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Integrating the Latest Evidence for Immunotherapy into Community Care for Locally Advanced Head and Neck Cancer: Best Practices for the Multidisciplinary Team

Major Breakthroughs for Immunotherapy in HNSCC

Why Immunotherapy in HNSCC?

Dr. Haddad: Okay, great. Let us start about why immunotherapy in head and neck squamous cell carcinoma. We know that head and neck cancer is an immunogenic disease with immune evasion within the TME.

We know that the PD1/PD‑L1 axis is a key mechanism for T cell suppression. We have obviously two types of head and neck cancer.

We think of head and neck cancer in 2026 as two different diseases. One is HPV‑related, and one is tobacco/alcohol related. These may have immune relevance and how we treat these patients.

There is a significant biomarker complexity in head and neck cancer. The one that we use often in clinic to determine treatment is CPS, which is a reflection of PD‑L1 status. That is obviously based on the above strong biological rationale why checkpoint blockade is indicated in this disease.

As many of you know, both pembrolizumab and nivolumab are currently approved and indicated in head and neck cancer patients.

[00:10:20]

CheckMate 141: Nivolumab vs Investigator’s Choice in Platinum‑Refractory R/M HNSCC

One of the first phase III studies to show benefit of a checkpoint inhibitor in head and neck cancer is shown here. That is the CheckMate 141, which was a phase III trial, where we essentially looked at the activity of nivolumab versus investigator's choice in patients who have progressed on platinum‑based therapy. This is recurrent metastatic disease.

This is a positive trial that showed that nivolumab was superior to the investigator's choice chemotherapy; 7.7 months for nivolumab and investigator's choice chemotherapy was 5.1 months.

This study led to the FDA approval of nivolumab in patients with platinum‑refractory head and neck cancer.

[00:11:04]

KEYNOTE‑040: Pembrolizumab vs SoC in Platinum‑Refractory R/M HNSCC

KEYNOTE‑040 was also a phase III study that had a similar design comparing pembrolizumab to standard of care chemotherapy.

The overall survival in this trial also favored pembrolizumab, and this also supported pembrolizumab just like nivolumab as a valid alternative in the post‑platinum era.

[00:11:28]

KEYNOTE‑048: Pembrolizumab ± Chemotherapy vs EXTREME in R/M HNSCC

These two studies obviously occurred before the landmark study, which is the KEYNOTE‑048 study shown here. This is a very important trial that is changed the standard of care for the first‑line, recurrent metastatic head and neck cancer patients. This is a trial where three arms were compared.

Arm one is pembrolizumab only. Arm two is pembrolizumab + chemotherapy using a platinum 5‑FU platform, followed by pembrolizumab maintenance. The third arm is what is known as the EXTREME regimen, which is cetuximab with platinum 5‑FU.

This is 882 patients. This trial enrolled patients in the first line ‑ and this is important ‑ first‑line recurrent metastatic disease. Think of your patients who had chemoradiation, and then subsequently has lung metastasis, liver metastasis, or even local recurrence. Those are the patients that were enrolled on this trial.

[00:12:25]

KEYNOTE‑048: OS for Pembrolizumab Alone vs Cetuximab/Chemotherapy

This was a positive trial favoring pembrolizumab and pembrolizumab/chemotherapy over the EXTREME regimen. When you look at the first curve to the left here in the CPS≥1, the pembrolizumab arm was better than the cetuximab chemotherapy arm. The OS was 12.3 versus 10.4. You see the hazard ratio and the p‑value there.

For the CPS≥20, the benefit was even greater. Those patients appear to benefit the most when the CPS is 20 or more; 14.9 months versus 10.8. You see to the EXTREME right the total population, 11.5 versus 10.7.

This is the comparison of pembrolizumab alone versus chemotherapy/cetuximab.

