LBA35 Avelumab-cetuximab-radiotherapy versus standards of care in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): Randomized phase III GORTEC-REACH trial

Bourhis, Jean; Tao, Yungan; Sun, Xin; Siré, C.; Martin, Laurent; Liem, X.; Coutté, Alexandre; Pointreau, Y.; Thariat, Juliette; Miroir, J.; Rolland, F.; Kaminsky, M-C; Borel, Christian; Maillard, Aline; Sinigaglia, Laura; Guigay, J.; Saada-Bouzid, E.; Even, C.; Aupérin, Anne

doi:10.1016/j.annonc.2021.08.2112

Cited by 48 publications

(23 citation statements)

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“…Early results from these trials are indicative that hypofractionated RT can induce a larger immune response and enhance the effects of immunotherapy compared to conventional RT 4,15 (NCT03635164). As all clinical trials using immunotherapies combined with traditional RT have failed in HNSCC 4,55 , we expect that these findings will be of high translational relevance in the setting of hypofractionated RT. Despite these limitations, our data strongly support future HNSCC clinical trial design with lymphatic sparing approaches and hypofractionated RT, particularly in the context of immunotherapy.…”

Section: Discussionmentioning

confidence: 96%

Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors

et al. 2022

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In the setting of conventional radiation therapy, even when combined with immunotherapy, head and neck cancer often recurs locally and regionally. Elective nodal irradiation (ENI) is commonly employed to decrease regional recurrence. Given our developing understanding that immune cells are radio-sensitive, and that T cell priming occurs in the draining lymph nodes (DLNs), we hypothesize that radiation therapy directed at the primary tumor only will increase the effectiveness of immunotherapies. We find that ENI increases local, distant, and metastatic tumor growth. Multi-compartmental analysis of the primary/distant tumor, the DLNs, and the blood shows that ENI decreases the immune response systemically. Additionally, we find that ENI decreases antigen-specific T cells and epitope spreading. Treating the primary tumor with radiation and immunotherapy, however, fails to reduce regional recurrence, but this is reversed by either concurrent sentinel lymph node resection or irradiation. Our data support using lymphatic sparing radiation therapy for head and neck cancer.

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Section: Discussionmentioning

confidence: 96%

Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors

et al. 2022

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“…With the future looking into immunotherapy (immune checkpoint inhibitor drugs targeting PD-1or PD-L1), a novel concept of combining immunotherapy with anti-EGFR agent and RT is hypothesized as anti-EGFR agents also act by immune modulation. The REACH study by the GORTEC group - Randomized Trial of Avelumab-Cetuximab-Radiotherapy Versus standard of care (CCRT) in LA-HNC, whose interim data was recently presented as an abstract [55] , showed that the combination of anti PD-L1 – Avelumab plus Cetuximab and RT did not improve PFS (1 year PFS 64% v/s 73%; HR-1.27) and was found to be futile when compared to standard of care, especially in the cohort which used Cisplatin based CCRT.…”

Section: Discussionmentioning

confidence: 99%

The dogma of Cetuximab and Radiotherapy in head and neck cancer – A dawn to dusk journey

Krishnamurthy¹,

Ahmed²,

Bhise³

et al. 2022

Clinical and Translational Radiation Oncology

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“…Although there are ongoing trials with combination approaches using immunotherapy, the vast majority of them use immunotherapy in combination with chemotherapy in the metastatic setting or after chemoradiation in the adjuvant setting. The recent JAVELIN Head and Neck 100 and GORTEC‐REACH trials investigated avelumab with chemoradiation in locally advanced HNSCC, but failed to meet their primary PFS endpoints 19–21 . However, the majority of patients in each study had oropharyngeal cancer, which could have masked the benefit of concurrent immunotherapy given the more favorable prognosis at this subsite.…”

Section: Discussionmentioning

confidence: 99%

“…The recent JAVELIN Head and Neck 100 and GORTEC-REACH trials investigated avelumab with chemoradiation in locally advanced HNSCC, but failed to meet their primary PFS endpoints. [19][20][21] However, the majority of patients in each study had oropharyngeal cancer, which could have masked the benefit of concurrent immunotherapy given the more favorable prognosis at this subsite.…”

Section: Toxic Effectsmentioning

confidence: 99%

A phase I/II trial of concurrent immunotherapy with chemoradiation in locally advanced larynx cancer

Frankart

Sadraei

Huth

et al. 2022

Laryngoscope Investig Oto

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Objectives Cisplatin‐based chemoradiation is an established organ‐preserving strategy for locally advanced laryngeal cancer, but long‐term survival remains suboptimal. Immunotherapy has been studied in the metastatic and unresectable recurrent settings. However, additional data are needed to assess its role in organ preservation for locally advanced laryngeal cancer. Methods This trial was an open‐label, single‐arm, multi‐institutional study with a Phase I run‐in portion followed by a planned Phase II component, which closed early due to low accrual. Study patients had Stage III or IV (T2–3; N0–3; M0) laryngeal squamous cell carcinoma and were candidates for larynx preservation. Pembrolizumab was given 2–3 weeks prior to chemoradiation and then, q21 days concurrently with high‐dose cisplatin and radiation prescribed to a total dose of 70 Gy. The primary endpoint of the trial was organ‐preservation rate (OPR) at 18 months. Results A total of nine patients were enrolled with a median follow‐up of 30.1 months. No patient required laryngectomy, resulting in 100% OPR at 18 months. The 12‐month overall survival (OS) rate was 77.8% and the median duration of OS was not reached. All acute Grade 4 (n = 3) toxicities occurred in a single patient with poorly controlled diabetes at baseline. One patient had late Grade 4 laryngeal edema requiring tracheostomy 8 months after chemoradiation, which self‐resolved. Conclusion UCCI‐HN‐15‐02 demonstrated the safety of the addition of immunotherapy to definitive chemoradiation and the patient outcomes suggest the potential for improving long‐term survival while minimizing negative impact from treatment. While results from this trial were promising, a randomized study with a larger number of patients and longer follow‐up is warranted to verify this treatment approach prior to wider adoption. NCT #: NCT02759575. Level of evidence: 2b

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LBA35 Avelumab-cetuximab-radiotherapy versus standards of care in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): Randomized phase III GORTEC-REACH trial

Abstract: Background: Based on a potential synergistic effect of antiePD-L1 avelumab plus cetuximab and radiotherapy (RT), this combination was tested in a randomized phase III trial against 2 standards of care (SOC) in LA-SCCHN.

Cited by 48 publications

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Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors

Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors

The dogma of Cetuximab and Radiotherapy in head and neck cancer – A dawn to dusk journey

A phase I/II trial of concurrent immunotherapy with chemoradiation in locally advanced larynx cancer

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