Window of opportunity trials in head and neck cancer

Farlow, Janice L.; Birkeland, Andrew C.; Swiecicki, Paul; Brenner, J. Chad; Spector, Matthew E.

doi:10.20517/2394-4722.2018.100

Cited by 9 publications

(6 citation statements)

References 37 publications

(56 reference statements)

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“…24 Patients presenting with resectable oral cavity squamous cell carcinoma (OCSCC) represent a unique population whose primary tumors are relatively accessible to biopsies, and short treatment and assessment windows will not compromise curative intent, standard of care therapies. 25 26 Clinical trials evaluating investigational agents in this patient population offer a 'window-of-opportunity' (WOO) to examine molecular endpoints and pharmacodynamic effects of novel drugs or drug combinations. SNOW is a biomarker-driven WOO study designed to evaluate the immunologic and molecular effects of preoperative sitravatinib and nivolumab in patients with resectable OCSCC.…”

Section: Introductionmentioning

confidence: 99%

Antitumor immune effects of preoperative sitravatinib and nivolumab in oral cavity cancer: SNOW window-of-opportunity study

Oliva

Chepeha

Araújo

et al. 2021

J Immunother Cancer

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BackgroundSitravatinib, a tyrosine kinase inhibitor that targets TYRO3, AXL, MERTK and the VEGF receptor family, is predicted to increase the M1 to M2-polarized tumor-associated macrophages ratio in the tumor microenvironment and have synergistic antitumor activity in combination with anti-programmed death-1/ligand-1 agents. SNOW is a window-of-opportunity study designed to evaluate the immune and molecular effects of preoperative sitravatinib and nivolumab in patients with oral cavity squamous cell carcinoma.MethodsPatients with newly-diagnosed untreated T2-4a, N0-2 or T1 >1 cm-N2 oral cavity carcinomas were eligible. All patients received sitravatinib 120 mg daily from day 1 up to 48 hours pre-surgery and one dose of nivolumab 240 mg on day 15. Surgery was planned between day 23 and 30. Standard of care adjuvant radiotherapy was given based on clinical stage. Tumor photographs, fresh tumor biopsies and blood samples were collected at baseline, at day 15 after sitravatinib alone, and at surgery after sitravatinib–nivolumab combination. Tumor flow cytometry, multiplex immunofluorescence staining and single-cell RNA sequencing (scRNAseq) were performed on tumor biopsies to study changes in immune-cell populations. Tumor whole-exome sequencing and circulating tumor DNA and cell-free DNA were evaluated at each time point.ResultsTen patients were included. Grade 3 toxicity occurred in one patient (hypertension); one patient required sitravatinib dose reduction, and one patient required discontinuation and surgery delay due to G2 thrombocytopenia. Nine patients had clinical-to-pathological downstaging, with one complete response. Independent pathological treatment response (PTR) assessment confirmed a complete PTR and two major PTRs. With a median follow-up of 21 months, all patients are alive with no recurrence. Circulating tumor DNA and cell-free DNA dynamics correlated with clinical and pathological response and distinguished two patient groups with different tumor biological behavior after sitravatinib alone (1A) versus sitravatinib–nivolumab (1B). Tumor immunophenotyping and scRNAseq analyses revealed differential changes in the expression of immune cell populations and sitravatinib-targeted and hypoxia-related genes in group 1A vs 1B patients.ConclusionsThe SNOW study shows sitravatinib plus nivolumab is safe and leads to deep clinical and pathological responses in oral cavity carcinomas. Multi-omic biomarker analyses dissect the differential molecular effects of sitravatinib versus the sitravatinib–nivolumab and revealed patients with distinct tumor biology behavior.Trial registration numberNCT03575598.

