The addition of PD-1 inhibitors to induction chemotherapy produced a significant improvement in overall survival (OS) vs induction chemotherapy alone in patients with newly diagnosed locally advanced head and neck squamous cell carcinoma (HNSCC), according to data from a retrospective study published in Cancer Immunology, Immunotherapy.1
At a median follow-up of 29.23 months, after propensity score weighting was applied, patients who received PD-1 inhibitors plus induction chemotherapy experienced significantly improved OS (HR, 0.11; 95% CI, 0.03-0.37; P < .001) and progression-free survival (PFS; HR, 0.43; 95% CI, 0.20-0.89; P = .024) compared with chemotherapy alone. Moreover, patients who received PD-1 inhibitors achieved a significant improvement in best radiological responses (P = .02).
“[These findings underscore] the potential for further clinical trials to refine and optimize treatment strategies,” Yongchao Yu, of the State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, and Sun Yat-sen University Cancer Center, in Guangzhou, China, and colleagues wrote in the publication.
Locally advanced HNSCC represents approximately 60% of all diagnosed cases of HNSCC and carries a 5-year OS rate of less than 50%. Concurrent chemoradiotherapy was established as the standard of care for the treatment of patients with locally advanced HNSCC based on data from the MACH-NC meta-analysis; these findings showed that neither induction nor adjuvant chemotherapy improved survival.2
“Despite decades of research, no therapeutic strategy beyond concurrent platinum-based chemoradiotherapy has significantly improved the prognosis of [patients with] locally advanced HNSCC,” the study authors wrote.1
PD-1 Inhibitors Plus Induction Chemotherapy in First-Line Locally Advanced HNSCC
- After propensity score weighting, patients who received PD-1 inhibitors plus induction chemotherapy experienced significantly improved OS (HR, 0.11; 95% CI, 0.03-0.37; P < .001) and PFS (HR, 0.43; 95% CI, 0.20-0.89; P = .024) vs chemotherapy alone.
- The ORRs in the PD-1 and chemotherapy-alone arms were 86.1% and 76.4%; the complete response rates were 11.3% and 2.2%, respectively.
- Adding a PD-1 inhibitor to induction chemotherapy did not markedly increase the risk of severe toxicity.
How was the retrospective study designed?
The retrospective study was comprised of data from a prospectively maintained Chinese database and included patients with newly diagnosed locally advanced HNSCC who underwent induction chemotherapy between February 2012 and February 2023.1 Patients were not permitted to have received any prior treatments, including surgery, radiotherapy, or systemic therapy) prior to their first visit.
Chemotherapy regimens included platinum and taxanes, with or without 5-fluorouracil, which were given with or without PD-1 inhibitors; patients received 1 cycle of treatment every 3 weeks. Patients then received concurrent chemoradiotherapy, excluding 24 patients in the PD-1 inhibitor plus induction chemotherapy arm and 14 in the induction chemotherapy alone arm.
At baseline, the median age in the overall population (n = 204) was 57.76 years (IQR, 51.82-64.01). Most patients were male (88.7%), had stage T3/T4 disease (61.8%), had stage IV disease (84.3%), received intensity-modulated radiation therapy (89.2%), received platinum-based concomitant chemotherapy (70.1%), received 3 courses of induction therapy (58.3%), and received adjuvant therapy (84.3%). Disease sites consisted of the larynx and hypopharynx (48.0%), multisite (5.9%), oral cavity (7.4%), and oropharynx (38.7%).
The primary end point was OS. Secondary end points included PFS and overall response rate (ORR).
What were the additional findings?
In the real-world cohort, patients in the PD-1 arm (n = 115) experienced a longer OS (HR, 0.15; 95% CI, 0.06-0.38; P < .001) and PFS (HR, 0.44; 95% CI, 0.26-0.74; P = .002) in the chemotherapy-alone arm (n = 89). The ORRs in the respective arms were 86.1% and 76.4%; the complete response rates were 11.3% and 2.2%, respectively.
In terms of safety, severe adverse effects were reported in 7.8% of patients in the PD-1 cohort compared with 15.7% in the chemotherapy-only group (P = .077). No patients died due to chemotherapy in either group.
“Our findings demonstrate that the addition of PD-1 inhibitors significantly improves OS compared [with] chemotherapy alone,” Yu and colleagues wrote in their conclusion. “These results highlight the potential of PD-1 inhibitors to enhance therapeutic outcomes and support their integration into standard treatment regimens for locally advanced HNSCC.”
References
- Yu Y, Jiao Z, Wu T, et al. Comparison of induction chemotherapy with/without PD-1 inhibitors followed by concurrent chemoradiotherapy in locally advanced head and neck squamous cell carcinoma. Cancer Immunol Immunother. 2026;75(1):35. doi:10.1007/s00262-025-04284-w
- Pignon JP, Bourhis J, Domenge C, Designé L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-analysis of chemotherapy on head and neck cancer. Lancet. 2000;355(9208):949-955.
