1. The 2-year progression-free survival was 50.6% in the durvalumab group vs 63.7% in the cetuximab group with HR 1.33 (non-significant).
2. Regarding safety, grade 3-4 adverse events occurred in 61% for durvalumab and 79% for cetuximab.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Concurrent radiotherapy with cisplatin is the standard treatment for locoregionally advanced head and neck squamous cell carcinoma (HNSCC), but many patients cannot tolerate cisplatin due to age, comorbidities, or toxicity concerns. While cetuximab is a commonly used alternative, its efficacy has been questioned. Immune checkpoint inhibitors, such as durvalumab, are being explored as a promising alternative. This study explored concurrent radiotherapy with cetuximab or durvalumab in advanced HNSCC for patient who are intolerant to cisplatin. The primary endpoint was progression-free survival (PFS) for phase 2 and overall survival (OS) for phase 3, and secondary endpoints included locoregional failure, distant metastasis, competing mortality, and patient-reported toxicity. 2-year PFS was 50.6% in the durvalumab group vs 63.7% in the cetuximab group with HR 1.33 (non-significant). There was no treatment effect of durvalumab across all subgroups, including p16 status and PD-L1 CPS. Median OS was not reached in the durvalumab group and not reached in the cetuximab group with an HR of 1.30 (non-significant). At 2 years, locoregional failure estimates were 31.3% for durvalumab and 18.9% for cetuximab with HR 1.71 (non-significant), distant metastasis estimates were 9.5% for durvalumab and 12.1% for cetuximab with HR 0.76 (non-significant), and competing mortality estimates were 8.6% for durvalumab and 5.3% for cetuximab with HR 1.50 (non-significant). With regards to safety, grade 3-4 adverse events occurred in 61% of durvalumab and 79% for cetuximab with the most common events being dysphagia (22% vs 30%), lymphopenia (28% vs 33%), and oral mucositis (11% vs 18%). Grade 5 adverse events occurred in 9% for durvalumab and 2% for cetuximab. The strengths of this trial included the follow-up period and methodology, and the limitations included the sample size. Overall, this trial found that adding durvalumab to radiotherapy did not improve outcomes over cetuximab with radiotherapy for cisplatin-ineligible HNSCC patients.
Click to read the study in Lancet Oncology
Click to read an accompanying editorial in Lancet Oncology
In-Depth [randomized controlled trial]: This open-label, multicenter phase 2/3 trial enrolled adults with stage III-IVB p16-negative squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or unknown HNSCC or unfavourable risk p16-positive squamous cell carcinoma of the oropharynx, with a contraindication to cisplatin (ECOG 2, creatinine clearance <60 mL/min, hearing impairment, peripheral neuropathy, or vulnerability to cisplatin. Patients were randomized (2:1) to radiotherapy with either durvalumab (n=123) or cetuximab (n=63). The median follow-up time was 2.3 years. 2-year PFS was 50.6% (95%CI, 41.5-59.8) in the durvalumab group vs 63.7% (51.3-76.1) in the cetuximab group with HR 1.33 (95%CI, 0.84-2.12, p=0.89). There was no treatment effect of durvalumab across all subgroups, including p16 status (p=0.22) and PD-L1 CPS (p=0.47 for CPS ≥1 and p=0.12 for CPS ≥20). Median OS was (95%CI, 2.9-NA) in the durvalumab group and (3.2–NA) in the cetuximab group with an HR 1.30 (95%CI, 0.74-2.28, p=0.82). At 2 years, locoregional failure estimates were 31.3% (95%CI, 23.0-40.0) for durvalumab and 18.9% (10.0-29.9) for cetuximab with HR 1.71 (95%CI, 0.89-2.38, p=0.10), distant metastasis estimates were 9.5% (95%CI, 5.0-15.7) for durvalumab and 12.1% (5.3-22.0) for cetuximab with HR 0.76 (95%CI 0.32-1.77, p=0.52), and competing mortality estimates were 8.6% (95%CI, 4.4-14.5) for durvalumab and 5.3% (1.4-13.4) for cetuximab with HR 1.50 (95%CI, 0.48-4.70, p=0.49). With regards to safety, grade 3-4 adverse events occurred in 61% of durvalumab and 79% for cetuximab with the most common events being dysphagia (22% vs 30%), lymphopenia (28% vs 33%), and oral mucositis (11% vs 18%). Grade 5 adverse events occurred in 9% for durvalumab and 2% for cetuximab. Overall, this trial found that adding durvalumab to radiotherapy did not improve outcomes over cetuximab with radiotherapy for cisplatin-ineligible HNSCC patients.
Image: PD
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