Two treatment regimens have shown promise for treating elderly or frail patients with head and neck squamous cell carcinoma (HNSCC), according to researchers.
One regimen — the nanoparticle NBTXR3 followed by radiotherapy — demonstrated efficacy and tolerability in elderly or frail patients with locally advanced HNSCC in a phase 1 trial.1
The other regimen — paclitaxel, carboplatin, and cetuximab (PCC) — was deemed safe and effective for elderly or frail patients with previously untreated, metastatic, or recurrent HNSCC based on results of a retrospective study.2
Both studies were presented at the 2021 American Society of Clinical Oncology Annual Meeting.
Nanoparticle Plus Radiotherapy
NBTXR3 is a novel radioenhancer composed of functionalized hafnium oxide nanoparticles that is injected once intratumorally and activated by radiotherapy.
The phase 1 study of NBTXR3 (ClinicalTrials.gov Identifier: NCT01946867) enrolled patients with locally advanced HNSCC (stage III-IVA or T3/T4) who were ineligible for cisplatin or cetuximab.
The patients received a single intratumoral injection of NBTXR3, followed by 70 Gy of intensity-modulated radiotherapy (2 Gy in 35 fractions over a 7-week period).
There were 19 patients enrolled in the dose-escalation portion of the study, which established the recommended phase 2 dose of NBTXR3 as 22% of baseline tumor volume.3
The dose-expansion cohort included 52 patients.1 They had a median age of 71.6 years (range, 44.5-89.9 years), 71.2% were men, 53.8% had tumors of the oropharynx, and 46.2% had tumors of the oral cavity. Most patients had stage IVA (40.4%) or stage III (38.5%) disease, and 57.1% were HPV-negative.
The median follow-up was 8.1 months. All 52 patients were evaluable for safety, and they all experienced adverse events (AEs). Grade 3/4 AEs were reported in 20% of patients.
There were 6 serious AEs related to NBTXR3 observed in 5 patients — swollen tongue, tumor hemorrhage, stomatitis, soft tissue necrosis, dysphagia, and sepsis. All of these AEs but the swollen tongue were also related to radiotherapy.
Of the 10 deaths due to AEs, 3 were related to radiotherapy alone, 1 was related to radiotherapy and disease, and 1 was possibly related to NBTXR3, radiotherapy, and disease.
There were 40 patients evaluable for efficacy. The objective response rate (ORR) was 82.5%, and the complete response rate was 62.5%. Survival results are pending.
“These results are consistent with those observed in the dose-escalation part of the study and suggest durable efficacy,” said Jared Weiss, MD, associate professor of medicine at the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, who was not involved in the study.
“This nanoparticle along with radiotherapy also appears to work with immunotherapy. If large studies confirm the results seen thus far, this is a winner. It looks like the mechanism of action is broadly applicable,” Dr Weiss added.
A global phase 3 trial (ClinicalTrials.gov Identifier: NCT04892173), which is expected to launch this year, will test NBTXR3 plus radiotherapy, with or without cetuximab, in elderly patients who are ineligible for cisplatin.
Researchers evaluated PCC in a retrospective, observational study based on data from electronic medical records.2
The study included 80 adults who received PCC for HNSCC from 2014 to 2019, including 22 patients who received PCC as induction and 58 who were treated for metastatic or recurrent disease.
The patients’ median age at treatment was 62 years (range, 33-84 years), and 81% were men. About half of patients (49%) had stage IVA disease, 13% had stage IVB, and 25% had stage IVC. This was a predominantly HPV-negative population, with 16% of patients being p16 positive.
Elderly and frail patients (age ≥75 years, performance status ≥2, and albumin <3.5 g/dL) were analyzed as a subset in addition to the overall group. Elderly/frail patients comprised 39% of the total group, 50% of the induction group, and 34% of the metastatic or recurrent group.
In the metastatic or recurrent disease group, the mean overall survival (OS) was 15.2 months, the mean progression-free survival (PFS) was 7.1 months, and the ORR was 22%. In the elderly/frail subset of this group, the mean OS was 10.9 months, the mean PFS was 4.6 months, and the ORR was 15%.
In the induction group, the mean OS was 29.8 months, the induction success rate was 86%, and the ORR was 64%. In the elderly/frail subset, the mean OS was 30.6 months, the induction success rate was 82%, and the ORR was 73%.
About half of patients (52%) experienced at least 1 grade 3 or higher AE. Toxicities prompted dose interruptions in 67% of patients and treatment discontinuation in 14%.
The most common AEs were hematologic (76%), dermatologic (71%), and gastrointestinal (62%).
“[P]CC is effective and less toxic than standard of care for metastatic and recurrent head and neck cancer and is particularly effective for induction chemotherapy as well, especially in the elderly and frail population in our predominantly HPV-negative cohort,” said investigator Rebecca Forman, MD, an internal medicine resident at the Yale School of Medicine in New Haven, Connecticut.
“Future directions for research would include additional options for this important subset of patients and continuing to examine the tolerance of our chemotherapies for this subset of elderly and frail populations.”
Disclosures: The NBTXR3 study was supported by Nanobiotix. Dr Weiss disclosed relationships with Nanobiotix and other companies. No funding was reported for the PCC study, and Dr Forman reported having no conflicts of interest. Please see the original references for a full list of disclosures.
- Le Tourneau C, Calugaru V, Takacsi-Nagy Z, et al. Phase I study of functionalized hafnium oxide nanoparticles (NBTXR3) activated by radiotherapy in cisplatin-ineligible locally advanced HNSCC patients. J Clin Oncol. 2021;39:(suppl 15; abstr 6051). doi:10.1200/JCO.2021.39.15_suppl.6051
- Forman R, Bhatia AK, Burtness B, et al. Efficacy and toxicity of weekly paclitaxel, carboplatin, and cetuximab as induction chemotherapy or in cases of metastases or relapse for head and neck cancer in elderly or frail patients. J Clin Oncol. 2021;39:(suppl 15; abstr 6042). doi:10.1200/JCO.2021.39.15_suppl.6042
- Hoffmann C, Calugaru V, Borcoman E, et al. Phase I dose-escalation study of NBTXR3 activated by intensity-modulated radiation therapy in elderly patients with locally advanced squamous cell carcinoma of the oral cavity or oropharynx. Eur J Cancer. 2021;146:135-144. doi:10.1016/j.ejca.2021.01.007