Prospective validation of the modified metastatic colorectal cancer score ( <scp>mCCS</scp> ) in &gt;600 patients with <scp> <i>RAS</i> </scp> ‐wild‐type metastatic colorectal cancer treated with first‐line panitumumab plus <scp>FOLFIRI</scp> / <scp>

Existing prognostic scores for metastatic colorectal cancer (mCRC) are based on randomized clinical trial data and focus on parameters evaluated at the start of first-line (1L) treatment. Unlike these, the modified mCRC prognostic score (mCCS) was developed using real-world data from the German tumor registry colorectal cancer (TKK) and is based on pre-1L treatment information. It predicts overall survival (OS) for patients with RAS-wild-type (WT) mCRC using five tumor characteristics identified as independent negative prognostic factors. The mCCS aims to facilitate risk-based treatment approaches and optimize mCRC treatment. The VALIDATE study was a prospective, non-interventional study designed to validate the modified mCCS, recruiting patients with RAS-WT mCRC in Germany and Austria. A total of 646 patients from 113 study sites were enrolled in VALIDATE and received 1L therapy with panitumumab in combination with FOLFOX/FOLFIRI. Patients were categorized into risk groups according to the modified mCCS. The prognostic value of the modified mCCS was prospectively validated by demonstrating significantly longer median OS of patients in the low-risk group (29.1 months [25.9, 32.1]) compared to those in the high-risk group (20.1 months, [15.0, 23.9]). Rates of secondary resections of metastases were ≥ 23% for low and intermediate-risk patients, indicating a pivotal opportunity for improved prognosis. During panitumumab administration, patient-reported quality of life was preserved, and the tolerability profile was manageable with no new safety signals. The modified mCCS could serve as a practical tool for oncologists in routine clinical practice to aid in treatment decision-making and effectively communicating prognosis to patients.