalation in stratum A and stratum B was performed based on tolerability. Results: 36 patients received cabozantinib plus ARVs, including 20 in stratum A, 9 in B, and 7 in C. The recommended initial cabozantinib dose for stratum A, B, and C were 20, 60, and 60 mg, respectively. Doses of 40 or 60 mg plus CYP3A4 inhibitors in stratum A and 100 mg plus CYP3A4 inducers in stratum B were associated with excessive toxicity, whereas 60 mg with non-interacting ARVs was not. The steady state minimal concentrations were lower at 20 mg in stratum A or 60 mg in stratum B compared to 60 mg in stratum C, while total exposure was only lower in 60 mg in stratum B compared to 60 mg in stratum C. Activity was observed in Kaposi sarcoma and an AXL-amplified sarcoma. Conclusions: Cabozantinib as a single agent should be initiated at 20 mg daily and 60 mg daily when taken concurrently with ARVs that are strong CYP3A4 inhibitors and inducers, respectively, with consideration for subsequent escalation per current cabozantinib guidelines.

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Progression in immunotherapy for advanced prostate cancer

Liang

Liu²,

Guo³

et al. 2023

Front. Oncol.

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Prostate cancer is one of the most common malignant cancers of the male genitourinary system and has high morbidity and mortality. Currently, treatment modalities for localized prostate cancer focus mainly on radical prostatectomy or radical radiation therapy. Some patients still experience disease recurrence or progression after these treatments, while others are already at an advanced stage or have metastases at the time of diagnosis. With the continuous development and progress of medicine in recent years, immunotherapy has become a revolutionary cancer treatment, and has achieved remarkable accomplishments in the treatment of hematologic malignancies. A variety of immunotherapies have also appeared in the field of advanced prostate cancer treatment, including therapeutic vaccines and immune checkpoint therapies. Despite the discrepancy between the results of some immunotherapy studies, immunotherapy for prostate cancer has shown some initial success, especially in combination immunotherapies. Currently, immunotherapy is mainly used in advanced prostate cancer, especially in patients with metastatic castration-resistant prostate cancer. However, with the development of more clinical trials of immunotherapy, more evidence will be provided supporting the rational application of immunotherapy in the future.

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Cabozantinib combination therapy for the treatment of solid tumors: a systematic review

Cited by 3 publications

References 81 publications

DNA Damage Repair Pathways in Prostate Cancer: A Narrative Review of Molecular Mechanisms, Emerging Biomarkers and Therapeutic Targets in Precision Oncology

DNA Damage Repair Pathways in Prostate Cancer: A Narrative Review of Molecular Mechanisms, Emerging Biomarkers and Therapeutic Targets in Precision Oncology

Phase I Trial of the Multi-kinase Inhibitor Cabozantinib, a CYP3A4 Substrate, plus CYP3A4-Interacting Antiretroviral Therapy in People Living with HIV and Cancer (AMC-087)

Progression in immunotherapy for advanced prostate cancer

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