Top Clinical Trials from ESTRO

[Gfunk6]

PLATO ACT 4 - early stage anal cancer, dose de-escalation

T1-T2, <= 4 cm N0

Arm 1: 41.4 Gy in 23 fx
Arm 2: 50.4 in 28 fx

2:1 randomization, concurrent chemo = Capecitabine, MMC x1

3 year local-regional failure free rate:
Arm 1: 87.6%
Arm 2: 83.6%

3 year OS:
Arm 1: 98.1%
Arm 2; 92.6%

Conclusion: Reduced dose radiation should be standard of care in early stage anal cancer

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[Gfunk6]

STAR-TREC - Chemoradiation (50 in 25 with capecitabine) vs 5x5 Gy short course RT for early stage rectal cancer

cT1-T3b N0 (70% were T2), < 4 cm

Treating Meaorectum ONLY (50% volume reduction)

With either radiation arm, if cCR then surgery was deferred in favor of surveillance

12 month TME free survival
80%: long course
61%: short course

30-month outcome planned

Conclusion (preliminary): Short course XRT appears less effective that long course for pre op treatment for early-intermediate stage rectal cancer

 

[Gfunk6]

PRIME-RT - Durvalumab with extended TNT regimens in locally advanced rectal cancer

T1-T4, N1-N2

Arm A: FOLFOX x 6c with IO plus SCRT (at start)
Arm B: FOLFOX x 4c with IO plus LCRT + capecitabine (at start)

cCR @ 18 months
Arm A: 48%
Arm B: 33%

38% grade 3-5 tox on Arm A vs 9% on Arm B

Conclusion: SCRT is superior in this scenario, possibly reflecting divergent immuno-modulatory effects with hypo-fractionated RT

 

[Gfunk6]

STELLAR - Short course XRT + chemo for locally adjacent rectal cancer

T3/T4 or N+

Arm 1: pre-op SCRT —> surgery —> adjuvant chemo
Arm 2: Neoadjuvant FOLFOX —> surgery

No significant differences in DFS but provides 8.4% improvement in OS at 5 years in Arm 2 which should be the standard of care in LA-CRC

 

[Gfunk6]

STELLAR 2 - SCRT —> chemotherapy plus IO for LARC

Arm 1: SCRT —> CapeOX —> TME vs WW
Arm 2: SCRT —> CapeOX + IO —> TME vs WW

cCR rate
Arm 1: 25%
Arm 2: 45.5%

Conclusion: Addition of IO to TNT with SCRT appears to be more effective than standard TNT.

 

[HemeOncHopeful19]

PLATO ACT 4 - early stage anal cancer, dose de-escalation

T1-T2, <= 4 cm NO

Arm 1: 41.4 Gy in 23 fx
Arm 2: 50.4 in 28 fx

2:1 randomization, concurrent chemo = Capecitabine, MMC x1

3 year local-regional failure free rate:
Arm 1: 87.6%
Arm 2: 83.6%

3 year OS:
Arm 1: 98.1%
Arm 2; 92.6%

Conclusion: Reduced dose radiation should be standard of care in early stage anal cancer

One less dose of MMC sounds awesome to me can we get a study cooking in N+ disease too please

 

[brushbeamscanning]

One less dose of MMC sounds awesome to me can we get a study cooking in N+ disease too please

it's fine for N+, it's a standard option in the UK (12 mg/m2 on d1 not 10 mg/m2 on d1 and d29) that was done in ACT II where 1/3rd had N+ disease. It's also a suggested option in the latest ASTRO Anal cancer guidelines and NCCN.

 

[ramsesthenice]

PLATO ACT 4 - early stage anal cancer, dose de-escalation

T1-T2, <= 4 cm NO

Arm 1: 41.4 Gy in 23 fx
Arm 2: 50.4 in 28 fx

2:1 randomization, concurrent chemo = Capecitabine, MMC x1

3 year local-regional failure free rate:
Arm 1: 87.6%
Arm 2: 83.6%

3 year OS:
Arm 1: 98.1%
Arm 2; 92.6%

Conclusion: Reduced dose radiation should be standard of care in early stage anal cancer

I’ve treated these to 45 for years. Not at all surprised.

