Nivolumab Plus Nab-Paclitaxel Improve Responses in PD-1 Advanced HNSCC

The addition of nab-paclitaxel (Abraxane) to nivolumab (Opdivo) improved responses and survival vs historical standard therapy in patients with PD-1 inhibitor–refractory recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), according to findings from a single-arm phase 2 trial (NCT04831320) published in Cancer Medicine.¹

Efficacy data from the trial revealed among 45 evaluable patients, the objective response rate (ORR) with nab-paclitaxel and nivolumab was 46.7% (95% CI, 33.8%–59.9%; P = .0073). Four patients achieved a complete response, and 17 attained a partial response. The median duration of response (DOR) was 6.1 months (95% CI, 2.8–9.4).

Moreover, responses occurred more frequently in the HPV-positive vs HPV-negative populations, at 68.2% vs 26.1%, respectively. Additionally, those with distant metastases only experienced more frequent responses vs those with local-regional recurrence; in each group, the ORR was 68.4% vs 30.8%, respectively.

The median progression-free survival (PFS) was 5.5 months (95% CI, 3.9–7.8), and median overall survival (OS) was 13.9 months (95% CI, 9.0–18.9) after a median follow-up of 14.1 months (IQR, 7.6–20.1). Of 44 patients who discontinued the study, subsequent lines were received by 33 (75%), including 19 treated with 1 additional line and 14 treated with 2 or more additional lines of subsequent therapy.

“Among patients with PD-1 inhibitor-refractory [recurrent/metastatic] HNSCC, we conclude that nab-paclitaxel and nivolumab resulted in a higher ORR and longer median PFS than historically reported with alternative systemic therapy,” lead author Douglas R. Adkins, MD, a professor of Medicine in the Division of Oncology at Washington University School of Medicine, wrote in the publication with study coinvestigators. “These prospective data also provide important benchmarks that can be used to design future studies that test the activity of novel systemic therapy in patients with PD-1 inhibitor-refractory [recurrent/metastatic] HNSCC.”

This investigator-initiated, open-label, single-arm phase 2 study evaluated the combination of nab-paclitaxel and nivolumab among 46 patients with PD-1 inhibitor–refractory relapsed/metastatic HNSCC. Eligible participants had measurable disease per RECIST v1.1 guidelines and progression following prior PD-1 inhibitor therapy administered alone or as part of a combination regimen. Furthermore, those with an ECOG performance status of 0 or 1 and adequate marrow and organ function were permitted to enroll on the trial.

Of the 46 patients treated in the trial, 87.0% were male, with a median age of 64.3 years (IQR, 60.3-67.4). Most patients were White (91.3%), had an ECOG performance status of 0 (73.9%), and had previously smoked (63.0%). A total of 47.8% of patients had HPV-positive status, 91.3% had a PD-L1 combined positive score (CPS) of at least 1, 82.6% had received their most recent PD-1 inhibitor within 3 months prior to study enrollment, and 67.4% had prior platinum therapy for recurrent/metastatic disease. Twelve patients had experienced prior tumor responses to PD-1 inhibitor therapy.

The primary end point was ORR per RECIST v1.1 criteria. Secondary end points included DOR, PFS, OS, and adverse effects (AEs).

Among all patients on the study, 39 (84.7%) experienced grade 3 AEs, 12 (26.1%) had grade 4 AEs, and 5 (10.9%) had grade 5 AEs of any cause; there were no treatment-related deaths. The most common AEs of any grade included lymphopenia (97.8%), anemia (89.1%), hyponatremia (80.4%), leukopenia (76.1%), fatigue (67.4%), weight loss (67.4%), neutropenia (65.2%), hypoalbuminemia (63.1%), hypertension (60.9%), and peripheral sensory neuropathy (50.0%). Febrile neutropenia occurred in 1 patient (2.2%). Non-thyroid immune-related AEs occurred in 23.9% of patients, most commonly rash.

Dose modifications or treatment holds were required for 26 patients (56.5%), largely due to neutropenia and peripheral sensory neuropathy, which most frequently affected nab-paclitaxel administration.

Reference

Adkins D, Ley JC, Auberle C, et al. Nanoparticle albumin-bound paclitaxel and nivolumab for PD-1 inhibitor-refractory recurrent or metastatic head and neck squamous-cell carcinoma. Cancer Med. 2026;15(1):e71533. doi:10.1002/cam4.71533