Details

Autor(en) / Beteiligte

• Redman, Jason M
• Tsai, Yo-Ting
• Weinberg, Benjamin A
• Donahue, Renee N
• Gandhy, Shruti
• Gatti-Mays, Margaret E
• Abdul Sater, Houssein
• Bilusic, Marijo
• Cordes, Lisa M
• Steinberg, Seth M
• Marte, Jennifer L
• Jochems, Caroline
• Kim, Sunnie S
• Marshall, John L
• McMahon, Sheri
• Redmond, Erica
• Schlom, Jeffrey
• Gulley, James L
• Strauss, Julius

Titel

A Randomized Phase II Trial of mFOLFOX6 + Bevacizumab Alone or with AdCEA Vaccine + Avelumab Immunotherapy for Untreated Metastatic Colorectal Cancer

Ist Teil von

• The oncologist (Dayton, Ohio), 2022-03, Vol.27 (3), p.198-209

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• FOLFOX plus bevacizumab is a standard of care (SOC) for first-line treatment of microsatellite-stable metastatic colorectal cancer (MSS mCRC). This study randomized patients to SOC or SOC plus avelumab (anti-PD-L1) plus CEA-targeted vaccine. Patients with untreated MSS mCRC enrolled to a lead-in arm assessing safety of SOC + immuno-oncology agents (IO). Next, patients were randomized to SOC or SOC + IO. The primary endpoint was progression-free survival (PFS). Multiple immune parameters were analyzed. Six patients enrolled to safety lead-in, 10 randomized to SOC, and 10 to SOC + IO. There was no difference in median PFS comparing SOC versus SOC + IO (8.8 months (95% CI: 3.3-17.0 months) versus 10.1 months (95% CI: 3.6-16.1 months), respectively; hazard ratio 1.061 [P = .91; 95% CI: 0.380-2.966]). The objective response rate was 50% in both arms. Of patients analyzed, most (8/11) who received SOC + IO developed multifunctional CD4+/CD8+ T-cell responses to cascade antigens MUC1 and/or brachyury, compared to 1/8 who received SOC alone (P = .020). We detected post-treatment changes in immune parameters that were distinct to the SOC and SOC + IO treatment arms. Accrual closed after an unplanned analysis predicted a low likelihood of meeting the primary endpoint. SOC + IO generated multifunctional MUC1- and brachyury-specific CD4+/CD8+ T cells despite concurrent chemotherapy. Although a tumor-directed immune response is necessary for T-cell-mediated antitumor activity, it was not sufficient to improve PFS. Adding agents that increase the number and function of effector cells may be required for clinical benefit.