What I am about to say will surprise some of you since I have traditionally been a SCRT proponent for rectal cancer. I would really like to see late toxicity follow up with concurrent IO. I recently reviewed data that is not published yet, so I can’t share specifics. There certainly appears to be something to the efficacy story (unlike LC + pembro in GI-001) but may come at a non-trivial cost. I’m not poo-pooing the general idea. It’s starting to look like not all IO is the same when you start mixing regimens and there are just some details to work out.

 

[Gfunk6]

STORM- Prostate cancer s/p RP/XRT with biochemical failure and positive disease on PSMA PET

Most of patient had a solitary lymph node

Arm 1: ENRT to regional nodes + 6 mo ADT
Arm 2: SBRT to positive nodes + 6 mo ADT

3 year biochemical relapse free survival:

Arm 1: 69%
Arm 2: 47%

Locoregional repulse free survival

Arm 1: 90%
Arm 2: 70%

In the setting of previous radical therapy for prostate cancer ENRT appears superior to SBRT.
——————————

It should be pointed out that the systemic therapy in this trial is considered inferior by modern day standards. EMBARK used ADT + enzalutamide (median duration 17 mo). In this scenario, SBRT is favored for oligomets and ENRT for locoregional failure (bed +- LNs).

 

[Gfunk6]

FLAME - Standard prostate fractionation +- SIB boost to gross disease

Int-High risk (84% high risk)
Lymph nodes NOT treated

Arm 1- 77 Gy in 35
Arm 2 - as above but up to 95 Gy via SIB to lesions (median 84.7 Gy)

ADT given at the discretion of the investigator
1/3 did not get ADT

10 year bPFS
Arm 1 - 71%
Arm 2 - 86%

10 year DFS
Arm 1 - 67%
Arm 2 - 81%

10 year regional LN DFS
Arm 1 - 84%
Arm 2 - 95%

No difference in toxicity in both arms.

SIB shows unequivocal long term clinical advantages compared to more homogenous conventional dosing.

Multiple trials using hypofrac and SBRT trials underway based on the above.

 

[Gfunk6]

Phase II - Nivolumab + CRT In muscle invasive bladder cancer

cT2-T4aN0M0

All patients had vigorous TURBT but were otherwise surgically ineligble

Arm 1: 60 Gy to bladder + 10 Gy boost + CDDP
Arm 2: As above + nivolumab

2 year OS
Arm 1: 60.5%
Arm 2: 86.8%

No differences in Gr3+ tox in either arm

These results warrant a followup Phase III trial

 

[Gfunk6]

ARISTOTLE - Standard preop CRT (45 Gy in 25 fx) for rectal cancer +- irinotecan

No change in 3 year DFS, LRF, DM , OS in either arm

No justification of adding irinotecan to traditional CRT with 5FU

 

[Palex80]

EMBRACE used ADT + enzalutamide (median duration 17 mo).

I presume, you mean EMBARK?

EMBARK on the other hand did not include patients with oligometastasis on PSMA-PET-CT staging, but only patients with BCR and "seemless" cN0 cM0, based on CT-staging. I am saying "seemless", because if you have a look at the protocol of EMBARK, patients could go on trial with what we would define as "pathologic" nodes on CT, as long as those did not surpass a certain threshold.
From the protocol
Patients with softtissue pelvic disease may be eligible if the short axis of the largest lymph node is< 20 mm for lymph nodes below aortic bifurcation.

I strongly believe, that the study populations of STORM and EMBARK are not the same.