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Section: Introductionmentioning

confidence: 99%

Antitumor immune effects of preoperative sitravatinib and nivolumab in oral cavity cancer: SNOW window-of-opportunity study

Oliva

Chepeha

Araújo

et al. 2021

J Immunother Cancer

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“…Evidence suggests that HPV‐associated oropharynx tumors respond more readily to systemic therapy 31,32 . Recently, several studies have evaluated the effect of systemic therapy given in a window of opportunity setting in patients with operable HNSCC 33–35 . The treatment toxicity in such window trials is often minimized to reduce delays to extirpative surgery 33–35 .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, several studies have evaluated the effect of systemic therapy given in a window of opportunity setting in patients with operable HNSCC 33–35 . The treatment toxicity in such window trials is often minimized to reduce delays to extirpative surgery 33–35 . Moreover, this method may allow for chemoselection of patients with 17%–52% having a partial treatment response 36 .…”

Section: Discussionmentioning

confidence: 99%

Poor treatment tolerance in head and neck cancer patients with low muscle mass

et al. 2022

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Background We ascertain the role of a low cervical paraspinal skeletal muscle index (CPSMI) as a biomarker for poor treatment tolerance in patients with operable mucosal head and neck squamous cell carcinoma (HNSCC). Methods A prospective cohort of patients with operable HNSCC requiring microvascular reconstruction was evaluated. Low CPSMI was calculated using preoperative CT neck imaging. Poor treatment tolerance, a composite measure of incomplete therapy or severe morbidity/mortality during treatment, was the primary outcome. Results One hundred and twenty‐seven patients underwent extirpative surgery with a mean age was 60.5. Poor treatment tolerance occurred in 71 (56%) patients with 21 not completing recommended adjuvant therapy and 66 having severe treatment‐related morbidity. A low CPSMI was independently associated with poor treatment tolerance (OR 2.49, 95%CI 1.10–5.93) and delay to adjuvant therapy (OR 4.48, 95%CI 1.07–27.6) after adjusting for multiple confounders. Conclusion Low CPSMI was independently associated with poor treatment tolerance in patients with operable HNSCC.

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“…Window of opportunity trials are studies where patients receive one or more new compounds between the time of cancer diagnosis and initiation of standard (mainly surgery) or investigational treatment [61]. It leverages the potentially idle time before treatment is initiated to investigate novel agents without significantly delaying the standard of care therapy [62]. Treatment response assessment can, therefore, be based on pre-and post-investigational treatment imaging and biopsy.…”

Section: Window Of Opportunity Trials Exploring Targeted Agents Including Immunotherapymentioning

confidence: 99%

Contemporary Opportunities in Nonsurgical Management of Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

Huang

Pilar

et al. 2021

Critical Issues in Head and Neck Oncology

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The majority of head and neck squamous cell carcinoma (HNSCC) is now classified into two major types: HPV-mediated [HPV(+)] and HPV-negative [HPV(−)]. Within this paradigm, the 8th edition TNM staging system effected modification about what is considered “locally-advanced” HNSCC. Two phase-III trials (RTOG 1016 and De-ESCALATE HPV) disappointingly showed that cetuximab is not as effective in HPV(+) oropharyngeal cancer (OPC) compared to cisplatin with radiotherapy. The recent NRG HN002 de-escalation trial demonstrated the presence of outcome heterogeneity within “low-risk” HPV(+) OPC, some of which continue to benefit from cisplatin combined with reduced-dose radiotherapy. Moreover, distant metastasis (DM) has consolidated its position as the leading cause of death in HPV(+) OPC and strategies to mitigate it are necessary. Unanswered questions and ongoing-emerging concepts exist in both HPV(+) and HPV– diseases. These include understanding the importance of risk under the rubric of extranodal extension (ENE), including degrees of pathological ENE (pENE), and emerging knowledge about radiologic ENE (rENE). Strategies addressing modification of biological phenomena have become paramount and includes hypoxia modification (such as smoking cessation). In addition, contemporary evidence suggests that immunotherapy improves survival in recurrent/metastatic settings, and it is now also being explored in primary disease presentations in combination with (chemo-)radiotherapy. Induction chemotherapy achieves DM reduction in nasopharyngeal cancer but has only been explored minimally in HPV(+) OPC. Evidence that loco-regional management can be de-intensified following a favorable response to induction treatment would provide an attractive option for HPV(+) OPSCC patients while also addressing risk of developing distant disease.

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Window of opportunity trials in head and neck cancer

Cited by 9 publications

References 37 publications

Antitumor immune effects of preoperative sitravatinib and nivolumab in oral cavity cancer: SNOW window-of-opportunity study

Antitumor immune effects of preoperative sitravatinib and nivolumab in oral cavity cancer: SNOW window-of-opportunity study

Poor treatment tolerance in head and neck cancer patients with low muscle mass

Contemporary Opportunities in Nonsurgical Management of Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

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