[00:13:08]

KEYNOTE‑048: OS for Pembrolizumab/Chemotherapy vs Cetuximab/Chemotherapy

When you look at the pembrolizumab + chemotherapy versus cetuximab/chemotherapy, you will see similar trends. CPS≥1 and CPS≥20 and the total population, all of these favor the pembrolizumab/chemotherapy over cetuximab/chemotherapy.

This trial, the KEYNOTE‑048, established pembrolizumab or pembrolizumab/chemotherapy as the standard of care for head and neck cancer patients in the first‑line recurrent metastatic setting.

[00:13:34]

KEYNOTE‑048 5‑Yr Follow‑up: OS Across Treatment Arms

Looking at the five‑year follow‑up of this trial, which was published in the European Journal of Cancer, again the benefit is maintained. On top, you see the pembrolizumab arm, on the bottom, you see pembrolizumab + chemotherapy arm. Consistently benefit of the pembrolizumab over the non‑pembrolizumab containing arm at the five‑year mark.

[00:13:56]

Evidence for Predictive Value of PD‑L1 CPS

This is an important slide because it really shows you the data for the CPS<1. For those patients, you should not be using pembrolizumab alone. As you can see, for the CPS<1, the cetuximab/chemotherapy arm actually performs better; 11.3 months versus 7.9 months. This is why, obviously, it is important to get a CPS score on your patients, because you do not want to give someone with a CPS‑0 pembrolizumab alone. That would be inappropriate treatment.

For the CPS 1‑19, you see that the pembrolizumab arm is 10.8 months, similar to the cetuximab/chemotherapy arm.

With the pembrolizumab/chemotherapy, you could give pembrolizumab/chemotherapy, you see the numbers there, 11.3 months or 10.7. My recommendation here is that if you have a CPS‑0 patient, your options are either pembrolizumab + chemotherapy or cetuximab/chemotherapy. If your CPS is zero, you should not be giving pembrolizumab as a single agent.

[00:15:01]

Evidence for Predictive Value of HPV

When we look at the HPV value here ‑ and this has been looked at in a number of trials ‑ the one to the left is a trial where we examined the benefit of nivolumab/ipilimumab in this disease.

When you look at the p16 status, this is a study where we compared nivolumab + ipilimumab over EXTREME. CheckMate‑651 was a negative study. It did not reach the primary endpoint of improving overall survival, but it was very helpful in identifying subgroups of patients where there was benefit. For example, if you look at the CPS 20 or more, you see the benefit of nivolumab/ipilimumab of 17.6 months, which is numerically superior to the EXTREME regimen. When you look at the p16 status, oropharyngeal patients, p16‑positive. Remember, those patients do very well as compared to the p16‑negative, but there is no difference in these numbers between nivolumab, ipilimumab, and EXTREME in this large phase III trial.

[00:15:56]

Clinical Implications of KEYNOTE‑048

The clinical implications of KEYNOTE‑048 are listed here, trying to give you a sense of where you give pembrolizumab/chemotherapy or where you give pembrolizumab monotherapy.

One thing to remember, if you are CPS‑0, you should not be giving pembrolizumab monotherapy. Pembrolizumab monotherapy is best suited for patients who have a higher CPS, especially those patients with a CPS of 20 or more.

Also, it is important to use this option when the disease is not rapidly progressive or symptomatic. It has a lower response rate than chemotherapy/immunotherapy, but those responses, remember, can be durable. Obviously, the toxicity is lower when you are not using chemotherapy.

For the pembrolizumab + chemotherapy, I do prefer that regimen when I have a sense that the patient has rapid progression or high disease burden, where I am looking for a quick response to trying to make the patient feel better.

That indication has broader eligibility, regardless of CPS, because, as I showed you, even with CPS‑0, you could use the pembrolizumab/chemotherapy arm, and it obviously will have a higher toxicity because you are giving pembrolizumab/platinum/5‑FU when you combine pembrolizumab chemotherapy.

The right regimen essentially depends on the CPS, disease burden, symptoms, and urgency of response needed for these patients.

