Promising Activity Seen With Palbociclib/Cetuximab Combo in HPV-Unrelated HNSCC


An overall response rate of 39% was induced with the combination of the CDK4/6 inhibitor palbociclib and cetuximab in patients with platinum-resistant, HPV-unrelated recurrent/metastatic head and neck squamous cell carcinoma.

Douglas R. Adkins, MD

Douglas R. Adkins, MD

An overall response rate of 39% was induced with the combination of the CDK4/6 inhibitor palbociclib (Ibrance) and cetuximab (Erbitux) in patients with platinum-resistant, HPV-unrelated recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).

In findings from 1 arm of a nonrandomized, 3-arm, phase II trial (NCT02101034) presented at the 2018 ASCO Annual Meeting, the median progression-free survival (PFS) was 5.4 months (95% CI, 3.4-7.0) and the median overall survival (OS) was 9.5 months (95% CI, 5.3-16.5). The 1-year year OS rate was 35%.

“To our knowledge, the tumor response rate, the median progression-free survival, and median overall survival observed with palbociclib and cetuximab are the best efficacy data reported in patients with HPV-unrelated platinum-resistant recurrent metastatic head and neck cancer,” said lead author Douglas R. Adkins, MD, professor of Medical Oncology with Washington University School of Medicine in St. Louis.

Adkins said that the median PFS exceeds the median PFS of 70 days for patients treated with cetuximab monotherapy observed in a previous phase II study.2The median OS with palbociclib/cetuximab exceeds the median OS of 7.7 months (95% CI, 5.7-8.8) recorded for patients treated with nivolumab (Opdivo) in the CheckMate-141 trial.3

In CheckMate-141 (NCT02105636), 361 patients with cancer of the oral cavity, pharynx, or larynx were assigned to receive nivolumab (n = 240) or investigator's choice of chemotherapy (cetuximab, methotrexate, or docetaxel; n = 121). Nivolumab was administered intravenously at 3 mg/kg every 2 weeks. Cetuximab was administered at 400 mg/m2for the first dose followed by 250 mg/m2weekly. Methotrexate was administered at 40 or 60 mg/m2weekly. Docetaxel was administered at 30 or 40 mg/m2weekly.

Adkins noted that the palbociclib/cetuximab results are similar to findings from the cetuximab/chemotherapy arm of the phase III EXTREME trial for median PFS (5.4 vs 5.6 months), median OS (9.5 vs 10.1 months), and response rate (39% vs 36%).4

In EXTREME (NCT00122460), 222 treatment-naïve patients with recurrent/metastatic HNSCC were assigned to chemotherapy plus cetuximab (starting dose of 400 mg/m2, then 250 mg/m2weekly) and 220 patients received chemotherapy alone.

In the study by Adkins et al, 30 patients with HPV-unrelated HNSCC who progressed following platinum-based treatment for recurrent/metastatic disease were enrolled in the trial. Patients who previously received cetuximab for recurrent disease and those with HPV-related oropharynx cancer were not eligible.

Patients received 125 mg of daily palbociclib on days 1 to 21 plus cetuximab at a loading dose of 400 mg/m2followed by 250 mg/m2weekly in 28-day cycles until progression or withdrawal. Investigators performed imaging at baseline and after every 2 cycles.

The median patient age was 67 years (range, 26-84) and 90% (n = 27) were current or former smokers. Twenty (67%) patients had an ECOG performance status of 1, 9 (30%) had a score of 0, and 1 (3%) had a score of 2. Twenty-three men and 7 women were included in the trial.

The most common primary tumor site was the oral cavity (47%), followed by the larynx (27%) and the oropharynx (13%). Twenty percent of patients had local-regional metastases, 27% had distant metastases, and 53% had both. Fifteen (50%) patients received ≥2 prior lines of therapy.

Among 28 evaluable patients, 11 (39%) patients had a tumor response including 3 (11%) complete responses and 8 (29%) partial responses. Fourteen (50%) patients had stable disease and 3 (11%) had progression. Adkins said 70% of patients had a decrease in the sum of target lesions.

“Palbociclib and cetuximab have robust antitumor activity in platinum resistant HPV-unrelated head and neck cancer,” he added. “Targeting the biology of HPV-unrelated head and neck cancer is an effective therapeutic strategy.”

A total of 13 patients received immunotherapy, 3 before starting on trial and 10 after progression on palbociclib/cetuximab. The median PFS from the start of immunotherapy for those patients was 3.6 months and 1.9 months, respectively.

Twenty-nine patients completed a health-related quality of life survey at baseline and 22 completed the survey after 2 cycles of therapy. Investigators found that treatment with the combination did not affect quality of life.

Ten patients were alive at last follow-up and 4 remained on-study. Six patients discontinued due to progression. Twenty patients have died, 17 due to disease and 3 due to comorbidity or disease complications.

There was 1 grade 4 adverse event (AE), a thrombocytopenia, attributed to palbociclib. Grade 3 AEs attributed to palbociclib included neutropenia (n = 9), thrombocytopenia (n = 5), and anemia (n = 4). There were no grade 4 AEs attributed to cetuximab. Grade 3 AEs attributed to cetuximab included 1 case each of fatigue and an infusion reaction.

The ongoing double-blind randomized phase II PALATINUS trial is examining palbociclib plus cetuximab versus cetuximab plus placebo for the treatment of HPV-negative, cetuximab-naïve patients with recurrent/metastatic HNSCC after the failure of 1 prior platinum-containing chemotherapy regimen.


  1. Adkins D, Oppelt PJ, Ley JC, et al. Multicenter phase II trial of palbociclib, a selective cyclin dependent kinase (CDK) 4/6 inhibitor, and cetuximab in platinum-resistant HPV unrelated (-) recurrent/metastatic head and neck squamous cell carcinoma (RM HNSCC).J Clin Oncol. 36, 2018 (suppl; abstr 6008).
  2. Vermorken JB, Trigo J, Hitt R, et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy.J Clin Oncol. 2007;25(16):2171-7. doi: 10.1200/JCO.2006.06.7447.
  3. Ferris RL, Blumenschein GR, Fayette J, et al. Two-year update From CheckMate 141: outcomes with nivolumab (Nivo) vs investigator's choice (IC) in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) in the overall population and pd-l1 subgroups [published online April 17, 2018].Oral Oncol. 2018;81:45-51. doi: 10.1016/j.oraloncology.2018.04.008.
  4. Vermorken JB, Mesia R, River F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer.N Engl J Med. 2008;359(11):1116-27. doi: 10.1056/NEJMoa0802656.
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