Similar Therapy Tolerance Seen Among Patients With Melanoma, Regardless of Age

Patients over the age of 65 had similar rates of serious adverse events, and nearly identical progression-free survival, when compared with younger patients.

Similar to their performance in younger patients, targeted therapies work well in older patients with BRAF-mutated metastatic melanoma (MM), according to a new study.

The report found an objective response rate (ORR) of 59% to BRAF and MEK inhibitors among patients 65 years and younger, and a 50% ORR among patients over the age of 65 (P = .6). The study was published in the journal Cancers.

Corresponding author Bernard Guillot, MD, PhD, of the University of Montpellier in France, and colleagues, noted that incidences of melanoma are rising by an estimated 3% each year—a phenomenon likely to have significant impacts on older patients since most cases of the cancer are in patients over the age of 65.

Combined BRAF and MEK inhibitors have become the recommended first-line therapy for patients with BRAF-mutated MM, but Guillot said research focusing on the efficacy or safety of such therapies in older patients is lacking.

The investigators assessed real-world outcomes of BRAF and MEK inhibitors by analyzing cases included in a French multiethnic biobank of patients with unresectable stage III or IV melanoma. Patients were included in the analysis if they had been given BRAF or MEK targeted therapy, or both, either combined or as monotherapy. A total of 353 patients were identified, all of whom had been treated between 2013 and 2017. Patients were then divided into 2 cohorts: those 65 years old or younger (n=231), and those over age 65 (n=122). The median follow-up time was 12 months, and the median time of treatment was 6.9 months.

Results showed age did not appear to be a major factor in terms of outcomes or adverse events.

Median overall survival was 20.3 months (95% confidence interval [CI], 15.5–27.9) in the younger group and 16.3 months (95% CI,14.5–26.9) in older patients (P = .8). Younger patients had a median progression-free survival of 7.8 months (95% CI, 6.4–9.9), while the older cohort had a nearly identical progression-free survival at 7.7 months (95% CI, 5.8–11.3) (P = .4).

In addition to similar ORRs reported among older and younger patients, safety outcomes were also approximately the same. Altogether, 80% of patients had at least 1 adverse event, while skin and subcutaneous, general, and gastrointestinal disorders occurred most frequently.

About one-third of adverse events (31%) were grade 3 or 4, although the rate was slightly higher in the older group (39% vs 28%, respectively).

Guillot and colleagues said their study differs from earlier clinical trials because it had a larger percentage of older patients and was based on real-world data from a multiethnic cohort, whereas clinical trials may not have been representative of the general melanoma population. However, researchers also noted it was possible adverse events were under-reported in their cohort, given the difficulty of tracking such events outside of a controlled trial setting.

The authors said that while their 1-year follow-up timeframe was sufficient to gather data on tolerance, longer studies are needed to better understand treatment efficacy and the extent to which adverse events persist.

In the meantime, Guillot and colleagues said these data are an important starting point in understanding how targeted therapies work in this cohort.

“Faced with the very limited data available in the literature, these results are essential in order to decide eligibility for TT [targeted therapy] in frail patients,” researchers concluded.

Reference:

Becquart O, Oriano B, Dalle S, et al. Tolerance and effectiveness of targeted therapies in aged patients with metastatic melanoma. Cancers (Basel). Published online June 18, 2021. doi:10.3390/cancers13123042