[00:17:18]

Systemic Therapy Recommendations for Non‑nasopharyngeal HNSCC*

This is a summary of how the NCCN guidelines look for first‑line. For other circumstances, you can consider multiple options and agents. For the first line, obviously, pembrolizumab alone or pembrolizumab + chemotherapy is really the preferred regimen based on the KEYNOTE‑048 study.

[00:17:38]

Posttest 1

Let us go back to answer the first question we started with.

A 65‑year‑old male who was treated initially for the p16‑positive oropharyngeal squamous cell carcinoma, has a complete response, but now has more than 20 bilateral lung nodules with a NavDX and a positive biopsy.

How would you treat this patient? These are your five choices:

A. Cetuximab + platinum + 5‑FU

B. Pembrolizumab

C. Pembrolizumab + platinum + 5‑FU

D. Nivolumab + ipilimumab

E. Dostarlimab

Speaker: Poll is open. Five more seconds. All right. Thank you. We will close the poll and share the results.

Dr. Haddad: Most of you used the pembrolizumab + platinum + 5‑FU. This would be the most correct answer here. There are two correct answers here: pembrolizumab is a correct answer, and pembrolizumab + chemotherapy is also a correct answer.

[00:18:51]

Rationale

I would pick pembrolizumab + chemotherapy, which is what the majority of you have picked, primarily because this patient has significant disease burden. He has more than 20 bilateral lung nodules. I would worry about this patient giving him pembrolizumab alone. However, pembrolizumab alone is not a wrong answer because the CPS is nine, so it is more than one. It is reasonable to start with pembrolizumab and then add chemotherapy later if that is what you choose, especially if the patient is completely asymptomatic. My preference would be what is listed here, and most of you have chosen, the pembrolizumab + chemotherapy.

[00:19:29]

What Is the Next Logical Population with HNSCC to Place Immunotherapy, Given Its Current Success in the R/M Setting?

Let us talk now about the locally advanced setting, which is really a setting that has undergone massive change in 2025, where the standard of care has now changed.

[00:19:38]

NIVOPOSTOP: Adjuvant Nivolumab + SoC for Locally Advanced HNSCC

This is what is known as the NIVOPOSTOP trial. This is an adjuvant trial where patients with resectable head and neck cancer... This is now the curative setting we are talking about. These are patients with resectable head and neck cancer, primarily oral cavity, who had surgery first, and they had high‑risk features on final pathology, positive margin, extranodal extension, multiple nodes.

They were randomized to either chemotherapy + radiotherapy, which is the standard of care, or chemotherapy + radiotherapy with nivolumab, followed by maintenance nivolumab, with the primary endpoint of disease‑free survival.

[00:20:12]

NIVOPOSTOP: Disease‑Free Survival (ITT)

This was a positive study initially presented at ASCO, and subsequently published in full manuscript in The Lancet this year. The primary endpoint of disease‑free survival is shown here.

There was benefit in the DFS with the nivolumab/chemotherapy RT as compared to chemotherapy/radiotherapy with a hazard ratio of 0.76.

The benefit of nivolumab in this trial appears to be primarily on locoregional control and not on distant metastatic disease, which is the impact we saw in the KEYNOTE‑689, where the benefit was primarily on distant metastatic disease. The overall survival data is not yet mature.

This is a positive trial. It has not yet been incorporated in national guidelines. It is not clear whether this is a registration trial for nivolumab, but a positive trial in this disease.

[00:21:07]

NIVOPOSTOP: Common TRAEs

These are the toxicities noted that are mostly expected when you combine chemotherapy/radiation with a checkpoint inhibitor.

[00:21:16]

KEYNOTE‑689: Perioperative Pembrolizumab + SoC for Locally Advanced HNSCC

The other study that also is a passive study that has caused a significant change in the standard of care for head and neck cancer patients, is a study that we were involved in called the KEYNOTE‑689. This has led to FDA approval. It is now a standard of care for oral cavity or resectable head and neck cancer patients.

In this trial, we took patients with resectable head and neck cancer and randomized them to either upfront surgery, which is the standard of care, or two doses of pembrolizumab before surgery.

