Evaluation of clinicopathological factors in PD-1 response: derivation and validation of a prediction scale for response to PD-1 monotherapy

Abstract

Background:Anti-PD-1 therapy has shown significant clinical activity in advanced melanoma. We developed and validated a clinical prediction scale for response to anti- PD-1 monotherapy.Methods:A total of 315 patients with advanced melanoma treated with pembrolizumab (2 or 10 mg kg−1 Q2W or Q3W) or nivolumab (3 mg kg−1 Q2W) at four cancer centres between 2011 to 2013 served as the setting for the present cohort study. Variables with significant association to response on a univariate analysis were entered into a forward stepwise logistic regression model and were given a score based on ORs to calculate a clinical prediction scale.Results:The developed clinical prediction scale included elevated LDH (1 point), age <65 years (1 point), female sex (1 point), history of ipilimumab treatment (2 points) and the presence of liver metastasis (2 points). The scale had an area under the receiver-operating curve (AUC) of 0.73 (95% CI 0.67, 0.80) in predicting response to therapy. The predictive performance of the score was maintained in the validation cohort (AUC 0.70 (95% CI 0.58, 0.81)) and the goodness-to-fit model demonstrated good calibration.Conclusions:Based on a large cohort of patients, we developed and validated a simple five-factor prediction scale for the clinical activity of PD-1 antibodies in advanced melanoma patients. This scale can be used to stratify patients participating in clinical trials.

Melanoma staging: Evidence‐based changes in the American Joint Committee on Cancer eighth edition cancer staging manual

“…In the seventh edition, an elevated LDH level was used to categorize a patient as M1c, regardless of anatomic site(s) of metastatic disease, given its significance as an independent, adverse predictor of survival among patients with stage IV disease. LDH remains a clinically significant factor associated with response, progression‐free survival, MSS, and overall survival in the contemporary treatment era of targeted and immune therapies . In the eighth edition, an elevated LDH level no longer independently defines M1c disease.…”

“…LDH remains a clinically significant factor associated with response, progression-free survival, MSS, and overall survival in the contemporary treatment era of targeted and immune therapies. [75][76][77] In the eighth edition, an elevated LDH level no longer independently defines M1c disease. Instead, to better codify the impact of anatomic site and LDH level, descriptors were added to the M1 subcategory designation to indicate LDH status (designated as "[0]" for not elevated and " [1]" for elevated) for each M1 subcategory ( Table 4).…”

Tissue‐specific tumor microenvironments influence responses to immunotherapies

“…A recently revealed clinical trend shows some association with liver metastases and reduced responses to αPD‐1 across cancer types in melanoma, urothelial cancer, TNBC and NSCLC . However, there are some conflicting results with some studies reporting no associations with liver metastases .…”

“…Evidence has recently emerged for the tumor location influencing the response of human tumors to immunotherapies, particularly to αPD‐1 and αPD‐1/αCTLA4 . In particular, retrospective analysis has revealed reduced responses to checkpoint blockade in tumors in certain metastatic sites compared with primary tumors in melanoma, non‐small‐cell lung cancer (NSCLC), urothelial cancer and triple‐negative breast cancer (TNBC) . Due to the complexity of tumors at different anatomical sites, including tumor genetic heterogeneity, the tissue‐specific impact on therapy responses in human tumors is yet to be elucidated.…”

Pembrolizumab in the Treatment of Metastatic Melanoma

“…[37] В общей сложности в данный анализ было включено 315 пациентов с метастатической меланомой, получавших пембролизумаб (2 или 10 мг/кг каждые 2 недели или каждые 3 недели) или ниволумаб (3 мг/кг каждые 2 недели) в четырех онкологических центрах в период с 2011 по 2013 г. Переменные, имеющие стати-стически значимую связь с ответом на лечение при одно-мерном анализе, вводили в модель пошагового логисти-ческого регрессионного анализа и получали баллы на основе относительного риска для расчета клинической шкалы прогноза (табл. 9, 10).…”