Proffered paper session on head & neck cancer

In this video, Dr Pieterjan Vanclooster discusses and comments on the data of some interesting studies presented at ESMO 2024 during the proffered paper session on head & neck cancer.

The first trial he discusses is a phase 3 clinical trial conducted in China focusing on identifying a less toxic treatment option for patients with locally advanced nasopharyngeal carcinoma (NPC), addressing the significant toxicity associated with the current standard of care. Based on a 2019 New England Journal of Medicine study, the existing regimen involves induction chemotherapy with gemcitabine and cisplatin, followed by concurrent chemoradiation with cisplatin. While this approach offers high disease control rates, many patients are unable to complete the full treatment due to its severe toxicity. The trial involved the standard of care arm (two cycles of cisplatin and gemcitabine, followed by chemoradiation with 30 mg/m² cisplatin) and an experimental arm. In the experimental arm, patients received two cycles of cisplatin and gemcitabine, followed by intensity-modulated radiation therapy (IMRT) without concurrent chemotherapy, and then another two cycles of cisplatin and gemcitabine. The primary endpoint was failure-free survival, and the trial aimed to demonstrate that the experimental regimen was not inferior to the standard treatment in terms of efficacy while reducing toxicity. The results showed that the experimental sequential treatment was non-inferior to the standard of care in controlling disease. Although the trial did not show a significant failure-free benefit, it successfully reduced mucositis, a common and severe adverse effect. However, the experimental arm was associated with higher haematological toxicity, particularly thrombopenia, which could limit the dosing and progression of treatment. One notable limitation of the trial was that the chemotherapy regimen used in the standard arm differed from that recommended in the 2019 New England study, which proposed three cycles of induction chemotherapy rather than the two cycles used in this trial. Additionally, the cumulative dose of cisplatin during the chemoradiation phase was lower than that typically used, which may have impacted the toxicity profile, particularly the reduced mucositis observed in the experimental arm. Despite these limitations, This trial sets the groundwork for further research to refine treatment protocols and integrate newer therapeutic options.

Eftilagimod alpha (efti) is a soluble Lag-3 fusion protein. Efti activates antigen-presenting cells, leading to a broad anti-cancer immune response. This includes the activation of CD8+ T-cells, stimulating both adaptive and innate immunity. When combined with PD-1 or PD-L1 antagonists like pembrolizumab, efti enhances the immune response, augmenting the effects of pembrolizumab, which antagonises the PD-1 receptor on T-cells. This combination has demonstrated encouraging efficacy in treating patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), especially after the failure of first-line chemotherapy. The TACTI-003 trial enrolled patients with HNSCC and assessed the combination of efti and pembrolizumab as a first-line treatment. In cohort A, patients with PD-L1 CPS of one or more were randomised to receive either efti plus pembrolizumab or pembrolizumab alone. In cohort B, patients with a CPS of less than one received only the combination therapy. Efti was administered as 30 mg subcutaneous injections every 2-3 weeks, and pembrolizumab was given as 400 mg intravenous infusions every six weeks. The primary endpoint was the objective response rate (ORR) by RECIST 1.1, with secondary endpoints including disease control rate (DCR) and duration of response. In cohort B, patients with CPS less than one showed an ORR of 35.5%, as reported at an ESMO virtual plenary session. In cohort A, which involved 138 patients, with 118 evaluable, the combination therapy yielded an ORR of 32.8%, rising to 34.5% after data cutoff, compared to 26.7% in the pembrolizumab-alone arm. The DCR was 72.4% in the combination arm versus 63.3% in the pembrolizumab-only arm, with a median duration of response exceeding 17 months in both groups. Among patients with a CPS of 20 or more, the ORR was 31% for the combination, compared to 18.5% for pembrolizumab alone.

Importantly, deep tumour responses were more frequent in the combination arm, particularly in patients with higher CPS scores. In contrast, unexpectedly high response rates were observed in patients with CPS scores of 1-19 treated with pembrolizumab alone, which some prognostic imbalances may explain. Regarding safety, no fatal treatment-emergent adverse reactions were reported, and there were no new safety signals. Toxicity profiles were comparable between the two groups, with grade ≥3 toxicity similarly distributed, and injection site reactions occurred only in the efti plus pembrolizumab arm.

In conclusion, the combination of eftilagimod alpha and pembrolizumab led to a numerically higher ORR than pembrolizumab alone in patients with CPS ≥1. The greatest effect was seen in patients with CPS ≥20, where the ORR was 1.7 times higher than pembrolizumab alone. The combination also maintained a favourable response duration compared to historical data from anti-PD-1 therapies with chemotherapy, suggesting a potential therapeutic advantage in this patient population.