After surgery, patients were treated based on the final pathology. If they had high‑risk features, they were treated with cisplatin, radiation, and pembrolizumab, and if they had low‑risk features, they were treated with radiation and pembrolizumab.

Essentially, this is what is called a perioperative phase III trial, where pembrolizumab was introduced before surgery. This is a major difference between this trial and the one I showed you before, where patients had surgery first before they had a checkpoint inhibitor.

[00:22:18]

KEYNOTE‑689: EFS (Primary Endpoint) in All Participants

This was a positive trial. Again, led to FDA approval. The primary endpoint event‑free survival in all participants is shown here with a hazard ratio of 0.73 and a p‑value of 0.008.

[00:22:33]

KEYNOTE‑689: EFS in CPS‑10 Population

This is the CPS‑10 data, also positive EFS.

[00:22:37]

KEYNOTE‑689: EFS in CPS‑1 Population

This is the CPS‑1 population, which is where the FDA approval is. This is indicated for patients with CPS‑1 or more in the United States. This is the hazard ratio. Significant difference with using pembrolizumab before surgery for two cycles, three weeks apart.

[00:22:56]

NIVOPOSTOP vs KEYNOTE‑689

This summary is important in summarizing the differences between these two trials. Both of these trials enrolled primarily oral cavity patients, but the major difference is that the KEYNOTE‑689 trial is a perioperative trial, where the checkpoint inhibitor was introduced before surgery, where NIVOPOSTOP was selected for patients with high‑risk disease, positive margin, extranodal extension, and the checkpoint inhibitor was introduced after surgery.

The benefit of NIVOPOSTOP was locoregional control. The benefit in the KEYNOTE‑689 was distant metastatic control, raising the question whether introducing that checkpoint inhibitor early on does serve as an insight to vaccination or an immune priming that allows those immune cells to remain in the system throughout the course of the treatment and thus decreasing the rate of distant metastatic disease.

[00:23:52]

Posttest 2

In patients with locally advanced head and neck cancer, for which population was there a PFS benefit with adding perioperative pembrolizumab to surgery and chemotherapy/ RT? These are your four choices.

A. Patients with PD‑L1 CPS ≥20 only

B. Patients with PD‑L1 CPS ≥10 only

C. Patients with PD‑L1 CPS ≥1 only

D. All patients regardless of PD‑L1 CPS level

Speaker: Poll is open. Five more seconds. All right. Thank you. We will close the poll and share the results.

[00:24:46]

Rationale

Dr. Haddad: The FDA label is CPS‑1 or more, but the study showed benefit regardless of PD‑L1 CPS. Remember, the vast majority of patients on this trial had a CPS‑1 or more. Those of you who answered CPS‑1 or more are thinking of the FDA label, which is the correct label for this trial. However, as I showed you in one of the slides before, all patients, regardless of their CPS level, showed benefit on this trial.

[00:25:20]

Given the Success of Immunotherapy in HNSCC, Would It Be a Logical Treatment for NPC?

Nasopharyngeal Carcinoma

Let us talk about nasopharyngeal carcinoma briefly here, where we are also not currently using checkpoint inhibition as a standard of care for recurrent metastatic disease.

Remember, NPC is very common in some parts of Asia, Africa, Brazil, Eastern Europe. Not very common in the U.S., but common enough. We probably see one or two cases per month at the Dana‑Farber.

There are biological basis to use immunotherapy for NPC. They are listed here.

[00:25:51]

Phase II POLARIS‑02: Toripalimab in Previously Treated R/M NPC

The first study that showed immunotherapy works in this disease is with a drug called toripalimab. This is the POLARIS‑02 study, which was a single‑arm study of toripalimab, which is a PD1 inhibitor and the first PD1 inhibitor to be approved in the U.S. for nasopharyngeal carcinoma. The study showed a significant activity of this agent as a single agent in nasopharyngeal carcinoma, and even higher benefit seen in those patients with a high PD‑L1 expression.

