PD-1/PD-L1 blockade in cervical cancer: current studies and perspectives
Yumeng Wang1, Guiling Li1,2()
1. Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Fudan University, Shanghai 200011,China 2. Department of Integration of Western and Traditional Medicine, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
Cervical cancer (CC) is the fourth most commonly diagnosed female malignancy and a leading cause of cancer-related mortality worldwide, especially in developing countries. Despite the use of advanced screening and preventive vaccines, more than half of all CC cases are diagnosed at advanced stages, when therapeutic options are extremely limited and side effects are severe. Given these circumstances, new and effective treatments are needed. In recent years, exciting progress has been made in immunotherapies, including the rapid development of immune checkpoint inhibitors. Checkpoint blockades targeting the PD-1/PD-L1 axis have achieved effective clinical responses with acceptable toxicity by suppressing tumor progression and improving survival in several tumor types. In this review, we summarize recent advances in our understanding of the PD-1/PD-L1 signaling pathway, including the expression patterns of PD-1/PD-L1 and potential PD-1/PD-L1-related therapeutic strategies for CC.
*NCT02257528: treating persistent, recurrent, and metastatic CC
Phase II
*NCT02465060: treating patients with mismatch repair deficiency (loss of MLH1 or MSH2 by IHC) in advanced refractory solid tumors
Phase II
*NCT02379520: HPVST cells alone or in combination with nivolumab in HPV-related carcinoma
Phase I
*NCT03126110:INCAGN01876+ nivolumab or/and ipilimumab treating advanced or metastatic malignancies
Phase I/II
*NCT03241173:INCAGN01949+ nivolumab or/and ipilimumab treating advanced or metastatic malignancies
Phase I/II
*NCT03298893: in combination with radiotherapy and cisplatin in locally advanced CC
Phase I
*NCT02628064: treating advanced solid tumors including CC
Phase II
Pembrolizumab (MK3475, Keytruda®)
*NCT02628067: treating advanced solid tumors including CC
Phase II
*NCT02635360: in combination with chemoradiation for the treatment of advanced CC
Phase II
*NCT03144466: in combination with radiotherapy and cisplatin treating advanced CC
Phase I
*NCT03192059: in combination with radiation and an immune modulatory cocktail treating advanced and/refractory CC endometrial carcinoma or uterine sarcoma
Phase II
*NCT02858310: TCR gene therapy targeting HPV-16 E7 with or without pembrolizumab for HPV-associated cancers
Phase I
*NCT03444376: in combination of GX-188E vaccination treating advanced, nonresectable HPV16 and/or 18+ CC
Phase Ib-II
*NCT03635567: in combination with chemotherapy treating persistent, recurrent, or metastatic CC
Phase III
*NCT03367871: in combination with chemotherapy and bevacizumab treating CC
Phase II
PD-L1
Atezolizumab (MDPL-3280A, Tecentrip®)
*NCT02921269: in combination with bevacizumab treating recurrent, persistent, or metastatic CC
Phase II
*NCT03074513: in combination with bevacizumab treating rare solid tumors including CC
Phase II
*NCT03073525: in combination with Vigil treating advanced gynecological cancers
Phase II
*NCT02914470: in combination with carboplatin-cyclophosphamide treating advanced breast cancer and gynecologic cancer
Phase I
*NCT03614949: in combination with stereotactic body radiation therapy treating recurrent, persistent, or metastatic CC
Phase II
*NCT03340376: in combination with doxorubicin treating recurrent CC
Phase II
Avelumab (MSB0010718C, BAVENCIO®)
*NCT03260023: in combination with TG4001 treating HPV-16+ recurrent or metastatic malignancies
Phase I/II
*NCT03217747: in combination with or without radiation, or radiation and cisplatin treating limited, locally advanced or metastatic solid tumors including CC
Phase I/II
Durvalumab (MEDI4736)
*NCT01975831: in combination with tremelimumab treating advanced solid tumors
Phase I
*NCT02725489:in combination with Vigil and durvalumab treating advanced women's cancers
Phase II
*NCT02291055: in combination with ADXS11-001 in previously treated locally advanced or metastatic cervical or HPV+ head and neck cancer
Phase I/II
*NCT03452332: in combination with stereotactic ablative radiotherapy and tremelimumab treating cervical, vaginal, or vulvar cancer
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