 

[Palex80]

PRIME-RT - Durvalumab with extended TNT regimens in locally advanced rectal cancer

T1-T4, N1-N2

Arm A: FOLFOX x 6c with IO plus SCRT (at start)
Arm B: FOLFOX x 4c with IO plus LCRT + capecitabine (at start)

cCR @ 18 months
Arm A: 48%
Arm B: 33%

38% grade 3-5 tox on Arm A vs 9% on Arm B

Conclusion: SCRT is superior in this scenario, possibly reflecting divergent immuno-modulatory effects with hypo-fractionated RT

What I do not understand about this trial, as well as other trials in rectal cancer giving IO on top of RT/CRT, is the following thing:

Do we think that all patients would benefit, or is the benefit observed with IO guided by a subgroup of patients in the trials with a specific biomarker.
We know that in colorectal cancer IO works the best in patients with MMR-deficiency. Those trials did not select patients based on biomarkers (and they all started recruting before the MSKCC-data with IO-monotherapy came out - "the-19-patients-NEJM-paper").

So, is IO reasonable on top of any neoadjuvant treatment (or organ preservation strategy) for rectal cancer in molecularly unselected patients?

 

[medgator]

The real question @Gfunk6 is how is Vienna?

More interesting trial reporting at estro, guessing the meeting locations are better too

 

[Gfunk6]

Vienna is fantastic. Beautiful city, just a unique fusion of modern and Hapsburg architecture. Paid for a 7 day mass transit pass ~ $30. I can get anywhere in the city within 30-40 min tops without having to pay for an Uber.

The things that you can do outside the conference, culturally, so far exceeds the typical US city, it is almost laughable.

I find the content of the meeting far superior to ASTRO. Better organized, higher yield, real science and interesting discussions.

For my purposes, ESTRO is superior to ASTRO in every way.

 

[thesauce]

FLAME - Standard prostate fractionation +- SIB boost to gross disease

Int-High risk (84% high risk)
Lymph nodes NOT treated

Arm 1- 77 Gy in 35
Arm 2 - as above but up to 95 Gy via SIB to lesions (median 84.7 Gy)

ADT given at the discretion of the investigator
1/3 did not get ADT

10 year bPFS
Arm 1 - 71%
Arm 2 - 86%

10 year DFS
Arm 1 - 67%
Arm 2 - 81%

10 year regional LN DFS
Arm 1 - 84%
Arm 2 - 95%

No difference in toxicity in both arms.

SIB shows unequivocal long term clinical advantages compared to more homogenous conventional dosing.

Multiple trials using hypofrac and SBRT trials underway based on the above.

Do you have a link for this?

 

[Gfunk6]

Do you have a link for this?

This link was posted just three hours ago

FLAME Trial at ESTRO 2025. Focal Boost to the intraprostatic tumor for intermediate and high risk prostate cancer: 10-year Results - OncoDaily

FLAME Trial at ESTRO 2025. Focal Boost to the intraprostatic tumor for intermediate and high risk prostate cancer: 10-year Results / cancer, ESTRO, ESTRO2025,

oncodaily.com

 

[madchemist89]

I like FLAME, but it goes against the trend toward hypofractionation. I have seen people use hypofrac and do SIB, but this would have been off trial as far as I know. Can we do FLAME in US with insurers the way they are or is it dead here unless you incorporate that into a hypofrac plan? Do we have safety data on that approach?

 

[Palex80]

The things that you can do outside the conference, culturally, so far exceeds the typical US city, it is almost laughable.

Dude, it's Vienna!
🙂

Next is year is Stockholm, I might go. Had to stay in the clinic this year.

 

[OTN]

I like FLAME, but it goes against the trend toward hypofractionation. I have seen people use hypofrac and do SIB, but this would have been off trial as far as I know. Can we do FLAME in US with insurers the way they are or is it dead here unless you incorporate that into a hypofrac plan? Do we have safety data on that approach?

I haven't had any pushback from US insurers whatsoever when it comes to FLAME. It's my go to for high risk patients.