[00:26:23]

JUPITER 02: 1L Toripalimab + Gemcitabine/Cisplatin for R/M NPC

The registration trial for this agent in the U.S. and worldwide is shown here, the JUPITER study. First line recurrent metastatic NPC, looking at the addition of toripalimab to the standard of care gemcitabine/cisplatin.

This is a randomized phase III trial comparing placebo gemcitabine/cisplatin given every three weeks versus toripalimab + gemcitabine/cisplatin given every three weeks with a maintenance toripalimab for the primary endpoint of progression‑free survival.

[00:26:52]

JUPITER‑02: PFS

This was a positive trial, again leading to FDA approval and also worldwide approval and adaptation of this regimen for metastatic NPC patients.

You see the benefit here of toripalimab + chemotherapy, 21 months PFS versus eight months with chemotherapy + placebo. Very significant difference in favor of toripalimab + chemotherapy. That is the current standard of care for recurrent metastatic NPC patients.

[00:27:19]

Additional Phase III Clinical Trials in 1L R/M NPC

These are the two other studies that also show that adding PD1 inhibition to gemcitabine/cisplatin improved PFS. One is called RATIONALE‑309 with a drug called tislelizumab, and the other one is called CAPTAIN‑1ST with camrelizumab + gemcitabine/cisplatin. A large number of trials essentially showing that adding a PD1 inhibitor to chemotherapy improves outcome in the progression‑free survival in patients with recurrent metastatic NPC. However, toripalimab is the one currently indicated in the U.S. for these patients.

[00:27:52]

AK105‑304: 1L Penpulimab + Chemotherapy for R/M NPC

This agent was also approved last year in the U.S. for the same indication. It is called penpulimab. Similar design, penpulimab + chemotherapy versus placebo/chemotherapy.

[00:28:04]

AK105‑304: PFS by BICR (Primary Endpoint)

This was also a positive trial leading to FDA approval in this indication of first‑line recurrent metastatic nasopharyngeal carcinoma in the U.S.

[00:28:16]

Systemic Therapy Recommendations for Nasopharyngeal Cancers

This is adapted from NCCN guidelines, where we essentially put in the preferred regimen to be toripalimab + cisplatin/gemcitabine for these patients with recurrent metastatic nasopharyngeal carcinoma.

[00:28:33]

Food for Thought

Now, as you will probably see, over the next decade, you are going to start seeing those agents move to the first‑line curative setting of NPC.

Here, what I show you are a number of trials; CONTINUUM, BEACON, DIPPER, where these are, I would call them the initial attempts to bring the checkpoint inhibition to the curative setting, meaning in combination with induction chemotherapy, gemcitabine/cisplatin, or as an adjuvant after radiation chemotherapy.

These are not considered to be standard of care approaches in 2026, but I show them here just for completion. To give you a sense that these agents are moving to the first‑line curable setting, as we call induction chemotherapy. We know that they work in recurrent metastatic. Now, a lot of work is going into moving these agents to the upfront curative setting before chemotherapy radiation as an adjuvant or neoadjuvant intervention.

[00:29:32]

Review Patient Case

We go back to the case we showed before. A 49‑year‑old male who has metastatic NPC that is Epstein‑Barr positive, where the patient has lung metastases.

[00:29:43]

Posttest 3

How would you treat this patient? These are the five options presented to you.

A. Cisplatin + gemcitabine x 3 followed by cisplatin concurrent with radiation

B. Cisplatin + 5‑FU

C. Cisplatin + gemcitabine

D. Cisplatin + gemcitabine + toripalimab

E. PD‑1 inhibitor monotherapy

Speaker: The poll is open. Five more seconds. All right. Thank you. We will close the poll and share the results.

[00:30:30]

Rationale

Dr. Haddad: Most of you picked the correct answer here, which is really cisplatin + gemcitabine + toripalimab. As I showed you, for recurrent metastatic NPC, the addition of toripalimab to chemotherapy improves outcome. For this patient with lung metastases, my answer would be toripalimab + cisplatin + gemcitabine, which is what the majority of you have chosen.

