Robert Ferris, MD, PhD, vice chair for Clinical Operations, associate director for Translational Research, and co-leader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute, discusses the latest data in head and neck cancer presented at the 2019 ASCO Annual Meeting.
Although PD-1 inhibitors have been tested in the second-line setting, they had yet to show a survival benefit in the frontline setting—until the phase III KEYNOTE-048 trial, says Ferris. In the trial, patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma and PD-L1—positive tumors experienced a 22% reduction in the risk of disease progression or death with pembrolizumab (Keytruda) monotherapy versus the standard EXTREME regimen, which comprises cetuximab (Erbitux) with carboplatin or cisplatin plus fluorouracil (FU; HR, 0.78; 95% CI, 0.64-0.96; P = .0171). In the overall population, the combination of the PD-1 inhibitor and chemotherapy led to a 23% reduction in the risk of disease progression or death (HR, 0.77; 95% CI, 0.63-0.93; P = .0067). On June 11, the FDA approved pembrolizumab monotherapy for patients with a composite positive score ≥1 or in combination with platinum and FU, irrespective of PD-L1 expression. Patients who are in need of a faster response may be better suited to receive the combination of pembrolizumab and chemotherapy, adds Ferris.
In the same theme of moving immunotherapy earlier in the treatment journey, Ferris was part of the phase II RTOG 3504 trial, which investigated the addition of nivolumab (Opdivo) to chemoradiotherapy in patients with intermediate- or high-risk locoregionally advanced head and neck cancer. This is a patient population with relatively poor survival. By adding immunotherapy to standard cisplatin and chemoradiotherapy, investigators illustrated the safety and efficacy of the approach. Data from the phase III JAVELIN Head and Neck 100 trial are also eagerly anticipated; if positive, these data may lead to the incorporation of immunotherapy into the locally advanced setting.
Beyond the progress that has been made with immunotherapy, targeted therapy is also an area of interest in the field. Also presented at the meeting were data from the phase III NRG-RTOG 1016 trial, which compared the use of cetuximab and radiation with cisplatin and radiation. Here, investigators sought to determine the optimal backbone of therapy for patients with HPV-positive oropharyngeal squamous cell carcinoma. Although cetuximab failed to meet the noninferiority criteria for overall survival in the overall population, it performed as well as cisplatin in very fit patients with a performance status of 0, says Ferris. Cetuximab has proven to be a safe backbone upon which to add immunooncology drugs, but it remains to be seen whether cetuximab is a better combination partner than chemotherapy.
Cetuximab is actively being explored with other agents, adds Ferris, one of which is the PARP inhibitor palbociclib (Ibrance). The hope is that this approach may lead to tumor suppression as well as stimulation of the immune system, concludes Ferris.