Study Identifies Prognostic Factors from Anti-PD-1 Therapy Use in Advanced Melanoma

Prognostic factors in advanced melanoma were identified for patients who experienced disease progression while receiving anti-PD-1, including lactate dehydrogenase, stage of disease, site of disease progression, tumor size, and mutation status, according to a study published in Cancer.

“The current study identified multiple prognostic factors in patients with advanced melanoma who developed disease progression while receiving anti-PD-1,” wrote the researchers. “Furthermore, the current study has provided additional benchmarks for the activity of existing therapies in the post-progression setting, and identified a cohort of long-term, post-progression survivors.”

A total of 247 patients experienced disease progression out of the 383 patients included in the study cohort. Median survival after disease progression was 6.8 months, with no difference in survival found after disease progression based on primary tumor subtype, receipt of prior therapy, or therapy type.

The researchers found a correlation between significantly improved survival after disease progression and clinical features at the time of progression. Specifically, the clinical features included normal lactate dehydrogenase, more favorable metastatic stage, mutation status, decreasing tumor bulk, and progression at solely existing lesions.

Approximately 54.3% of patients received additional systemic therapy after disease progression, with a total of 41 patients receiving BRAF/MEK inhibition (ORR, 58.6%, including 70.4% for BRAF/MEK-naive patients), 30 patients receiving ipilimumab (ORR, 0%), and 11 patients receiving ipilimumab plus nivolumab (ORR, 27.3%).

“Prior literature has suggested that pretreatment clinical and molecular factors such as metastatic stage, prior therapies, tumor mutational burden, and other features correlate with response and survival after anti–PD-1,” wrote the researchers. “However, to the best of our knowledge, prognostic features of survival after disease progression have not been well explored to date.”

To determine the data, the researchers evaluated a cohort of 383 consecutively treated patients receiving anti-PD-1 for advanced melanoma between 2009 and 2019. Data assessed included patient and disease characteristics at baseline and at the time of progression, subsequent therapies, objective response rate (ORR), overall survival, and progression-free survival.

As far as limitations, the study retrospective nature introduced the possibility of confounding bias. More, the number of patients treated with each treatment type was relatively small, which resulted in difficulty making sufficient comparative conclusions on treatment efficacy after disease progression.

Lastly, the study population was limited to patients with advanced melanoma treated with prior anti-PD-1, meaning it was not possible to draw conclusions regarding patients of other cancers or treatment types.

“These data will be useful for prognostication for patients and physicians, and as benchmarks for future clinical trial design,” wrote the researchers. “Prospective research is needed to define optimal treatment selection and sequencing, and molecular determinants of post-progression outcomes.”

Reference:

Patrinely Jr JR, Baker LX, Davis EJ, et al. Outcomes After Progression of Disease With Anti-PD-1/PD-L1 Therapy for Patients With Advanced Melanoma. Cancer. DOI: 10.1002/cncr.32984.