Daily highlight in head and neck cancer

Reported by Dr Michael Saerens, University hospital, Ghent

In the ADJORL1 study, the efficacy and safety of nivolumab were investigated as adjuvant therapy in patients with Head and Neck Squamous Cell Carcinoma (HNSCC) following salvage surgery. All participants in this trial had previously undergone radiation therapy and surgery, either for a primary tumour or relapse. The two-year Disease-Free Survival (DFS) and Overall Survival (OS) rates were 47% and 68% respectively, surpassing outcomes observed in earlier cohorts undergoing reirradiation therapy. CTLA-4 and PD-L1 expression levels proved valuable as predictive biomarkers for DFS and OS. Further investigations are warranted to assess the viability of adjuvant therapy versus a perioperative approach involving neoadjuvant and adjuvant strategies. Additionally, understanding patient categorization based on factors such as PD-L1 status requires further exploration.

Previous trials, namely KEYNOTE412 and JAVELIN 100, demonstrated that simultaneous administration of checkpoint inhibitors with chemoradiation (CRT) did not enhance survival in patients with locally advanced HNSCC. Subsequent research examined whether sequential or concurrent administration would be a more rational approach to improve outcomes. Pembrolizumab was administered either post-CRT completion or concurrently, both for 24 weeks. At the four-year follow-up, patients in the sequential arm exhibited numerically superior Progression-Free Survival (PFS) and OS, although statistical significance was not achieved. Notably, sequential administration induced significant alterations in the tumour microenvironment, suggesting that concurrent administration of checkpoint inhibitors might promote immunosuppressive activity and radiation resistance, leading to less favourable patient outcomes.

In the SAKK 11/16 trial, a novel compound, MVX-ONCO-1, was evaluated in relapsed/metastatic HNSCC patients following one year of systemic therapy. Cell encapsulation technology was employed to create personalized vaccines with controlled release of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) and autologous tumour cells. In this phase 2 study, the primary endpoint was OS at 26 weeks. With a median OS of 11.4 months, the results were promising. One- and two-year OS rates were 49% and 30% respectively. Positive response rates were observed, and the compound demonstrated a favourable safety profile, with localized adverse effects such as itching and redness. This approach appears to be a promising and safe treatment for heavily pretreated relapsed/metastatic patients.

The TROPiCS-03 trial investigated the role of sacituzumab govitecan (SG) in relapsed/metastatic HNSCC patients. This compound, previously used in breast cancer therapy, was explored in head and neck cancer due to reports suggesting overexpression of Trop-2 in a substantial percentage of patients (60% to 80%). Heavily pretreated patients received intravenous SG treatment on day 1 and day 8 of a three-week cycle. The primary endpoint, Overall Response Rate (ORR), was achieved in only 16% of patients, indicating a disappointing outcome. Immediate Duration of Response (DOR) was approximately 4 months, and around 58% of patients experienced grade 3-5 toxicity, which was merely managed through dose reductions. These findings underscore the necessity for improved patient selection criteria to identify individuals who would benefit from this treatment.

In relapsed/metastatic HNSCC patients, mutations in the HRAS gene (mHRAS) are rare but can be targeted with farnesyltransferase inhibitors such as tipifarnib. Screening about 5000 patients revealed mHRAS in 3.4% of cases. Subsequent treatment with oral tipifarnib at a dose of 600mg twice daily on a 7-day on/off cycle in 59 patients resulted in a 30% ORR. Despite the small subset of HNSCC patients and the limited study cohort, these results are promising and highlight the potential of farnesyltransferase inhibitors.

References:

Even C. – Adjuvant immunotherapy after salvage surgery in head and neck cancer squamous cell carcinoma (HNSCC): phase 2 trial evaluating the efficacy and the toxicity of Nivolumab (ADJORL1). ESMO2023 – 855MO

Zandberg D. – A Randomized Phase II Study of Concurrent vs. Sequential Pembrolizumab with Chemoradiation (CRT) in Locally Advanced Head and Neck Cancer (LA HNSCC): 4-year results and tumor-immune microenvironment analysis. ESMO2023 – 856MO

Mach N. – SAKK 11/16, a phase IIa trial evaluating overall survival (OS) for recurrent/metastatic Head & Neck Squamous Cell Carcinoma (RMHNSCC) patients (pts) progressing after ≥ 1 line of systemic therapy, treated with MVX-ONCO-1, a novel, first in class cell encapsulation-based immunotherapy. ESMO2023 – LBA46

Michel L. – Sacituzumab govitecan (SG) in patients (pts) with relapsed/refractory (R/R) advanced head and neck squamous cell carcinoma (HNSCC): Results from the phase 2 TROPiCS-03 basket trial. ESMO2023 – 859MO

Han F. – MRG003, a novel EGFR-targeted antibody-drug conjugant (ADC) for recurrent/metastatic Nasopharyngeal Carcinoma. ESMO2023 – 860MO

Ho A. – A phase 2 study evaluating tipifarnib in mHRAS, recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) (AIM-HN study). ESMO2023 – LBA47