Fit elderly patients aged 70 years and older with head and neck squamous cell carcinoma (HNSCC) were able to undergo rigorous treatment that provided benefit similar to that observed in younger patients. However, elderly patients with HNSCC classified by geriatric assessment as unfit showed less benefit from systemic treatment with either cetuximab or methotrexate and those with poorer ECOG performance status (PS) derived no benefit from systemic therapy, according to findings presented at the ESMO Congress 2019 in Barcelona, Spain.
According to lead author Joel Guigay, Medical Oncology, Centre Antoine Lacassagne, Université Côte d'Azur in Nice, France the primary challenges in treating patients aged 70 years and older with HNSCC are to maximise the treatment benefit/risk ratio and manage tumour related symptoms, since no standard systemic treatment has been validated to date.
Therefore, Professor Guigay and colleagues from the GERICO-GORTEC groups developed ELAN, a large prospective clinical programme, to improve the management of elderly HNSCC patients by an adapted geriatric evaluation that is feasible for use in daily practice in order to set new standards of care for this patient population.
For inclusion into the ELAN FIT and UNFIT trials patients aged 70 years and older with recurrent or metastatic HNSCC were required to be enrolled in the ELAN-ONCOVAL study where they were classified as fit or unfit according to the ELAN geriatric evaluation (EGE) with optional Comprehensive Geriatric Assessment. Fit patients were eligible for enrolment in the 2-stage phase II ELAN-FIT trial (NCT01884623) and unfit patients could enter the randomised phase III ELAN-UNFIT trial (NCT01864772).
In ELAN FIT, 78 patients were treated with the cetuximab-carboplatin-5FU (EXTREME) combination, with a primary endpoint of efficacy evaluated as the objective response rate (ORR) 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 randomised to receive cetuximab at 500 mg/m² every 2 weeks or weekly methotrexate at 40 mg/m². The primary endpoint was failure-free survival (FFS), which was defined as disease progression, stopping treatment, death, or a loss ≥2 points in the Activities in Daily Living scale.
FIT elderly patients with HNSCC derived benefit from the EXTREME regimen
The ELAN FIT trial met the primary endpoint by demonstrating a 12-week ORR of 40% in fit elderly patients with HNSCC. Median overall survival (OS) was 14.7 months (95% confidence interval [CI], 11.0-18.1). The one-year OS rate was 58% (95% CI, 46%-68%).
Progression-free survival (PFS) with the EXTREME regimen was 7.2 months (95% CI, 5.9-8.4) and the one-year PFS rate was 24.9% (95% CI, 16.5%-35.8%).
Nearly a quarter (24%) of patients experienced a grade ≥4 adverse events (AEs).
The ELAN UNFIT trial was halted prematurely due to futility
In the ELAN UNFIT trial, the 12-week ORR was 12% in the 41 patients receiving cetuximab and 15% in the 41 patients on methotrexate. Median OS with both treatments was 4.6 months and the one-year OS 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 HNSCC median PFS was 2.4 months (95% CI, 1.5-3.8) with cetuximab versus 2.8 months (95%CI, 1.6-4.2) with methotrexate, and the one year PFS rates were 7.5% (95% CI, 2.6%-19.9%) versus 7.3% (95%CI, 2.5%-19.4%).
AEs grade ≥4 were experienced by 27% of patients on cetuximab and 22% of patients on methotrexate.
Patients with better performance status in the UNFIT trial benefited more from both treatments
When patients in both treatment arms were combined and their data were analysed according to ECOG PS, 47 patients with PS 0-1 showed improved survival compared to 35 patients with PS 2. Although the ORR at week 12 was similar in both groups (13% versus 14%, respectively) patients with PS 0-1 had prolonged median OS of 7.3 months (95% CI, 4.6-9.6) compared to 2.1 months (95% CI, 1.5-3.2) in patients with PS 2. The one-year OS rates were 27.7% (95% CI, 16.9%-41.8%) versus 5.9% (95% CI, 1.6%-19.1%) in the respective groups.
Median PFS was also longer in patients with PS 0-1 at 3.8 months (95% CI, 2.6-5.5) compared to 1.5 months (95% CI, 1.2-2.3) in patients with PS 2; the one-year PFS rate was 12.8% (95% CI, 6.0%-25.2%). No elderly unfit patients with PS 2 survived without progression for one year.
Patients with poorer performance status accounted for the majority of the serious AEs; in patients with PS 0-1 and PS 2, the respective AE grade ≥4 rates were 13% and 40%, respectively.
Patient benefit was observed in elderly patients determined as fit using EGE criteria from the carboplatin based EXTREME regimen, and promising OS was demonstrated that compared favourably with OS reported for younger patients undergoing the same treatment for HNSCC.
In elderly patients selected as unfit using the same EGE criteria, no significant efficacy difference was demonstrated between treatment with cetuximab or methotrexate. Unfit elderly patients with PS 0-1 showed some benefit with either cetuximab or methotrexate but unfit elderly patients with PS 2 did not benefit from systemic treatment. The authors suggested that new therapeutic options should be evaluated in unfit elderly patients with PS 0-1.
Funding from INCa PAIR, Merck, Sandoz, and GEMLUC-GEFLUC was disclosed.
1110O – Guigay J, Auperin A, Mertens C, et al. Personalized treatment according to geriatric assessment in 1st line recurrent and/or metastatic (R/M) Head and Neck Squamous Cell Cancer (HNSCC) patients aged 70 or over. ELAN (ELderly heAd and Neck cancer) FIT and UNFIT trials.