immunotherapy cheat sheet for radonc tumor boards [crowdsourcing] [sticky?]

[bevacizzlemab]

You:
“ChatGPT, please write me a cheat sheet of key immunotherapy trials I should be aware of as a radiation oncologist in 2024, grouped by disease site. Include PubMed or journal URLs. Exclude distantly metastatic trials.
-be me
-be MD
-at tumor board”

ChatGPT 4.0:
As an AI language model, I do not have pre-authorization to assist you in medical decision making. Please consult your Insurance Medical Director for next best steps in managing your patient. You may file an appeal requesting that your insurer reconsider its decision to deny your claim within 180 days in writing or by phone if urgent.



Immunotherapy (non-metastatic) radonc cheat sheet
- emphasis on practice changing trials & important negative studies
- please reply to this thread with suggested additions


CNS

(negative) RTOG 0825 newly dx glioblastoma: bevacizumab vs placebo, with/after SOC chemoRT (https://www.nejm.org/doi/full/10.1056/NEJMoa1308573)

Bevacizumab in recurrent glioma (2018 Cochrane review: Anti-angiogenic therapy for high-grade glioma - PubMed)


H&N

(negative) JAVELIN Head and Neck 100: avelumab (anti-PD-L1) vs placebo, with SOC chemoRT for locally advanced H&N squamous cell Ca (https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30737-3/abstract)


BREAST

HERA (NEJM 2005): 1-yr trastuzumab vs observation, after SOC locoregional therapy + adjuvant chemotherapy in breast cancer HER2-positive, node-negative or node-positive (https://www.nejm.org/doi/full/10.1056/NEJMoa052306)

KATHERINE (NEJM 2019): Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and cytotoxic emtansine (DM1) microtubule inhibitor in patients w/ HER2-positive early breast cancer with residual invasive disease in breast or axilla at surgery after receiving neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab. (https://www.nejm.org/doi/full/10.1056/NEJMoa1814017, Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer - PubMed)

KEYNOTE 756 (SABCS 2023) pembro vs placebo, added to SOC neoadjuvant chemotherapy and adjuvant endocrine therapy in breast cancer high-risk, ER+/HER2-negative, grade 3, T1c-T2 with 1-2 +LN or T3-T4 with 0-2 +LN (Neoadjuvant Chemoimmunotherapy Improves Pathologic Complete Response Rates in Subgroup Analysis of KEYNOTE-756 - The ASCO Post)

CheckMate 7FL (ESMO 2023) nivolumab vs placebo, with SOC neoadjuvant chemotherapy & adjuvant endocrine therapy in breast cancer high risk, ER+/HER2-negative, grade 2 (ER 1–‍10%) or 3 (ER ≥ 1%), T1c-T2 N1–N2 or T3–T4 N0–N2
(ESMO Congress 2023 | OncologyPRO)


LUNG

PACIFIC: consolidative durvalumab vs placebo, after SOC chemoRT in NSCLC III (Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer - PubMed)

CheckMate 816: neoadj chemoimmunotherapy (nivolumab + platinum-based chemo) vs neoadj chemo alone, then resection in NSCLC IB to IIIA (https://www.nejm.org/doi/full/10.1056/NEJMoa2202170)

Phase 2 “I-SABR”: +/- concurrent/adjuvant nivolumab x4c q4wk, with SOC SABR/SBRT for NSCLC IA IB IIA IIB or isolated parenchymal recurrences (Stereotactic ablative radiotherapy with or without immunotherapy for early-stage or isolated lung parenchymal recurrent node-negative non-small-cell lung cancer: an open-label, randomised, phase 2 trial - PubMed)

(negative) PACIFIC-2: concurrent durvalumab vs placebo, with SOC chemoRT in unresectable NSCLC III (ClinicalTrials.gov)


LYMPHOMA

2002: DLBCL R-CHOP vs CHOP (https://www.nejm.org/doi/full/10.1056/NEJMoa011795)