[00:31:03]

Emerging Agents in HNSCC

Emerging Agents in Clinical Trials

In terms of emerging agents and head and neck cancer, what is coming over the next 5 to 10 years? What I show you here really are what I consider the most promising agents. We have seen really very impressive data with the EGFR inhibitor, what I call the new generation bispecific antibodies with EGFR inhibitors.

The first one is petosemtamab. Petosemtamab is an EGFR/LGR5 antibody that is currently in two phase III trials. One is first line in combination with pembrolizumab, and the second one is versus investigator choice.

The other agent is the ficerafusp alfa, which is another EGFR/TGF‑β antibody. It is also in phase III study. These two agents, petosemtamab and ficerafusp, have shown impressive phase II data and are both currently in phase III.

The other agent that is in the newcomer is amivantamab, which has also shown impressive phase II data that I am going to show you next. This has currently moved into phase III trial in that first‑line recurrent metastatic setting in a study called the OrigAMI‑5.

The other agent shown on top here is essentially a radiation sensitizer called NBTXR3, which is also in phase III study that is ongoing.

[00:32:25]

OrigAMI‑4: Amivantamab in R/M HNSCC

This is the amivantamab data. Amivantamab data comes from what is known as the OrigAMI‑4 trial, which is a multicohort trial looking at amivantamab as a single agent or with pembrolizumab or with chemotherapy.

[00:32:40]

OrigAMI‑4: Tumor Response

The first presentation we saw from Kevin Harrington in Berlin last year is shown here, which is amivantamab as a single agent in the HPV‑negative patient population, showing an impressive response of 76% in a patient population that is already been exposed to a checkpoint inhibitor and to platinum.

Really, a significant single‑agent activity of amivantamab, which is a drug that probably many of you are using for your lung cancer patients. This agent is now moving into the head and neck space in a subcutaneous formulation that appears to be much better tolerated than the IV formulation you might be using for your lung cancer patients.

[00:33:22]

irAE Management in HNSCC

Toxicities With Chemotherapy, Targeted Therapy, and Immunotherapy in HNSCC

Let us talk a little bit about toxicity of these agents. We have immunotherapy, which I am sure many of you are familiar with: pneumonitis, hepatitis, colitis, dermatitis, endocrine toxicity.

Obviously, with chemotherapy, the traditional side effects of nausea, vomiting, bone marrow suppression.

With cetuximab, primarily skin rash and acneiform rash, nail disorders. Very common with cetuximab.

This is really more of a summary slide of what do we expect with the checkpoint inhibitors with chemotherapy or with cetuximab.

[00:33:57]

PD‑1 Inhibitor Time to Onset and Time to Resolution of irAEs Based on Melanoma Data

The timing of the checkpoint inhibitor toxicity might allow you to really recognize those toxicities and manage them effectively. You see, for example, on the left side, the differential time frames for toxicities between skin toxicity, GI toxicity, endocrine toxicity like hypothyroidism is very common with checkpoint inhibitors. It is not usually an indication to stop the treatment. Is fairly easy to treat hypothyroidism with thyroid replacement therapy, for example.

Obviously, these are common toxicities with these agents that we as medical oncologists are very familiar with and can manage effectively in this day and age.

[00:34:46]

Immune Checkpoint Blockade: Patient Assessments

Obviously, prior to each dose of a checkpoint inhibitor, clinical assessment of the immune‑related adverse events, getting appropriate blood work as shown here, imaging every 8 to 12 weeks to decide on whether you continue with the same treatment or whether you need to change your treatment.

[00:35:05]

General Guidelines for Managing Immune‑Related AEs

The grading is important because it allows you to decide whether you will stop the treatment. If you have a grade 4, obviously, recommendation is to permanently discontinue treatment, or if you have a grade one where you could continue the treatment, but observe the patient more closely.

