Neoadjuvant IO before resection in HNSCC and implications for RT

[Palex80]

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Hey!

Our med oncs are starting to push for perioperative Pembro in resectable HNSCC based on this trial.

https://www.nejm.org/doi/full/10.1056/NEJMoa2415434

What are the implications for adjuvant RT?

The trial treated pretty much everyone with at least 60 Gy. I am wondering what am I supposed to in patients achieving major pathological response. Do I still treat the same way?

Have you seen this happening at your institutions?

 

[drowsy12]

Treat per path indications just like the trial did

The mpr and pcr rates are low. This isn’t like lung. Also there’s no chemo, which drives path responses.

 

[medgator]

Treat per path indications just like the trial did

The mpr and pcr rates are low. This isn’t like lung. Also there’s no chemo, which drives path responses.

The reps have already visited me to push for this since I refer out for the big surgeries sometimes after seeing pts from local omfs or ent's

From what I understand the trial showed decreased need for CRT vs post op RT alone given the decrease in +margins and/or +ece in the IO arm

 

[TheWallnerus]

Hey!

Our med oncs are starting to push for perioperative Pembro in resectable HNSCC based on this trial.

https://www.nejm.org/doi/full/10.1056/NEJMoa2415434

What are the implications for adjuvant RT?

The trial treated pretty much everyone with at least 60 Gy. I am wondering what am I supposed to in patients achieving major pathological response. Do I still treat the same way?

Have you seen this happening at your institutions?

What would be very cool, and trenchant, would be if we rad oncs started testing doses as low as 10 (don't laugh), 20, or 30 Gy in settings like this. We are after all already toying around with 30 Gy in head/neck cancer anyway. The great undiscovered country in rad onc HNSCC is dose de-escalation. It was predicted, kind of, long ago (Fletcher) that this was the way. Wouldn't it be interesting if A.I. could model the number of remaining clonogens to inform dosing choices after a systemic treatment since we know, as Fletcher knew, "that all epithelial tumors,such as squamous cell carcinomas, adenocarcinomas of the breast and the uterus, and mucoepidermoid, malignant-mixed, and adenoid-cystic carcinomas of the salivary glands, have approximately the same radiosensitivity, other factors being equal."

Treat per path indications just like the trial did

The mpr and pcr rates are low. This isn’t like lung. Also there’s no chemo, which drives path responses.

The degree that chemo drives path responses is very correlated to how well the immunotherapy works though (think: certain rectal cancers, especially). I remember when Eli Glatstein said to me "We are just one drug away from being out of the lymphoma game."

“Six years ago, a medical oncologist told me he had never seen a patient with HER2-positive breast cancer develop local recurrence. I set out to find patients who had recurrence in this setting. Approximately 2,000 patients later, I have not seen one, either."

 

[radonc17]

Hey!

Our med oncs are starting to push for perioperative Pembro in resectable HNSCC based on this trial.

https://www.nejm.org/doi/full/10.1056/NEJMoa2415434

What are the implications for adjuvant RT?

The trial treated pretty much everyone with at least 60 Gy. I am wondering what am I supposed to in patients achieving major pathological response. Do I still treat the same way?

Have you seen this happening at your institutions?

We are doing this per surgeon preference is they feel the upfront surgery is going to be terrible.

12% pts in trial had a delay to surgery so that's something to consider for surgeons

~20% didn't receive adjuvant therapy -> in the Pembro arm half of those were due to progression of disease

If patients made it to the adjuvant phase, they all received radiotherapy so no change in how we are treating on our end.

 

[OTN]

What would be very cool, and trenchant, would be if we rad oncs started testing doses as low as 10 (don't laugh), 20, or 30 Gy in settings like this. We are after all already toying around with 30 Gy in head/neck cancer anyway. The great undiscovered country in rad onc HNSCC is dose de-escalation. It was predicted, kind of, long ago (Fletcher) that this was the way. Wouldn't it be interesting if A.I. could model the number of remaining clonogens to inform dosing choices after a systemic treatment since we know, as Fletcher knew, "that all epithelial tumors,such as squamous cell carcinomas, adenocarcinomas of the breast and the uterus, and mucoepidermoid, malignant-mixed, and adenoid-cystic carcinomas of the salivary glands, have approximately the same radiosensitivity, other factors being equal."

View attachment 409486

The degree that chemo drives path responses is very correlated to how well the immunotherapy works though (think: certain rectal cancers, especially). I remember when Eli Glatstein said to me "We are just one drug away from being out of the lymphoma game."