UPPER GI

CheckMate 577: +/- adjuvant nivolumab to SOC neoadjuvant chemoRT + R0 resection in esophageal/GEJ cancer II or III (https://www.nejm.org/doi/full/10.1056/NEJMoa2032125)


LOWER GI

Single agent dostarlimab (anti-PD-1 mAb) for dMMR rectal adenocarcinoma stage II or III (PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer - PubMed)

(negative) NSABP C-08 and AVANT trials: adding bevacizumab to FOLFOX for high risk colon Ca stage II or III (https://ascopubs.org/doi/10.1200/JCO.2010.32.2701)


GYN

RUBY: dostarlimab vs placebo q6wk up to 3-yr, with/after SOC chemo (carbo/Taxol q3wk x6c) in endometrial cancer advanced stage III or IV or first recurrent (includes dMMR-MSI-H patients) - Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer - PubMed

KEYNOTE 826: 1st-line pembrolizumab vs placebo, + SOC chemotherapy (with or without bevacizumab) for Persistent, Recurrent, or Metastatic Cervical Cancer (First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826 - PubMed, Pembrolizumab or Placebo Plus Chemotherapy With or Without Bevacizumab for Persistent, Recurrent, or Metastatic Cervical Cancer: Subgroup Analyses From the KEYNOTE-826 Randomized Clinical Trial - PubMed)

KEYNOTE A18: pembrolizumab vs placebo, with/after SOC chemoRT + brachy boost in cervix Ca treatment-naïve, stage IB2 to IIB node+, or stage III to IVA node+ or node-negative (Pembrolizumab/Chemoradiotherapy Shows Clinically Meaningful PFS Improvement in Cervical Cancer)


PROSTATE
Checkmate ??? (tinyurl.com/utreatnodes)


BLADDER

CheckMate 274: adjuvant nivolumab vs placebo up to 1-yr, after SOC radical surgery for muscle-invasive bladder/urothelial carcinoma. Neoadjuvant cisplatin-based chemotherapy allowed before trial entry. (https://www.nejm.org/doi/full/10.1056/NEJMoa2034442)


SKIN

KEYNOTE-716: adjuvant Pembrolizumab versus placebo, after complete resection of melanoma IIB or IIC (Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial - PubMed)

Phase 2 - Neoadjuvant cemiplimab prior to resection of cutaneous squamous cell carcinoma stage II, III, or IV (M0) - Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma - PubMed

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[Neuronix]

You:
“ChatGPT, please write me a cheat sheet of key immunotherapy trials I should be aware of as a radiation oncologist in 2024, grouped by disease site. Include PubMed or journal URLs. Exclude distantly metastatic trials.
-be me
-be MD
-at tumor board”

ChatGPT 4.0:
As an AI language model, I do not have pre-authorization to assist you in medical decision making. Please consult your Insurance Medical Director for next best steps in managing your patient. You may file an appeal requesting that your insurer reconsider its decision to deny your claim within 180 days in writing or by phone if urgent.



Immunotherapy (non-metastatic) radonc cheat sheet
- emphasis on practice changing trials & important negative studies
- please reply to this thread with suggested additions


CNS

(negative) RTOG 0825 newly dx glioblastoma: bevacizumab vs placebo, with/after SOC chemoRT (https://www.nejm.org/doi/full/10.1056/NEJMoa1308573)

Bevacizumab in recurrent glioma (2018 Cochrane review: Anti-angiogenic therapy for high-grade glioma - PubMed)

Is bevacizumab immunotherapy? I guess everything that ends in mab is immunotherapy now.

Also, that's how I manage all my patients: consulting my insurance medical director for best steps.

 

[medgator]

Did it miss the stage III/IV localized cervix ca study with adjuvant keytruda? Just came out though earlier in 2024

https://www.reuters.com/business/healthcare-pharmaceuticals/mercks-keytruda-combo-gets-fda-nod-expanded-use-cervical-cancer-2024-01-12/

 

[elementaryschooleconomics]

Whoa whoa whoa

We're getting a little ahead of ourselves

I would start with:

"Dear ChatGPT, how do I, the Radiation Oncologist, get listened to at Tumor Board?"

