ASCO 2023: Head and neck highlights

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Published: 5 Jun 2023
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Dr Glenn Hanna - Dana-Farber Cancer Institute, Boston, USA

Dr Glenn Hanna speaks to ecancer about the key head and neck data presented at the ASCO 2023 conference.

He starts off by talking about a multicentre, open-label, randomised, controlled, phase 3 trial about concurrent chemoradiotherapy followed by adjuvant cisplatin-gemcitabine versus cisplatin-5-fluorouracil chemotherapy for N2-3 nasopharyngeal carcinoma.

The study showed that a concurrent adjuvant cisplatin-gemcitabine regimen significantly improved progression-free survival in patients with N2-3 nasopharyngeal carcinoma with acceptable toxicity.

He then discusses the dose expansion results of the bifunctional EGFR/TGFβ inhibitor BCA101 with pembrolizumab in patients with recurrent, metastatic head and neck squamous cell carcinoma.

Dr Hanna also talks about the DEPEND trial. This trial investigates neoadjuvant nivolumab, paclitaxel, and carboplatin followed by response-stratified chemoradiation in locoregionally advanced HPV-negative head and neck squamous cell carcinoma (HNSCC).

The study found that nivolumab-based neoadjuvant chemoimmunotherapy led to deep responses and response-adapted chemoradiation was associated with favourable survival and locoregional control.

 

My name is Glenn Hanna, I'm a head and neck medical oncologist at Dana Farber Cancer Institute in Boston, Massachusetts. I'm here today to highlight some of the extraordinary work of my colleagues that will show up in the oral abstract session from the head and neck cancer programme at ASCO 2023. 

I'd probably choose to highlight three abstracts in particular; they all have a little bit of a different flavour. The first one is abstract 6000. This was done at four centres in southern China and focused on a nasopharyngeal cancer population, which is endemic in that region. We've seen a wealth of trials, particularly phase III data, come from that part of the world just given how prevalent EBV associated nasopharynx cancer is. This trial was another phase III example, multicentre, and randomised patients to chemoradiation for everyone who had N stage 2-3 disease between T1-4 disease. So local regionally advanced with nodal involvement nasopharyngeal cancer. 

Those patients all got chemoradiation, but what was unique was that they randomised patients to different adjuvant regimens, one being a common regimen of gemcitabine cisplatin versus a historical regimen of platinum plus fluorouracil or 5FU. The summary of the data was really that the gem/cis outperformed the cisplatin/5FU in terms of overall survival or progression, free survival. There was a little bit of a signal towards increased toxicity, particularly cytopenias in the GC arm, just given the drugs used, but in general the the authors concluded that this regimen was probably beneficial over the PF or the cisplatin/5FU if you were going to use adjuvant therapy. 

Now the challenge interpreting this data is that there's data for neoadjuvant or upfront chemoimmunotherapy in this population that's evolving, as well as neoadjuvant chemotherapy that can be used prior to chemoradiation. So there's sort of a falling out of favour of using post-chemoradiation therapy, the idea being trying to get the therapy in upfront, the chemo or the chemoimmunotherapy, and then consolidating with chemoradiation or even, in some cases, radiation alone, as we saw in one of the other abstracts. So it's a question of how important this study was, now that we have neoadjuvant approaches in the definitive setting for nasopharynx cancer, but certainly helps us define what the adjuvant chemotherapy regimen might be. 

The second trial that I would highlight comes from the second part of the oral abstract session. This is a novel EGFR TGFβ bispecific protein called BCA101 from Bicara. This was used in combination with pembrolizumab for PD-L1 CPS 1 or greater patients within the first line with recurrent metastatic squamous cell head and neck cancer. This was an expansion cohort after the dose escalation for this head and neck population. It really showed us some interesting findings building on prior data using the EGFR antibody cetuximab with immunotherapy in head and neck. 

So this bispecific EGFR TGFβ protein with pembro showed an overall response rate approaching about 40-50%, but in particular in the HPV negative population, which arguably has some of the greatest need compared with HPV positive. The response rate was upwards of 50 plus percent, 50-56%. Tolerability was favourable with this combination: expected acneiform rash, which we see with these drugs, along with pembro, minimal bleeding events and a hint at response translating to progression free survival. 

So, it's very early just given that the expansion cohort has recently finished enrolling, but many of the responders are durable, greater than six months, and the median PFS for that HPV negative group is exceeding six months at this point. This is exciting data and may represent a combination, a chemo-free combination, with a targeted immunotherapy combination that may be able to go into the first line in a registrational confirmatory trial. 

The third and final abstract that I wanted to highlight from the meeting for head and neck was the DEPEND trial coming out of the University of Chicago. This was a really interesting chemoimmunotherapy trial using nivolumab as a PD-1 inhibitor, plus carboplatin and paclitaxel in combination for a local regionally advanced HPV negative population, which, as you know, is a group with a higher unmet need as compared with HPV positive patients. What was interesting about this trial was they were looking for a greater than 50% tumour volume reduction with the chemoimmunotherapy and those patients would then go on to a reduced dose of radiation and chemotherapy, followed by adjuvant continuation of nivolumab, versus the group with less than that volume reduction, who would get standard chemoradiation. 

While it's early findings and short follow-up with a modest number of patients, there were some interesting results. The DEPEND trial showed us that some patients with chemoimmunotherapy up-front, about half or a little more than half, actually had tumour reductions that allowed them to get the lower dose of chemoradiation followed by immunotherapy. In the early follow-up, the progression free survival and even the overall survival looked favourable in that group. So it does give us the suggestion that chemoimmunotherapy might be something we can use, based on response, to risk-stratified patients with hard to treat HPV negative disease in the curative setting. 

So these trials all have a little bit of a different flavour, a little bit of different populations. But I think for ASCO 2023 head and neck represents some of the more interesting studies that we saw come out of the meeting.