Immunotherapy improves efficacy and safety of patients with HPV positive and negative head and neck cancer: A systematic review and meta-analysis

Galvis, Marisol Miranda; Borges, Gabriel Álvares; Oliveira, Thiago Bueno; Toledo, Isabela Porto de; Castilho, Rogerio M.; Guerra, Eliete Neves Silva; Kowalski, Luiz Paulo; Squarize, Cristiane H.

doi:10.1016/j.critrevonc.2020.102966

Cited by 51 publications

(42 citation statements)

References 45 publications

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“…41 In a recent meta-analysis, patients with p16-positive HNSCC treated with immune checkpoint inhibitors had a favorable OS. 42 This is in line with the CheckRad-CD8 trial, as p16 positivity had a positive predictive value for pCR after induction chemoimmunotherapy.…”

Section: Discussionsupporting

confidence: 82%

Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8

Hecht

Gostian

Eckstein

et al. 2020

J Immunother Cancer

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BackgroundTo determine safety and efficacy of single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab in stage III-IVB head and neck cancer.MethodsPatients received a single cycle of cisplatin 30 mg/m² on days 1–3 and docetaxel 75 mg/m² on day 1 combined with durvalumab 1500 mg fix dose on day 5 and tremelimumab 75 mg fix dose on day 5. Patients with pathologic complete response (pCR) in the rebiopsy after induction treatment or at least 20% increase of intratumoral CD8+ cell density in the rebiopsy compared with baseline entered radioimmunotherapy with concomitant durvalumab/tremelimumab. The objective of this interim analysis was to analyze safety and efficacy of the chemoimmunotherapy-induction treatment before radioimmunotherapy.ResultsA total of 57 patients were enrolled, 56 were treated. Median pretreatment intratumoral CD8+ cell density was 342 cells/mm². After induction treatment, 27 patients (48%) had a pCR in the rebiopsy and further 25 patients (45%) had a relevant increase of intratumoral CD8+ cells (median increase by a factor of 3.0). Adverse event (AE) grade 3–4 appeared in 38 patients (68%) and mainly consisted of leukopenia (43%) and infections (29%). Six patients (11%) developed grade 3–4 immune-related AE. Univariate analysis computed p16 positivity, programmed death ligand 1 immune cell area and intratumoral CD8+ cell density as predictors of pCR. On multivariable analysis, intratumoral CD8+ cell density predicted pCR independently (OR 1.0012 per cell/mm², 95% CI 1.0001 to 1.0022, p=0.016). In peripheral blood CD8+ cells, the coexpression of programmed death protein 1 significantly increased especially in patients with pCR.ConclusionsSingle cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab is feasible and achieves a high biopsy-proven pCR rate.

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Section: Discussionsupporting

confidence: 82%

Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8

Hecht

Gostian

Eckstein

et al. 2020

J Immunother Cancer

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“…Previous work has been published that investigates the relationship between HPV status and response to anti-PD-1/PD-L1 therapy ( 24 , 25 , 50 ). Patel et al.…”

Section: Discussionmentioning

confidence: 99%

“…( 25 ) both showed a trend towards significance for higher response rates in HPV positive vs. HPV negative tumors in patients receiving anti-PD-1/PD-L1 therapy. Additionally, a recent report indicated that immune checkpoint blockade immunotherapy enhances ORR in HPV positive HNSCC patients compared with HPV negative patients ( 50 ). However, a major limitation of this report is that it only included four clinical trials, which does not encompass the full scope of the present literature on the topic.…”

Section: Discussionmentioning

confidence: 99%

Programmed Death-1/Programmed Death-Ligand 1-Axis Blockade in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Stratified by Human Papillomavirus Status: A Systematic Review and Meta-Analysis

Zhu

Maroun

et al. 2021

Front. Immunol.

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BackgroundProgrammed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors have provided clinical benefit to head and neck squamous cell carcinoma (HNSCC) patients in recent clinical trials. However, it remains unclear as to whether human papillomavirus (HPV) status is associated with improved clinical outcome of anti-PD-1 or anti-PD-L1 immunotherapy in HNSCC.MethodsPubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched up to February 28, 2021. Published clinical trials of HNSCC patients treated with only PD-1 or PD-L1 inhibitors were selected. The primary or secondary outcome of these studies included objective response rate (ORR) stratified by HPV status. The pooled odds ratio (OR) and hazard ratio (HR) were estimated using a fixed-effect model.ResultsA total of seven eligible studies comprising 814 patients were included. The ORR of HPV positive HNSCC patients was significantly higher than that of HPV negative HNSCC patients (OR = 1.77; 95%CI = 1.14-2.74; P = 0.01), and this favorable effect occurred in pooled anti-PD-L1 trials (OR = 2.66; 95%CI = 1.16-6.11; P = 0.02). In comparison, the pooled OR was 1.51 in anti-PD-1 trials (95%CI = 0.90-2.54; P = 0.12). Survival analysis indicated that HPV positive HNSCC patients had a lower risk of overall death as compared to HPV negative HNSCC patients (HR = 0.77; 95%CI = 0.60–0.99; P = 0.04).ConclusionsHPV positive HNSCC patients display improved outcomes with PD-1/PD-L1 axis blockade as compared to HPV negative HNSCC patients. These improved outcomes are likely driven to a greater extent by anti-PD-L1 inhibitors. However, randomized controlled trials with greater numbers of patients are needed for validation of these early findings.

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“…(4) From a microenvironmental perspective, the improved clinical response of HPV-related tumors may further be explained by the adaptive immune responses against viral antigens that stimulate potent antitumor immunity [51]. Therefore, patients affected by HPV (+) HNSCC present an improved response to immunotherapy [52]. (5) Lastly, the clinical profile of patients with HPV (+) tumors, such as younger subjects with fewer comorbidities, favors oncologic management.…”

Section: Hpvmentioning

confidence: 99%

Impacts of Environmental Factors on Head and Neck Cancer Pathogenesis and Progression

Galvis

Loveless

Kowalski

et al. 2021

Cells

Self Cite

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Epidemiological and clinical studies over the past two decades have provided strong evidence that genetic elements interacting with environmental components can individually and collectively influence one’s susceptibility to cancer. In addition to tumorigenic properties, numerous environmental factors, such as nutrition, chemical carcinogens, and tobacco/alcohol consumption, possess pro-invasive and pro-metastatic cancer features. In contrast to traditional cancer treatment, modern therapeutics not only take into account an individual’s genetic makeup but also consider gene–environment interactions. The current review sharpens the focus by elaborating on the impact that environmental factors have on the pathogenesis and progression of head and neck cancer and the underlying molecular mechanisms involved. Recent advances, challenges, and future perspectives in this area of research are also discussed. Inhibiting key environmental drivers of tumor progression should yield survival benefits for patients at any stage of head and neck cancer.

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Immunotherapy improves efficacy and safety of patients with HPV positive and negative head and neck cancer: A systematic review and meta-analysis

Cited by 51 publications

References 45 publications

Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8

Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8

Programmed Death-1/Programmed Death-Ligand 1-Axis Blockade in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Stratified by Human Papillomavirus Status: A Systematic Review and Meta-Analysis

Impacts of Environmental Factors on Head and Neck Cancer Pathogenesis and Progression

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