 

[TheWallnerus]

https://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-improved-pfs-in-stage-iii-lung-cancer.html

 

[bevacizzlemab]

Have you ever been dunked on hard by medoncs at tumor board, blindsided by the latest immunotherapy phase III trial published just 5 minutes ago...that you had no idea ever existed?

Above is the first draft. And I have this weird feeling I left out something obvious. I couldn't find another similar resource. Hopefully together we can make it a living document and helpful resource.

Thank you everyone (including all you misanthropes) for reviewing, commenting, contributing, and hypofractionating.

 

[TheWallnerus]

Have you ever been dunked on hard by medoncs at tumor board, blindsided by the latest immunotherapy phase III trial published just 5 minutes ago...that you had no idea ever existed?

Above is the first draft. And I have this weird feeling I left out something obvious. I couldn't find another similar resource. Hopefully together we can make it a living document and helpful resource.

Thank you everyone (including all you misanthropes) for reviewing, commenting, contributing, and hypofractionating.

Yeah PACIFIC is no longer standard (in theory) if you have stage iii egfr

 

[Neuronix]

https://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-improved-pfs-in-stage-iii-lung-cancer.html

Another great immunotherapy drug !

 

[bevacizzlemab]

https://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-improved-pfs-in-stage-iii-lung-cancer.html

Thanks - Tagrisso osimertinib is an EGFR-TKI targeted therapy right? Maybe we should make a sibling thread for targeted therapy ...any volunteers?

So... potentially resectable NSCLC stage III patients could choose PACIFIC or CheckMate 816. But if unresectable, they could go PACIFIC or (if EGFR mutated) LAURA w/ Tagrisso.

 

[ramsesthenice]

Have you ever been dunked on hard by medoncs at tumor board, blindsided by the latest immunotherapy phase III trial published just 5 minutes ago...that you had no idea ever existed?

Above is the first draft. And I have this weird feeling I left out something obvious. I couldn't find another similar resource. Hopefully together we can make it a living document and helpful resource.

Thank you everyone (including all you misanthropes) for reviewing, commenting, contributing, and hypofractionating.

More likely they dunked on you with a single arm study they think settles the issue now and forever and pass it off for more than it is.

 

[radiaterMike]

I like LAURA more than DEBRA

 

[evilbooyaa]

There is no immunotherapy ph III trial that replaces radiation where one arm received ICI (without radiation) and the other arm received a SOC arm without radiation. ICI that adds on to SOC (like KEYNOTE A18 presented or PACIFIC) may be positive, but is frequently negative (JAVELIN, CALLAS, numerous others). All positive ICI trials compare to an arm that received the same radiation (or not) as the standard arm.

So, no, I've never been 'dunked on' by a Med Onc because none of their ICI trials change my belief as to whether radiation is or is not a valuable portion of the patient's treatment, pre ICI.

Relying on immunotherapy for cure in patients with gross disease is like relying on SBRT alone to cure in oligometastatic disease. A bad idea that may work a small fraction of the time, but a scenario where patients would be much better served by mult-modality therapy. Exception - MMR deficient rectal cancer. Maybe.

 

[medgator]

. A bad idea that may work a small fraction of the time, but a scenario where patients would be much better served by mult-modality therapy. Exception - MMR deficient rectal cancer. Maybe.

N=2 for me so far, but damn they respond

 

[MidwestRadOnc]

I like LAURA more than DEBRA

Either are fine. Just stay away from any iteration of a JESSICA trial, IMO.

