Advertisement

Effect of Tumor Sidedness and Molecular Alterations on Outcomes in Patients With RAS/BRAF Wild-Type Metastatic Colorectal Cancer


Advertisement
Get Permission

In a study reported in the Journal of Clinical Oncology, Morano et al assessed prognostic/predictive role of tumor sidedness and presence of uncommon molecular alterations in anti-EGFR treatment primary resistance in patients with RAS/BRAF wild-type metastatic colorectal cancer.

Study Details

The prespecified retrospective analysis included 199 patients with RAS/BRAF wild-type disease who received panitumumab plus fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (FOLFOX-4) induction followed by maintenance with panitumumab with or without 5-FU/LV in the phase II Valentino trial.

Patient samples were investigated for molecular alterations using a PRESSING panel (PRESSING = primary resistance in RAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-EGFR monoclonal antibodies). The PRESSING panel included the following:

  • Immunohistochemistry (IHC) and in situ hybridization for HER2/MET amplification
  • IHC with or without RNA sequencing for ALK/ROS1/NTRKs/RET fusions
  • Next-generation sequencing for HER2/PIK3CAex.20/PTEN/AKT1 and RAS mutations with low mutant allele fraction
  • Multiplex polymerase chain reaction for microsatellite instability.

Patients were considered PRESSING-positive if they had any of the alterations, and PRESSING-negative if all were absent. PRESSING status and sidedness were correlated with overall response rate, progression-free survival, and overall survival in the study population and by treatment arm.

Outcomes by Sidedness and PRESSING Status

Overall, 85.4% of tumors were left-sided and 14.6% were right-sided. PRESSING-negative tumors were found in 75.4% of patients and PRESSING-positive tumors in 24.6%.

At a median follow-up of 26 months, poorer outcomes were observed for right- vs left-sided tumors in overall response rate (55.2% vs 74.1%; P = .037), median progression-free survival (8.4 vs 11.5 months; P = .026), and 2-year overall survival (50.2% vs 65.1%; P = .062). Poorer outcomes were also observed for PRESSING-positive vs PRESSING-negative tumors in overall response rate (59.2% vs 75.3%; P = .030), median progression-free survival (7.7 vs 12.1 months; P < .001), and 2-year overall survival (48.1% vs 68.1%; P = .021).

KEY POINTS

  • Right-sided and PRESSING-positive tumors were associated with poorer outcomes among patients receiving panitumumab plus FOLFOX-4 induction followed by maintenance with panitumumab with or without 5-FU/LV.
  • Outcomes in these tumor subgroups were particularly poor in patients receiving maintenance with panitumumab alone.

The progression-free survival benefit observed in the trial with the addition of 5-FU/LV to panitumumab maintenance was independent of tumor sidedness (P = .293 for interaction) and PRESSING status (P = .127 for interaction). Poorer outcomes were observed among patients receiving panitumumab alone as maintenance therapy who had right-sided tumors (median progression-free survival = 7.7 months, 2-year overall survival = 38.5%) or PRESSING-positive tumors (median progression-free survival = 7.4 months, 2-year overall survival = 47.0%).

The investigators concluded, “The combined assessment of sidedness and molecular alterations of anti-EGFR primary resistance identified a consistent proportion of patients with RAS/BRAF–[wild-type] [metastatic] colorectal cancer who had inferior benefit from initial anti-EGFR–based regimens, particularly after maintenance with single-agent anti-EGFRs.”

Filippo Pietrantonio, MD, of the Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, is the corresponding author for the Journal of Clinical Oncology article.

Disclosures: The study was supported by Amgen. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
Advertisement

Advertisement



Advertisement