 

[Gfunk6]

I haven't had any pushback from US insurers whatsoever when it comes to FLAME. It's my go to for high risk patients.

The funny thing is that FLAME did not include nodal radiation. However to get conventional frac approved by payors, you have to explicitly state that you are treating lymph nodes.

 

[ramsesthenice]

It should be pointed out that the systemic therapy in this trial is considered inferior by modern day standards. EMBARK used ADT + enzalutamide (median duration 17 mo). In this scenario, SBRT is favored for oligomets and ENRT for locoregional failure (bed +- LNs).

I personally don't think its that simple. If someone has a single positive node on PYL-PET-imaging with multiple high risk features (say negative surgical margins and failure within 12 months of primary therapy), they almost certainly don't really have oligomets, and I would be more comprehensive. I was way more gunho about SBRT early on but it quickly became pretty clear that traditional clinical predictors (duration of control, PSA velocity, margin status, etc) can help you figure out when SBRT has a reasonable chance of delaying progression or not. Good thing is, if you guess wrong, you can usually still try the other approach.

I haven't had any pushback from US insurers whatsoever when it comes to FLAME. It's my go to for high risk patients.

Fortunately, Im in the same boat you are. I use it for UFIR patients with a DIL on either MRI or PYL imaging without treating nodes and so far, I have not had a single denial for fraction number. I've had to defend using IMRT and or IGRT, but always gotten it. I can't help but feel like im living on borrowed time before they start pushing back on 35 fractions...

 

[StIGMA]

What I do not understand about this trial, as well as other trials in rectal cancer giving IO on top of RT/CRT, is the following thing:

Do we think that all patients would benefit, or is the benefit observed with IO guided by a subgroup of patients in the trials with a specific biomarker.
We know that in colorectal cancer IO works the best in patients with MMR-deficiency. Those trials did not select patients based on biomarkers (and they all started recruting before the MSKCC-data with IO-monotherapy came out - "the-19-patients-NEJM-paper").

So, is IO reasonable on top of any neoadjuvant treatment (or organ preservation strategy) for rectal cancer in molecularly unselected patients?

This is completely undefined right now. This was only initiated as an exploratory phase 2 (feasibility). There are non-PD1/PDL1-dependent factors (as one example) but not in a way that has been sorted out yet. This trial is the right idea but it is too early even begin discussing a phase 3 imo. I would wait until IO is approved in MMR proficient subsets in metastatic and use that as inclusion for ph3.

 

[ramsesthenice]

This is completely undefined right now. This was only initiated as an exploratory phase 2 (feasibility). There are non-PD1/PDL1-dependent factors (as one example) but not in a way that has been sorted out yet. This trial is the right idea but it is too early even begin discussing a phase 3 imo. I would wait until IO is approved in MMR proficient subsets in metastatic and use that as inclusion for ph3.

Very unclear. I'll be honest, some of the cervial/endometrial trials are getting good results in a more tumor agnostic manner than I would have expected with different systemic combinations (example, MSS subgroup in the RUBY trial). Some rectal trials are also looking like its not just the MMRd patients who may benefit but there are many caveats. Just giving them IO does nothing. Just giving it with LC CRT doesn't seem to do anything. And when it does work, the effect isn't even close to what you see in MMRd patients. More like what you see above with a meaningful improvement in local responses, but not a magical cure.

Its a very long way of saying there probably is a role for IO in MMRp patients. At least more than I would have assumed previously. Hopefully there are better biomarkers eventually. And clearly, we are far from knowing how to best put it all together. I do think there is something to the SCRT. Plenty of studies have shown that MHC tumor antigen presentation after RT is highly dose dependent. So there is a reason to think hypofrac "could" (and I stress could) at least hypothetically make it easier for the immune system to recognize tumors with a lower antigenic burden.

If someone wanted to take one of the above studies to phase 3, fine. I just hope they would do good correlatives to help us know where to look in future studies to address some of these issues. Still lots to figure out and really get this right.