[00:35:22]

Immune‑Mediated Endocrinopathies: Symptom Management

Thyroid dysfunction, as mentioned, is very common. You could consider getting an endocrine input if you have access to that. If it is only a thyroid dysfunction, you can initiate thyroid replacement therapy, which is quite effective. If it is a hypophysitis, I think endocrine consultation becomes more important for those patients, and initiating hormone replacement therapy that might be required indefinitely for some of these patients.

[00:35:49]

Endocrine irAEs

Again, this is listing the endocrine‑immune‑related adverse event. Remember also for our patients that radiation can be a cause of hypothyroidism. It is important to follow the TSH levels closely on our patients because there are many reasons why they could be hypothyroid.

[00:36:08]

Management of Grade 3/4 Immune‑Related Colitis

Grade 3/4 immune related colitis are listed here. If it is a grade 3 in combination therapy, discontinue. Grade 4, permanently discontinue immunotherapy for these patients. They might need admission to the hospital, supportive care, getting GI involved for evaluation, all part of the day‑to‑day management of severe colitis in this day and age.

[00:36:32]

Biopsy‑Proven Pneumonitis Is Highly Variable in Presentation

Pneumonitis can be variable and can present in many shapes and forms. These are some X‑rays of an immune‑related pneumonitis that you might encounter in your practice.

[00:36:45]

Management of Immune‑Mediated Pneumonitis

Some recommendations of how you could manage pneumonitis in this patient population. For some, you will need to hold the treatment, treat the patient, but you can rechallenge if it is a grade 2 toxicity, for example. If it is a high‑grade toxicity, you might need to discontinue treatment, get pulmonary involved for bronchoscopy biopsy, initiate appropriate therapy for these patients that could include monoclonal antibodies or antibiotics.

[00:37:15]

Final Polling

Posttest 4

The final question that we asked you today is, which approach would you recommend for a patient who develops grade 2 pneumonitis while on an immune checkpoint inhibitor? These are the four options presented to you.

A. Continue therapy and treat with steroids

B. Hold therapy, treat with steroids, and then rechallenge at full dose

C. Hold therapy, treat with steroids, and then rechallenge at a reduced dose

D. Permanently discontinue therapy

Speaker: Poll is open. Five more seconds. All right. Thank you. We will close the poll and share the results.

[00:38:03]

Rationale

Dr. Haddad: Most of you have decided to rechallenge... For this patient, you could rechallenge at a full dose after you treat with steroids being a grade two. I think there is some variation where people would reduce the dose. It is not clear that for a grade two, you need to do that. You could rechallenge the patient at the full dose if it is a grade 2 toxicity that is treated with steroids.

[00:38:33]

Poll 4

The final question we have ‑ and I am leaving some time for questions. Hopefully, we get some questions from the audience.

Do you plan to make any changes to your practice based on today's program? These are your answers.

A. Yes

B. No

C. Uncertain

Speaker: Poll is open. Five more seconds. All right. Thank you. We will close the poll and share the results.

Dr. Haddad: Okay. Many of you are going to change their practice, and we have some that are uncertain. Thank you.

[00:39:28]

Poll 5

This is a QR code where you can text some of your responses on the changes you are planning to make in your clinical practice. Would appreciate any feedback that could help us as we design future CME programs.

Speaker: Once again, you can scan the QR code on the screen, or we do have a polling box open where you can simply type in your answer. Once again, Dr. Haddad, we will leave the polling box open. You can go ahead and move forward.

[00:40:00]

Question & Answer Session

Speaker: At this time, we are taking any questions you may have for Dr. Haddad. Please use the Q&A function in Zoom to submit them.

[00:40:09]

Thank You for Attending!

While you do so, we will put the two QR codes back on the screen momentarily. There are also links in the chat panel. One will lead to the downloadable slide deck from today's presentation, so you have that as a resource moving forward. The other is for the program evaluation link to complete to claim your credit for attending today. You will need to log in to or sign up for a DCE account in order to access this information. We would encourage you to claim your credit within 30 days, as credit for today's program will expire after this time frame.

