Amgen, a multinational biopharmaceutical company discovers, develops, manufactures and delivers innovative human therapeutics, has reported results from Pegfilgrastim and Anti-VEGF Evaluation Study (PAVES), a phase III trial which evaluated Neulasta (pegfilgrastim) in 845 patients receiving Folfox or Folfiri and bevacizumab for the first-line treatment of locally-advanced or metastatic colorectal cancer. Folfox and Folfiri are two of the most commonly used chemotherapy regimens for colorectal cancer.
The study met its primary endpoint, with Neulasta significantly reducing the incidence of febrile neutropenia. Febrile neutropenia is a low white blood cell count accompanied by a fever. In the study, the incidence of grade 3 or 4 febrile neutropenia in patients receiving Neulasta across the first four cycles of chemotherapy was 2.4 per cent compared to 5.7 per cent in the placebo group (OR=0.41, p=0.014). A similar incidence of grade 3 or higher adverse events was seen in both arms of the trial (28 per cent placebo; 27 per cent Neulasta).
"This analysis showed that PAVES met its primary endpoint, with Neulasta significantly reducing the incidence of febrile neutropenia in patients with colorectal cancer," said Sean E Harper, MD, executive vice president of Research and Development at Amgen. "In addition to providing new data on Neulasta, we believe PAVES will provide valuable information to the oncology community on commonly-used chemotherapy regimens."
Follow-up results of PAVES looking at additional endpoints, including mature data on overall survival, overall response rate, time to progression and progression-free survival, will soon be presented.
The PAVES trial was multi-centre and multi-national. All patients received treatment with either Folfox or Folfiri plus bevacizumab and were randomized to one of two treatment arms that also received either placebo or 6 mg of Neulasta at least 24 hours after each cycle of chemotherapy. The primary endpoint was the incidence of grade 3 or 4 febrile neutropenia during the first four cycles. The study was not designed to define the febrile neutropenia rate of Folfox or Folfiri plus bevacizumab. Other endpoints include overall response rate, progression-free survival, overall survival, time to progression and adverse events.
One of the most common side effects of myelosuppressive chemotherapy is a low white blood cell count. An abnormally low level of neutrophils, an important infection-fighting white blood cell, is called neutropenia. The fewer neutrophils a patient has - and the longer the neutrophil count remains low - the greater the risk of developing a potentially serious infection.
Febrile neutropenia is neutropenia complicated by a fever. Fever is frequently a sign of infection and, in patients receiving myelosuppressive chemotherapy, it can sometimes be the only sign. Febrile neutropenia is a medical emergency and is associated with several potential downstream consequences.
Neulasta was approved by the US Food and Drug Administration (FDA) in 2002 to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia. Neulasta is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.