Oxaliplatin-based chemotherapy with a regimen such as FOLFOX with or without targeted therapy is a standard of care option for advanced colorectal cancer; however, long-term exposure to oxaliplatin is associated with cumulative toxicity. Growing evidence suggests maintenance therapy with a less intensive regimen after platinum-based induction therapy can provide continuing benefit with reduced toxicity. We describe the rationale and design of the Phase III LYNK-003 trial, which will evaluate the efficacy and safety of olaparib with or without bevacizumab compared with 5-fluoruracil plus bevacizumab in patients with unresectable or metastatic colorectal cancer that has not progressed on an induction course of FOLFOX plus bevacizumab. The primary end point is progression-free survival by independent central review; secondary end points include overall survival, objective response, duration of response and safety. Clinical trial registration: NCT04456699.
Keywords: 5-fluorouracil; FOLFOX; PARP inhibitor; bevacizumab; colorectal cancer; folinic acid; irinotecan; maintenance therapy; olaparib; oxaliplatin.
Lay abstract Commonly used treatments for patients with advanced colorectal cancer are intensive chemotherapy-based combinations. However, long-term treatment with chemotherapy can cause significant toxic effects. To overcome this problem, patients with colorectal cancer are treated with chemotherapy for a short time, followed by a less aggressive maintenance regimen of the chemotherapy drug 5-fluorouracil and the targeted therapy drug bevacizumab. Here, we describe the rationale and design of the LYNK-003 study, which will investigate whether targeted therapy with olaparib alone or olaparib with bevacizumab compared with 5-fluorouracil and bevacizumab is effective and safe in patients with advanced colorectal cancer. Drugs like olaparib or bevacizumab specifically target proteins that promote cancer cell proliferation and have fewer toxic effects than chemotherapy. The results of LYNK-003 may lead to the availability of new chemotherapy-free maintenance options for patients with advanced colorectal cancer.