Durvalumab Plus Chemotherapy Did Not Improve PFS Vs Cetuximab in Locoregionally Advanced Head and Neck Cancer


Results from the phase 2 NRG-HN004 trial found durvalumab plus radiotherapy did not show improved progression-free survival vs cetuximab in patients with locoregionally advanced head and neck cancer who had a contraindication to cisplatin.

Patients with locoregionally advanced head and neck cancer with a contraindication to cisplatin who received durvalumab (Imfinzi) vs cetuximab (Erbitux) in combination with radiotherapy did not have improved progression-free survival (PFS), as well as a worse incidence of locoregional failure, according to data from the phase 2 NRG-HN004 trial (NCT03258554) which was presented at the 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting.

The 2-year PFS rates were 66% in the cetuximab arm vs 51% in the durvalumab arm (HR, 1.47; 95% CI, 0.86-2.52; 1-sided P = .92). The difference was not statistically significant and did not meet the prespecified “Go/No go” decision to continue to phase 3. Moreover, the 2-year overall survival (OS) rates were 78% in the cetuximab arm vs 70% in the durvalumab arm (HR, 1.21; 95% CI, 0.63-2.31; 1-sided P = .72).

“NRG-HN004 was permanently closed and will not proceed to phase 3,” lead investigator Loren K. Mell, MD, chief of the Head and Neck Malignancy Service, vice chair of the Clinical and Translational Research, and professor of Radiation Medicine and Applied Sciences at the University of California San Diego Health, said during a presentation on the findings. “The results with cetuximab in this population were better than expected when compared with other trials, albeit the follow-up is still short. This sets a good baseline for future comparisons in future trials.”

The goal of the study was to compare the use of durvalumab vs cetuximab combined with intensity-modulated radiotherapy (IMRT) in patients who had previously been untreated. The trial’s primary end point was PFS (n = 234) and the phase 3 primary end point was OS (n = 444).

“Dominant treatment strategies for this group have included cetuximab, carboplatin and/or taxane-based chemotherapy plus radiation, or radiation alone, with conflicting data for each approach,” Mell stated. “Of these, cetuximab has been the favored control arm in other trial in cisplatin ineligible populations and is the most widely used regimen off trial, according to patterns of care studies.”

Patients were stratified by factors such as stage, and performance score/comorbidity. They were randomly assigned 2:1 to receive either durvalumab at 1500 mg every 2 weeks then every 4 weeks for 7 cycles plus 70 Gy of IMRT, or 400 mg/m2 of cetuximab at week 1 then 250 mg/m2 weekly for 8 cycles, and matched IMRT.

Patients were required to have an ECOG performance status of 2; renal impairment with creatine clearance of less than 60 cc/min, peripheral neuropathy, and hearing loss; and be 70 years or older with moderate to severe comorbidities or younger than 70 years with severe comorbidities. Patients were excluded from the trial if they had a favorable risk, p16-positive head and neck squamous cell carcinoma, a performance status of more than 2; poor organ function; and active autoimmune disease.

Of the 190 patients who were enrolled between March 2019 to July 2021, 186 were randomly assigned, 123 of whom received durvalumab and 63 received cetuximab. After the interim futility analysis, accrual was closed. The median patient age was 72 years, and 95% of patients had 3 or more comorbidities. Moreover, 84% of patients had an absolute contraindication to cisplatin. A total of 58% of patients had T3 to T4 staging, 49% had N2 to N3 disease, and 47% were p16 positive.

In patients receiving radiotherapy plus durvalumab, 87% completed IMRT at 70 Gy in the durvalumab arm vs 89% in the cetuximab arm. Seven or more cycles of cetuximab were completed in 81% of patients, 89% completed initial and concurrent durvalumab, and 61% completed all cycles of durvalumab.

Locoregional failure was statistically worse in the durvalumab arm at 32% vs 15% in the cetuximab arm (HR, 2.17; 95% CI, 1.00-4.69; 1-sided P = .04). However, distant metastases were similar with a rate of 11% in the cetuximab arm vs 9% in the durvalumab arm (HR, 0.76; 95% CI, 0.27-2.15; 2-sided P = .61).

When PFS was assessed by P16 status in the post-hoc analysis, Mell stated, “The majority of the difference in PFS occurred in the P16-negative subgroup. Outcomes are actually much better overall in both groups and similar between the 2 arms in the subset of patients who are P16 positive.”

Similar findings were reported when OS was assessed by P16 status, with the majority of differences appearing in the P16-negative population. However, when looking at locoregional failure, rates trended towards being worse in the durvalumab arm in the P16-positive subgroup.

Common grade 3 or higher toxicity in the durvalumab (69%) and cetuximab (79%) arms included dysphagia (22% vs 30%), mucositis (11% vs 20%), and dermatitis (5% vs 13%).


Mell LK, Torres-Saavedra P, Wong S, et al. Radiotherapy with durvalumab vs. cetuximab in patients with locoregionally advanced head and neck cancer and a contraindication to cisplatin: phase II results of NRG-HN004. Presented at the 2022 American Society of Radiation Oncology Annual Meeting; San Antonio, TX; October 23-26, 2022. Abstract LBA02. Accessed October 24, 2022.

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