Fit elderly patients aged 70 years and older with head and neck squamous cell carcinoma were able to undergo rigorous treatment that provided benefit similar to that observed in younger patients. However, elderly patients with head and neck squamous cell carcinoma classified by geriatric assessment as unfit showed less benefit from systemic treatment with either cetuximab or methotrexate, and those with poorer ECOG performance status derived no benefit from systemic therapy, according to findings presented by Guigay et al at the European Society for Medical Oncology (ESMO) Congress 2019 (Abstract 1110O).
According to lead author Joel Guigay, MD, PhD, of Centre Antoine Lacassagne, Université Côte d'Azur, the primary challenges in treating patients aged 70 years and older with head and neck squamous cell carcinoma are maximizing the treatment benefit/risk ratio and managing tumor-related symptoms, since no standard systemic treatment has been validated to date.
Therefore, Dr. Guigay and colleagues developed ELAN, a large prospective clinical program to improve the management of elderly patients with head and neck squamous cell carcinoma by using an adapted geriatric evaluation that is feasible for use in daily practice in order to set new standards of care for this patient population.
ELAN Trial Program and Methods
For inclusion into the ELAN FIT and UNFIT trials, patients aged 70 years and older with recurrent or metastatic head and neck squamous cell carcinoma were required to be enrolled in the ELAN-ONCOVAL study where they were classified as fit or unfit according to the ELAN geriatric evaluation with optional comprehensive geriatric assessment. Fit patients were eligible for enrolment in the two-stage phase II ELAN-FIT trial and unfit patients could enter the randomized phase III ELAN-UNFIT trial.
In ELAN FIT, 78 patients were treated with the cetuximab/carboplatin/fluorouracil (EXTREME) combination, with a primary endpoint of efficacy evaluated as the objective response rate at 12 weeks by central review and safety assessed by grade ≥ 4 toxicity and no loss of independence.
The ELAN UNFIT study enrolled 82 patients who were randomly assigned to receive cetuximab at 500 mg/m² every 2 weeks or weekly methotrexate at 40 mg/m². The primary endpoint was failure-free survival, which was defined as disease progression, stopping treatment, death, or a loss of ≥ 2 points in the Activities in Daily Living scale.
Findings
The ELAN FIT trial met the primary endpoint by demonstrating a 12-week objective response rate of 40% in fit elderly patients with head and neck squamous cell carcinoma. Median overall survival was 14.7 months (95% confidence interval [CI] = 11.0–18.1). The 1-year overall survival rate was 58% (95% CI = 46%–68%). Progression-free survival with the EXTREME regimen was 7.2 months (95% CI = 5.9–8.4), and the 1-year progression-free survival rate was 24.9% (95% CI = 16.5%–35.8%). Nearly a quarter (24%) of patients experienced a grade ≥4 adverse events.
In the ELAN UNFIT trial, the 12-week objective response rate was 12% in the 41 patients receiving cetuximab and 15% in the 41 patients receiving methotrexate. Median overall survival with both treatments was 4.6 months, and the 1-year overall survival rates were 22.5% (95% CI = 12.3%–37.5%) with cetuximab compared to 14.6% (95% CI = 6.9%–28.4%) with methotrexate. In the elderly unfit patients with head and neck squamous cell carcinoma, median progression-free survival was 2.4 months (95% CI = 1.5–3.8) with cetuximab vs 2.8 months (95% CI = 1.6–4.2) with methotrexate, and the 1-year progression-free survival rates were 7.5% (95% CI = 2.6%–19.9%) vs 7.3% (95% CI = 2.5%–19.4%). Grade ≥ 4 adverse events were experienced by 27% of patients receiving cetuximab and 22% of patients receiving methotrexate.
When patients in both treatment arms were combined and their data were analyzed according to ECOG performance status, 47 patients with a performance status of 0 or 1 showed improved survival compared to 35 patients with a performance status of 2. Although the objective response rate at week 12 was similar in both groups (13% vs 14%, respectively), patients with a performance status of 0 or 1 had a prolonged median overall survival of 7.3 months (95% CI = 4.6–9.6) compared to 2.1 months (95% CI = 1.5–3.2) in patients with a performance score of 2. The 1-year overall survival rates were 27.7% (95% CI = 16.9%–41.8%) vs 5.9% (95% CI = 1.6%–19.1%) in the respective groups.
Median progression-free survival was also longer in patients with a performance score of 0 or 1 at 3.8 months (95% CI = 2.6–5.5) compared to 1.5 months (95% CI = 1.2–2.3) in patients with a performance score of 2; the 1-year progression-free survival rate was 12.8% (95% CI = 6.0%–25.2%). No elderly unfit patients with a performance score of 2 survived without disease progression for 1 year.
Patients with poorer performance status accounted for the majority of serious adverse events. In patients with a performance score of 0/1 and 2, the respective grade ≥ 4 adverse events rates were 13% and 40%, respectively.
Patient benefit was observed in elderly patients determined as fit using ELAN geriatric evaluation criteria from the carboplatin-based EXTREME regimen, and promising overall survival was demonstrated that compared favorably with overall survival reported for younger patients undergoing the same treatment for head and neck squamous cell carcinoma.In elderly patients selected as unfit using the same ELAN geriatric evaluation criteria, no significant efficacy difference was demonstrated between treatment with cetuximab or methotrexate.
Unfit elderly patients with a performance score of 0 or 1 showed some benefit with either cetuximab or methotrexate, but unfit elderly patients with a performance score of 2 did not benefit from systemic treatment. The authors suggested that new therapeutic options should be evaluated in unfit elderly patients with a performance score of 0 or 1.
Disclosure: Funding for the trials was provided by INCA PAIR, Merck, Sandoz, and GEMLUC-GEFLUC. For full disclosures of the study authors, visit esmo.org.
