XRT + Cetuximab = XRT alone? in locally advanced laryngeal cancer

[Gfunk6]

Published in JAMA: http://archotol.jamanetwork.com/article.aspx?articleid=2532573

I think many of us had suspected this was the case based on subset analysis of he original Bonner trial in NEJM. For larynx/hypopharynx, it seems that platinum should remain standard of care for now. If patient can't tolerate platinum it appears radiation alone may be the best second choice.

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[medgator]

Good to see additional data on the matter. Unfortunate because my experience has been that my larynx pts seem to the sickest in terms of cis tolerance vs my hpv/p16+ oropharynx pts.

 

[Burt Radnolds]

I do not interpret that as saying cetuximab + RT = RT alone for locally advanced laryngeal cancer. This is a subset analysis with small numbers, with all of the hazard ratios in favor of the addition of cetuximab with no additional toxicity. Your headline is misleading and should at minimum be followed with a ? as the question is far from answered. I definitely agree with you that cisplatin should be first choice, but would still argue that adding cetuximab is better than nothing.

 

[Gfunk6]

I do not interpret that as saying cetuximab + RT = RT alone for locally advanced laryngeal cancer.

But,

"The rates of laryngeal preservation at 2 years were 87.9% for CRT vs 85.7% for radiotherapy alone, with an HR of 0.57 (95% CI, 0.23-1.42; P = .22). Similarly, the HR for laryngectomy-free survival comparing CRT vs radiotherapy alone was 0.78 (95% CI, 0.54-1.11; P = .17). This study was not powered to assess organ preservation. Median overall survival was 27 (95% CI, 20-45) vs 21 (95% CI, 17-35) months for the CRT and radiotherapy alone groups, respectively, with an HR of 0.87 (95% CI, 0.60-1.27)."

2 year laryngeal preservation = no statistically significant difference in either arm
Laryngectomy-free survival = no statistically significant difference in either arm
Median overall survival = appears significant but overlaps with 1.0?

I see your point, will alter title.

 

[Burt Radnolds]

I totally agree, definitely not a slam dunk for cetuximab by any means. It's basically a post hoc analysis of a subgroup and all its inherent caveats. People tend to take what they want from these sorts of things. One might say, such as the authors do, that it "trends" in favor of cetuximab, which the hazard ratio and Kaplan Meier curves agree with. While on the other hand, others such as yourself will point out the lack of a single significant p value, a very legit point. In the end it doesn't give much more than a "vibe" of what cetuximab is doing in these cases. Vibes tend to be highly variable between interpreters.

 

[nkmiami]

Want to add that in the Bonner trial, 70% of patients received radiation in 6 weeks. In later subset analysis, 20 month difference in survival for patients who received 7 week course. Subset analyses are exploratory, but with such a large difference, I give 6 fractions/week with erbitux (and obviously if you are giving radiation alone.)

 

[medgator]

Want to add that in the Bonner trial, 70% of patients received radiation in 6 weeks. In later subset analysis, 20 month difference in survival for patients who received 7 week course. Subset analyses are exploratory, but with such a large difference, I give 6 fractions/week with erbitux (and obviously if you are giving radiation alone.)

A lot of us dose-paint at >2 Gy a day to the primary/involved LNs. In my clinic, 6 fractions wouldn't be feasible (can't treat BID if you are covering different linacs in the morning and afternoon).

 

[BobbyHeenan]

A lot of us dose-paint at >2 Gy a day to the primary/involved LNs. In my clinic, 6 fractions wouldn't be feasible (can't treat BID if you are covering different linacs in the morning and afternoon).

I think this is fine. I think any form of altered fractionation with cetixumab has value. Six fractions a week is what I shoot for, but if not feasible then you can go for an average weekly dose of > 10 Gy.

 

[seper]

Given that evidence for accelerated XRT is so strong now, I've switched all my H&N which are not getting chemo to 6 fractions per week (bid on Fri).

 

[medgator]

Given that evidence for accelerated XRT is so strong now, I've switched all my H&N which are not getting chemo to 6 fractions per week (bid on Fri).

Altered fractionation has been the standard of care in locally advanced h&n not getting chemo since the 4-armed RTOG study from the 90s has it not? That study showed a trend towards improved OS iirc.

 

[evilbooyaa]

But,

"The rates of laryngeal preservation at 2 years were 87.9% for CRT vs 85.7% for radiotherapy alone, with an HR of 0.57 (95% CI, 0.23-1.42; P = .22). Similarly, the HR for laryngectomy-free survival comparing CRT vs radiotherapy alone was 0.78 (95% CI, 0.54-1.11; P = .17). This study was not powered to assess organ preservation. Median overall survival was 27 (95% CI, 20-45) vs 21 (95% CI, 17-35) months for the CRT and radiotherapy alone groups, respectively, with an HR of 0.87 (95% CI, 0.60-1.27)."

2 year laryngeal preservation = no statistically significant difference in either arm
Laryngectomy-free survival = no statistically significant difference in either arm
Median overall survival = appears significant but overlaps with 1.0?

I see your point, will alter title.

Bolded the important aspect of that paragraph.

The issue is that they're reporting on something that they aren't powered to report on. Then because the HR are less than 1, and p-values are closer to 0.05 than 0.5, the authors can say its "trending towards statistical significance", insinuating that if they only had a bigger sample size (and were sufficiently powered), it's easy to see that it would totally become significant!
In short, I think the only conclusion that you can truly draw from it is that it's something to consider for future studies.

Altered fractionation has been the standard of care in locally advanced h&n not getting chemo since the 4-armed RTOG study from the 90s has it not? That study showed a trend towards improved OS iirc.

Can you point to a link or what numbered RTOG trial you're referring to?

Never mind, found it: RTOG 90-03 - https://www.ncbi.nlm.nih.gov/pubmed/10924966