“Six years ago, a medical oncologist told me he had never seen a patient with HER2-positive breast cancer develop local recurrence. I set out to find patients who had recurrence in this setting. Approximately 2,000 patients later, I have not seen one, either."

Adjuvant 30 Gy H+N trial was negative though with more recurrences compared with standard of care

 

[temujim]

Hey!

Our med oncs are starting to push for perioperative Pembro in resectable HNSCC based on this trial.

https://www.nejm.org/doi/full/10.1056/NEJMoa2415434

What are the implications for adjuvant RT?

The trial treated pretty much everyone with at least 60 Gy. I am wondering what am I supposed to in patients achieving major pathological response. Do I still treat the same way?

Have you seen this happening at your institutions?

A bit of a garbage trial. 10% of the standard of care arm noped out (vs 1% on the experimental arm) -- who knows what happened to them. The company certainly does not. And you see that in the KM curves -- essentially the entire difference occurs early -- if these patients went off and did something non-standard you might expect this result.

They received an indication for CPS >=1, but all the responses were essentially CPS >=10. If you're going to do this regimen, certainly should be restricted to this group, which was around 60% of the total.

PFS was positive, but OS was not by their own statistical testing, even in CPS >= 10. Time will tell on that. But the FDA allowing PFS endpoint to drive indications instead of OS is irritating.

The other concern is toxicity reporting -- frankly unbelievable. And there is a complete absence of surgical related toxicity reporting. Eg roughly 30% of the total population was larynx/hypopharynx and there were no permanent tracheostomies reported. But they do report radiation skin injury!

Anyway another NEJM fail.

 

[ramsesthenice]

A bit of a garbage trial. 10% of the standard of care arm noped out (vs 1% on the experimental arm) -- who knows what happened to them. The company certainly does not. And you see that in the KM curves -- essentially the entire difference occurs early -- if these patients went off and did something non-standard you might expect this result.

They received an indication for CPS >=1, but all the responses were essentially CPS >=10. If you're going to do this regimen, certainly should be restricted to this group, which was around 60% of the total.

PFS was positive, but OS was not by their own statistical testing, even in CPS >= 10. Time will tell on that. But the FDA allowing PFS endpoint to drive indications instead of OS is irritating.

The other concern is toxicity reporting -- frankly unbelievable. And there is a complete absence of surgical related toxicity reporting. Eg roughly 30% of the total population was larynx/hypopharynx and there were no permanent tracheostomies reported. But they do report radiation skin injury!

Anyway another NEJM fail.

Preopanc-2 just came out last week showing no OS for FOLFIRINOX compared to single agent gem and CRT for borderline resectable pancreatic cancer. Also reported no differences in toxicity. Of course, things like neuropathy were not presented (at least in the “it’s all good” abstract.) Was Lancet instead of NEJM, but still, they can all do better.

 

[Palex80]

Thank you, all! I was contemplating on whether or not, I can alter my radiotherapy schedule based on the pathological response.
The trial gave at least 60 Gy, ECOG-ACRIN 3311 was not published by the time they designed the trial. And we now know that we can drop the post-op dose to 50 Gy to patients in the intermediate risk group.

1. If I see major pathological response, could I drop the dose to the contralateral neck (for instance down to 30 Gy) or even ommit it completely?

2. Am I allowed to give only 50 Gy, if they are in the intermediate-risk group post-neoadjuvant Pembro as per ECOG-ACRIN-criteria?

 

[drowsy12]

3311 is for HPV positive patients. These patients are not the keynote 689 population.

follow standard dose recommendations.

 

[temujim]

Thank you, all! I was contemplating on whether or not, I can alter my radiotherapy schedule based on the pathological response.
The trial gave at least 60 Gy, ECOG-ACRIN 3311 was not published by the time they designed the trial. And we now know that we can drop the post-op dose to 50 Gy to patients in the intermediate risk group.

1. If I see major pathological response, could I drop the dose to the contralateral neck (for instance down to 30 Gy) or even ommit it completely?

2. Am I allowed to give only 50 Gy, if they are in the intermediate-risk group post-neoadjuvant Pembro as per ECOG-ACRIN-criteria?

Should emphasize that ECOG 3311 was a feasibility trial, not a non-inferiority trial. Sure things looked good, but so did HN002. Continue to believe 60 Gy is standard of care.

Elective neck I think it's reasonable to go down to 40 Gy. Still think 30 Gy is a bridge too far.