Again, please enter any questions you may have in the Q&A feature. Dr. Haddad, I do see there are a few that have come through already. Are you able to see those, sir? I can read them to you as well.

Dr. Haddad: Yes, please, I do not know why I cannot see them.

Speaker: Okay, I have got it right here.

Would you still favor chemo‑IO in a CPS‑9 patient with low disease burden?

Dr. Haddad: If it is a low disease burden, I would probably start with immunotherapy alone. With pembrolizumab alone, and then assess after two months of treatment. If the patient is responding, stay on pembrolizumab because obviously you will gain on the toxicity if you did that. My answer would be, start with pembrolizumab alone in a CPS‑9 patient and low disease burden.

The question we had showed you that is why I said you could actually use pembrolizumab alone in that patient. However, for that patient, I would consider them to have a high disease burden. That is why we picked pembrolizumab plus chemo. This is a very good question, really, that for a low disease burden CPS‑9, I will start with pembrolizumab alone, not with pembrolizumab/chemotherapy.

Speaker: Great. Thank you, sir. The next question is, when do you repeat or question a CPS result?

Dr. Haddad: That is really a good question. Depending on the tissue availability. If you happen to have someone with metastatic disease and you had biopsy of the metastatic disease, then I would use that test. I would test the most recent biopsy on the patient. If you happen to have a situation where the patient was treated, let us say nine months ago, for locally advanced disease, and all you have is their initial biopsy, you could rely on that patient's initial biopsy CPS to initiate treatment.

One thing I would tell you is that, in head and neck cancer, CPS‑0 is not common; it is actually quite rare. The literature suggests 15 to 20%. My personal experience is that the number is much lower than that. If you have someone with CPS‑0 and you are not convinced that that number is accurate, you could consider repeating the CPS through another tissue. To me, the answer to that question really depends on the availability of tissue. If you have a situation where you have more than one tissue available, I would test the most recent one and go with that result to initiate therapy. If you only have one tissue biopsy available, which is the initial diagnostic tissue, you could test it for CPS and go with that test and initiate treatment for patients.

Speaker: All right. Thank you so much. One final opportunity for any questions for Dr. Haddad. Please go ahead and enter those in the Q&A section if you have any further questions.

Okay. There is a comment in the chat function. Are you able to see that, Dr. Haddad?

Dr. Haddad: I see something about cemiplimab. "I am a patient to start this in two days." I am not sure. That is not a question. Cemiplimab is not approved in the U.S. for head and neck cancer; it is approved for skin cancer. It is a very active agent in skin cancer. I am not sure what the... Seems like a comment about cemiplimab. Appropriate agent for cutaneous malignancies; it is not a drug we use in head and neck cancer.

Any other questions here or comments? Unless you are seeing something, I am not.

Speaker: There is one more question that just came in. It says, "Other than pneumonitis, what are the side effects of the new immunotherapy?"

Dr. Haddad: All the checkpoint inhibitors have a similar toxicity profile: colitis, hepatitis, pneumonitis, and thyroid dysfunction. In head and neck cancer, the only immunotherapy agents approved currently are the checkpoint inhibitors. As many of you know, all the other agents we have tested, like the LAG‑3, the TIM‑3, those agents actually do not show significant activity in this disease. All the trials presented to date have been negative.

The only immunotherapy agents approved in head and neck cancer today, 2026, in the U.S. are the PD1 inhibitors. We have three of them. We have nivolumab and ipilimumab in head and neck cancer, and then we have toripalimab in nasopharynx. All of these have a similar toxicity profile that we showed in the slide deck: pneumonitis, hepatitis, and colitis. Any organ can get inflamed with these agents. Those are the ones we see in the clinic. Unfortunately, all the other ones have not shown activity in this disease. All the trials so far have been negative. Only PD1 inhibitors are approved and available in the U.S. today in 2026.