Browsing by Subject "PD-1/PD-L1"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Benefits of combination therapy with immune checkpoint inhibitors and predictive role of tumour mutation burden in hepatocellular carcinoma: A systematic review and meta-analysis
    (Elsevier, 2022-11) Zheng, Jiaxi; Shao, Minghai; Yang , Weifang; Ren , Justin; Chen, Xiaofeng; Yang, Haihua; Radiation Oncology, School of Medicine
    Objectives To investigate the clinical benefits of combination therapy with immune checkpoint inhibitors (ICIs) and best combination regimen for people with advanced hepatocellular carcinoma (HCC) and to explore the predictive performance of tumour mutation burden (TMB). Methods We conducted a systematic literature search to identify clinical trials. Meta-analysis and subgroup analyses were performed to estimate the benefits of combination regimens with PD-1/PD-L1 inhibitors for patients with advanced HCC and compare the effectiveness of PD-1/PD-L1 inhibitors and sorafenib as first-line therapy. Individualized analysis and Kaplan-Meier were used to assess the prognostic value of TMB. Results A total of 29 studies with 5396 patients were included. ICIs’ combination therapy had higher ORR (26 % vs 15 %) and DCR (73 % vs 55 %), longer PFS (5.5 vs 3.1 months) and OS (15.9 vs 12.6 months) compared to monotherapy. Anti-PD-1/PD-L1 agents provided improved ORR, DCR, PFS and OS compared to sorafenib. The overall ORs of ORR and DCR in subgroup analysis were 3.49 (95 % CI 2.36–5.17, p < 0.01) and 1.60 (95 % CI 1.15–2.21, p < 0.01). The overall HRs of PFS and OS were 0.68 (95 % CI 0.48–0.96, p = 0.03) and 0.73 (95 % CI 0.62–0.85, p < 0.01). PD-1/PD-L1 inhibitors plus anti-VEGF agents had an advantage in DCR (0.80 vs 0.48, meta-regression = − 0.32, P < 0.001), but an equal ORR (0.29 vs 0.26) compared to dual immune checkpoint inhibitors. The total OS in Dua-ICIs were 16.5 months (95 % CI 14.2–18.7), yet not reached in the major studies of ICI plus anti-VEGF regimen. In individualized analysis, the 1-year OS was superior for patients who had high-TMB (>10, mutations/Mb) than moderate-TMB (1–10, mutations/Mb; 28 % vs 15 %, P = 0.025). Conclusion Immune checkpoint inhibitors’ combination therapy improved clinical outcomes in the management of advanced hepatocellular carcinoma. However, the overall objective response rate still did not exceed 30%. PD-1/PD-L1 inhibitors plus anti-angiogenic agents and dual immunotherapy provided significantly increased survival over sorafenib, which also pose new challenges for future research, and more appropriate and guided control regimens are required. Also, TMB may be a promising prognostic biomarker for immunotherapy in HCC. However, the validation of prospective and large sample studies is needed.
  • Thumbnail Image
    Item
    Recurrent glioma clinical trial, CheckMate-143: the game is not over yet
    (Impact Journals, 2017-10-06) Filley, Anna C.; Henriquez, Mario; Dey, Mahua; Neurological Surgery, School of Medicine
    Glioblastoma (GBM) is the most common, and aggressive, primary brain tumor in adults. With a median patient survival of less than two years, GBM represents one of the biggest therapeutic challenges of the modern era. Even with the best available treatment, recurrence rates are nearly 100% and therapeutic options at the time of relapse are extremely limited. Nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody, has provided significant clinical benefits in the treatment of various advanced cancers and represented a promising therapy for primary and recurrent GBM. CheckMate 143 (NCT 02017717) was the first large randomized clinical trial of PD pathway inhibition in the setting of GBM, including a comparison of nivolumab and the anti-VEGF antibody, bevacizumab, in the treatment of recurrent disease. However, preliminary results, recently announced in a WFNOS 2017 abstract, demonstrated a failure of nivolumab to prolong overall survival of patients with recurrent GBM, and this arm of the trial was prematurely closed. In this review, we discuss the basic concepts underlying the rational to target PD pathway in GBM, address implications of using immune checkpoint inhibitors in central nervous system malignancies, provide a rationale for possible reasons contributing to the failure of nivolumab to prolong survival in patients with recurrent disease, and analyze the future role of immune checkpoint inhibitors in the treatment of GBM.
  • Thumbnail Image
    Item
    Resistance to Systemic Agents in Renal Cell Carcinoma Predict and Overcome Genomic Strategies Adopted by Tumor
    (MDPI, 2019-06-14) Mollica, Veronica; Di Nunno, Vincenzo; Gatto, Lidia; Santoni, Matteo; Scarpelli, Marina; Cimadamore, Alessia; Lopez-Beltran, Antonio; Cheng, Liang; Battelli, Nicola; Montironi, Rodolfo; Massari, Francesco; Pathology & Laboratory Medicine, IU School of Medicine
    The development of new systemic agents has led us into a "golden era" of management of metastatic renal cell carcinoma (RCC). Certainly, the approval of immune-checkpoint inhibitors and the combination of these with targeted compounds has irreversibly changed clinical scenarios. A deeper knowledge of the molecular mechanisms that correlate with tumor development and progression has made this revolution possible. In this amazing era, novel challenges are awaiting us in the clinical management of metastatic RCC. Of these, the development of reliable criteria which are able to predict tumor response to treatment or primary and acquired resistance to systemic treatments still remain an unmet clinical need. Thanks to the availability of data provided by studies evaluating genomic assessments of the disease, this goal may no longer be out of reach. In this review, we summarize current knowledge about genomic alterations related to primary and secondary resistance to target therapy and immune-checkpoint inhibitors in RCC.