 

[drowsy12]

 

[ramsesthenice]

There is no immunotherapy ph III trial that replaces radiation where one arm received ICI (without radiation) and the other arm received a SOC arm without radiation. ICI that adds on to SOC (like KEYNOTE A18 presented or PACIFIC) may be positive, but is frequently negative (JAVELIN, CALLAS, numerous others). All positive ICI trials compare to an arm that received the same radiation (or not) as the standard arm.

So, no, I've never been 'dunked on' by a Med Onc because none of their ICI trials change my belief as to whether radiation is or is not a valuable portion of the patient's treatment, pre ICI.

Relying on immunotherapy for cure in patients with gross disease is like relying on SBRT alone to cure in oligometastatic disease. A bad idea that may work a small fraction of the time, but a scenario where patients would be much better served by mult-modality therapy. Exception - MMR deficient rectal cancer. Maybe.

Spot on. So far, the main thing that IO has replaced is not radiation. Its not surgery. If anything, its chemo. Outside of very specific subsets of tumors (like MMR deficient tumors), essentially all of the checkmate, keynote (etc.) trials have shown that IO is (generally) less toxic than conventional chemo with more durable responses in the subsets that respond.

There is absolutely no real question that ICIs have been the most impactful advancement in clinical oncology over the last decade based simply on the number of diseases for which the offer an OS benefit. But lets make sure we are clear on a couple of things.

1) Are they really paradigm shifting? Based on the definition of the phrase, not really. In most cases, we are simply swapping concurrent chemo for concurrent IO (bladder) or giving it as an adjuvant after standard therapy (esophageal adenocarcinoma, NSCLC). Outcomes are better, but the overall paradigm is more or less the same.

2) Are they curing legions of cancer patients? Again, not really. A more accurate description in most cases is helping turn advanced cancers into a chronic disease. Which again, not a bad thing. We haven't technically cured HIV yet but in case people forgot (or never knew because they were not alive/old enough to remember), the mOS 30 years ago was only about 18 months from the time of diagnosis.

 

[TheWallnerus]

Spot on. So far, the main thing that IO has replaced is not radiation. Its not surgery. If anything, its chemo. Outside of very specific subsets of tumors (like MMR deficient tumors), essentially all of the checkmate, keynote (etc.) trials have shown that IO is (generally) less toxic than conventional chemo with more durable responses in the subsets that respond.

There is absolutely no real question that ICIs have been the most impactful advancement in clinical oncology over the last decade based simply on the number of diseases for which the offer an OS benefit. But lets make sure we are clear on a couple of things.

1) Are they really paradigm shifting? Based on the definition of the phrase, not really. In most cases, we are simply swapping concurrent chemo for concurrent IO (bladder) or giving it as an adjuvant after standard therapy (esophageal adenocarcinoma, NSCLC). Outcomes are better, but the overall paradigm is more or less the same.

2) Are they curing legions of cancer patients? Again, not really. A more accurate description in most cases is helping turn advanced cancers into a chronic disease. Which again, not a bad thing. We haven't technically cured HIV yet but in case people forgot (or never knew because they were not alive/old enough to remember), the mOS 30 years ago was only about 18 months from the time of diagnosis.

Still many unanswered questions though. The number one indication for RT in America is breast cancer. Do women with pCR to Herceptin need radiation? Questions like these. That would be a paradigm shift were the answer “no.”

 

[ramsesthenice]

Still many unanswered questions though. The number one indication for RT in America is breast cancer. Do women with pCR to Herceptin need radiation? Questions like these. That would be a paradigm shift were the answer “no.”

Funny you mention herceptin. It was first approved the year before I started grad school (not to date myself). It was supposed to the be the dawn of the era of targeted therapies which would make chemo and radiation obsolete. That was 1998...

Not downplaying your point. Lots of things could happen. Just pointing out that the big paradigm shift that would totally disrupt cancer therapy has been "just around the corner" for my entire career. Even the example you gave would only apply to a modest subset of the number one indication for RT in America even if it came to fruition. Over the years, it could add up to death by a thousand cuts, but history suggests a swift knockout blow is unlikely.