 

[DoctwoB]

Phase II - Nivolumab + CRT In muscle invasive bladder cancer

cT2-T4aN0M0

All patients had vigorous TURBT but were otherwise surgically ineligble

Arm 1: 60 Gy to bladder + 10 Gy boost + CDDP
Arm 2: As above + nivolumab

2 year OS
Arm 1: 60.5%
Arm 2: 86.8%

No differences in Gr3+ tox in either arm

These results warrant a followup Phase III trial

Very interesting, few questions for you guys.

1. Is CRT usually done with cisplatin as here? Usually seen with 5-FU or other agents if i recall correctly.
2. Any data on xrt + antibody/conjugate drugs like enfortumab vedotin? Given EV-Pembro is now SOC in metastatic TCC, and have a suspicion will become so in the neoadjuvant setting based on ongoing trials, wonder if any trials looking at EV-Pembro + XRT are in the works.

 

[thesauce]

I like FLAME, but it goes against the trend toward hypofractionation. I have seen people use hypofrac and do SIB, but this would have been off trial as far as I know. Can we do FLAME in US with insurers the way they are or is it dead here unless you incorporate that into a hypofrac plan? Do we have safety data on that approach?

I wouldn’t hypofrac in a flame-boost scenario but the trend does seems to be swinging back towards more fractions. As much as many want to control to narrative and push for a certain approach (likely to attract more out of towners), the data is becoming clear that a more standard fractionation is safer and more effective and it’s especially easy to justify in a flame-boost type scenario. How you are compensated will entirely depend on your contracts.

 

[Palex80]

1. Is CRT usually done with cisplatin as here? Usually seen with 5-FU or other agents if i recall correctly.

This is likely country-specific in Europe. In the UK lot's of MMC, in mainland Europe, esp. Germany, cisplatin/carboplatin

2. Any data on xrt + antibody/conjugate drugs like enfortumab vedotin? Given EV-Pembro is now SOC in metastatic TCC, and have a suspicion will become so in the neoadjuvant setting based on ongoing trials, wonder if any trials looking at EV-Pembro + XRT are in the works.

Trials are running, for example

UCSF Bladder Cancer Trial: Enfortumab Vedotin and Pembrolizumab Combined With Radiotherapy in Muscle Invasive Bladder Cancer

This Bladder Cancer and Urinary Bladder Tumor study at UCSF is now recruiting people ages 18 years and up.

clinicaltrials.ucsf.edu

 

[evilbooyaa]

Very interesting, few questions for you guys.

1. Is CRT usually done with cisplatin as here? Usually seen with 5-FU or other agents if i recall correctly.
2. Any data on xrt + antibody/conjugate drugs like enfortumab vedotin? Given EV-Pembro is now SOC in metastatic TCC, and have a suspicion will become so in the neoadjuvant setting based on ongoing trials, wonder if any trials looking at EV-Pembro + XRT are in the works.

Usually the folks w/ bladder Ca I treat are generally pretty poor performance status and are getting the twice weekly low dose Gem regimen. Really good folks can consider 5-FU/Cis. Occasionally Cis alone. It's more dependent on potential tolerability of treatment than anything else. I have not seen 5-FU/MMC, as was done in BC2001, in my pt population.

ADCs need to be studied w/ RT especially to definitive doses - not nearly as 'free' as most ICIs in terms of combining with RT.

Really interesting series of studies presented. I'm confused as to the obsession with ICI in rectal cancer. All studies need to report some form of analysis, even if post-hoc, between MMRd and MMRp when talking about sprinkling IO into rectal cancer...

 

[medgator]

Really interesting series of studies presented. I'm confused as to the obsession with ICI in rectal cancer. All studies need to report some form of analysis, even if post-hoc, between MMRd and MMRp when talking about sprinkling IO into rectal cancer...

Not sure we are seeing any of the MMRd patients these days though? I thought the study was looking specifically at the proficient population