Immunotherapy likely to become standard for recurrent/metastatic head and neck cancers
The standard treatment for patients with recurrent or metastatic head and neck cancers is expected to change from chemotherapy to immunotherapy based on results of several randomized, phase 3 studies, according to a presenter at HemOnc Today New York.
It is still unknown whether a regimen of immunotherapy and chemotherapy could become the standard of care.
“The treatment of recurrent disease in head and neck cancers is very challenging and has remained challenging even though we have made significant progress over the last few years with checkpoint inhibitors,” Robert I. Haddad, MD, chief of the division of head and neck oncology at Dana-Farber Cancer Institute, said during his presentation. “These patients have significant quality-of-life issues. They usually have a lot of pain, they can’t work, and many of them don’t socialize... so there’s a lot of reasons to look at this patient population and improve outcomes.”
Current treatment of patients with recurrent or metastatic head and neck cancers includes platinum-based chemotherapy plus the EGFR inhibitor cetuximab (Erbitux, Eli Lilly) given in six 3-week cycles. This is commonly known as the EXTREME regimen.
Cetuximab is administered at a loading dose of 400 mg/m2, followed by 250 mg/m2 weekly. The chemotherapy component includes carboplatin area under the curve (AUC) 5 or cisplatin 100 mg/m2, plus 5-FU 1,000 mg/m2 daily for 4 days.
Results of the randomized phase 3 KEYNOTE 040 trial published last year showed the anti-PD-1 therapy pembrolizumab (Keytruda, Merck) extended OS compared with standard chemotherapy for patients with recurrent or metastatic head and neck squamous cell carcinoma.
In the intention-to-treat population, pembrolizumab conferred a statistically significant OS benefit (median, 8.4 months vs. 6.9 months; HR = 0.8; 95% CI, 0.65-0.98). Researchers observed no significant PFS benefit with pembrolizumab.
The study that is expected to lead to the biggest change in care for patients with recurrent or metastatic head and neck cancers is the randomized phase 3 KEYNOTE 048 trial.
The results, published last year, showed pembrolizumab monotherapy significantly extended median OS compared with the EXTREME regimen among patients with PD-L1 combined positive score (CPS) of 20 or higher (14.9 months vs. 10.7 months; HR = 0.61; 95% CI, 0.45-0.83), as well as among patients with CPS of 1 or higher (12.3 months vs. 10.3 months; HR = 0.78; 95% CI, 0.64-0.96). In the entire cohort, OS with pembrolizumab was noninferior to that observed with EXTREME.
Objective response rates were lower among patients assigned pembrolizumab monotherapy than those assigned EXTREME (CPS 20, 23% vs. 36%; CPS 1, 19% vs. 35%; and total population, 17% vs. 36%). However, median duration of response was longer with pembrolizumab monotherapy in all three groups (CPS 20, 20.9 months vs. 4.2 months; CPS 1, 20.9 months vs. 4.5 months; and total population, 20.9 months vs. 4.5 months).
“This was a big surprise for many of us when we saw the results,” Haddad said. “What this is telling us is that using these drugs earlier increases the chances of seeing a response rate.”
In addition, pembrolizumab plus chemotherapy appeared associated with longer OS than the EXTREME regimen (13 months vs. 10.7 months; HR = 0.77; 95% CI, 0.63-0.93).
“These data are currently being reviewed by the FDA, and we expect a decision to come in the next few months,” Haddad said. “My expectation is that, over time, the EXTREME regimen will become less and less useful for us in the first-line setting.”– by John DeRosier
Haddad R. Current treatment for recurrent/metastatic disease. Presented at: HemOnc Today New York; March 21-23, 2019; New York.
Burtness B, et al. Abstract LBA8_PR. Presented at: European Society for Medical Oncology Congress; Oct. 19-23, 2018; Munich.
Cohen E, et al. The Lancet. 2018;doi: 10.1016/S0140-6736(18)31999-8.
Haddad reports consultant roles with AstraZeneca, Bristol-Myers Squibb, Eisai, Genentech, Glenmark, GlaxoSmithKline, Immunomic, Merck, Nanobiotix and Pfizer, and research funding from Bristol-Myers Squibb, Genentech, Merck and Pfizer.