Everett Vokes, MD
“PACIFIC is a positive trial, with a 32% improvement in survival, and maintenance durvalumab is a new standard of care,” stated formal discussant Everett Vokes, MD, Chair of the Department of Medicine at the University of Chicago and a pioneer in the concurrent use of chemotherapy and radiotherapy in head and neck and lung cancers. “Prior experience shows that with concurrent chemoradiotherapy, we can cure about 30% of patients. The combination is superior to chemotherapy or radiation alone. The patients enrolled in PACIFIC were carefully selected. Their disease did not progress during chemoradiation, and they were able to navigate through the challenges of that intensive therapy,” he said.
Durvalumab (Imfinzi) was shown to be safe, with grade 3 pneumonitis at 3%, which is consistent with previous reports, Dr. Vokes continued.
“This was a real-life trial,” he continued. “The chemoradiation regimen was not spelled out. Disease-specific characteristics of patients are unknown, including nodal and tumor status. The trial omitted consolidation chemotherapy. Progression-free survival was not as good as expected in controls, but survival in controls was as expected.”
Dr. Vokes continued: “There are no data on local control. The objective response rates were higher with durvalumab, which suggests that local control was improved. Distant control was improved, with lower rates of brain metastasis.”
“The fact that patients with programmed cell death ligand 1 (PD-L1) expression < 1% did not do as well in the subgroup analysis gives us pause for the future,” he noted. “This represents 150 patients of the 450 who had PD-L1 testing.” This group of patients needs further testing, and alternative strategies need to be investigated.
After second-line therapy, progression-free survival was still longer with durvalumab. “Since first progression-free survival was included in the analysis of the second progression-free survival, the analysis gave the durvalumab arm a head start. In addition, patients starting consolidation within 14 days trended better. This may reflect an apparent benefit of starting early and is important to consider in other clinical trials,” he told listeners.
Future Questions
“Maintenance durvalumab is now the standard of care and should serve as a new control arm for future trials,” Dr. Vokes concluded. “I think patients should still get PD-L1 testing, so we can learn how to treat them better. Those with PD-L1 expression < 1% may not benefit from durvalumab and may need more chemotherapy. These results also likely apply to mutation-driven tumors. We don’t know the optimal duration of therapy and need to address these questions in future trials,” he added. ■
DISCLOSURE: Dr. Vokes is a consultant/advisor to AbbVie, Amgen, AstraZeneca, Biolumina, BMS, Celgene, Eli Lilly, EMD Serono, Genentech, Merck, Novartis, and Regeneron.
