ASCO 2023: Head and Neck Cancer Preview

While ASCO 2023 annual meeting is close, pharma giants, namely Merck Sharp and Dohme, Innovent Biologics, Shanghai Junshi Biosciences, and others, are looking at this opportunity to present their data readouts for different cancers, including Head and Neck Cancer. The 2023 ASCO Annual Meeting Program will offer presentations on the latest research in cancer care.

Competitive Landscape of HNC

The emerging pipeline for HNC patients consists of early-stage drugs as well as late-stage drugs in different lines of therapies  Potential therapies include xevinapant, pembrolizumab, toripalimab, and others. The emergence of several novel mechanisms of action like apoptosis proteins (IAP) antagonist, TIL cell therapy, and the mixture of naturally derived cytokines and chemokines in the HNC space has demonstrated a widespread potential as a combination or monotherapy regimen. Thus, the treatment landscape of HNC is expected to undergo a positive shift in the coming years. Let’s have a look the abstracts that we need to catchup with.

Head and Neck Cancer Highlights

1.     Abstract Number – LBA6002

Title: Can Sintilimab along with induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) emerge as a winner against IC-CCRT alone?

Commentary- The final abstract will be presented on the day of the presentation and would be subsequently published to the June 10, 2023 issue of Journal of Clinical Oncology.

Main Content- Patients with stage III-IVA locoregionally advanced nasopharyngeal cancer (LANPC) were included in the CONTINUUM study. Patients were randomly assigned to undergo three rounds of induction chemotherapy with gemcitabine and cisplatin, followed by cisplatin-radiation, or the same treatment with Sintilimab.

Conclusion: The effect of incorporating concurrent chemotherapy (CC) to radiotherapy (RT) following induction chemotherapy (IC) compared to IC followed by RT alone in stage II-IVB nasopharyngeal cancer (NPC) patients remains unknown in the era of intensity-modulated radiotherapy (IMRT).

2.     Abstract Number - 6009

Title – How would toripalimab fare against placebo in combination with gemcitabine and cisplatin?

Commentary- According to the final analysis of the Phase III JUPITER-02 trial, toripalimab plus gemcitabine and cisplatin demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared to chemotherapy alone as frontline therapy in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC).

Main Content- Previously, the FDA accepted for review a biologics licence application (BLA) for toripalimab in combination with gemcitabine and cisplatin for first-line treatment of patients with recurrent or metastatic NPC, as well as as monotherapy for second-line or later treatment of patients with recurrent or metastatic NPC after platinum-based chemotherapy.

Following that, Junshi Biosciences received a comprehensive response letter to its BLA for toripalimab, demanding a modification in the quality procedure.The FDA accepted a revised BLA in July 2022 based on results from the Phase II POLARIS-02 study (NCT02915432) and the Phase III JUPITER-02 trial (NCT03581786).

Conclusion: According to the company, in comparison to chemotherapy alone, a combination comprising the immune checkpoint inhibitor toripalimab certainly has the potential to bring about extraordinary improvements in the extension of life in NPC patients.

3.     Abstract Number - 6027

Title – Does the extended treatment of  xevinapant and  radiotherapy (RT) have the ability to improvise on the efficacy?

Commentary- Xevinapant is a first-in-class, oral IAP (inhibitor of apoptosis protein) inhibitor that is intended to restore cancer cell sensitivity to apoptosis produced by radiation and chemotherapy, as well as to boost antitumor immunity. It remains to be seen if the extended treatment of xevinapant along with radiotherapy can improve the efficacy.

Main Content- When compared to a vehicle control or RT alone, Xevinapant in addition to RT (Radiotherapy) enhanced antitumor effectiveness. Furthermore, RT combined with longer xevinapant dose for 4 weeks significantly increased treatment efficacy and prolonged life when compared to RT + shorter xevinapant dosing durations. In mice treated with xevinapant + RT, FACS analysis revealed patterns of increasing numbers of CD8+ T cells, natural killer cells, and dendritic cells and decreased numbers of regulatory T cells.

Extending xevinapant dose for 4 weeks after RT increased antitumor effectiveness in preclinical mice. The findings show that the impact is controlled in part by TME responses, such as increased antitumor immunity and a decreased pro-tumorigenic phenotype of CAFs.

Conclusion: Based on these findings, more research is needed to establish the mechanisms behind the therapeutic efficacy of xevinapant prolonged dosage.