ESMO 2024

[Palex80]

Hello, everybody!

The ESMO Congress is around the corner, here are some interesting abstracts for RadOnc


Lung

LBA81 - Durvalumab (D) as consolidation therapy in limited-stage SCLC (LS-SCLC): outcomes by prior concurrent chemoradiotherapy (cCRT) regimen and prophylactic cranial irradiation (PCI) use in the ADRIATIC trial


H&N

850MO - Phase II randomized trial of chemotherapy followed by surgery and PORT versus surgery and PORT for organ preservation of T3 and T4a (selected T4b) sinonasal squamous cell carcinoma (SNC): A trial of the ECOG-ACRIN Cancer Research Group (EA3163)

851MO - Final Analysis of a Phase II/III Trial of Post-operative Chemoradiotherapy Comparing 3-Weekly Cisplatin with Weekly Cisplatin in High-risk Patients with Squamous Cell Carcinoma of the Head and Neck (JCOG1008)

LBA37 - Final Results: Randomized Assessment of Cisplatin Dosing Interval for Ototoxicity (RADIO) Trial Comparing Chemoradiation (CRT) with Cisplatin Q3weekly to Weekly for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LASCCHN)

852MO - REWRITE–GORTEC 2018-02: Radiotherapy-durvalumab without prophylactic neck irradiation in squamous cell carcinoma of the head and neck

854MO - Avelumab-cetuximab-radiotherapy (RT) versus standards of care in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): final analysis of randomized phase III GORTEC 2017-01 REACH trial

847O - Sequential chemoradiotherapy versus induction chemotherapy plus concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: A multicentre, open-label, non-inferiority, randomised, phase 3 trial


Gyn

LBA28 - ENGOT-en11/GOG-3053/KEYNOTE-B21: A Phase 3 Study of Pembrolizumab or Placebo in Combination With Adjuvant Chemotherapy With or Without Radiotherapy in Patients With Newly Diagnosed, High-Risk Endometrial Cancer

709O - Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: Overall survival results from the randomized, double-blind, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study



Breast

231O - Locoregional hypo vs normofractionated RT in early breast cancer: 5 years results of the HypoG-01 phase 3 UNICANCER trial



GI

508MO - Organ preservation in early rectal adenocarcinoma: 5-year results of the randomized opera trial

LBA58 - A randomized phase III trial of perioperative chemotherapy (periop CT) with or without preoperative chemoradiotherapy (preop CRT) for resectable gastric cancer (AGITG TOPGEAR): final results from an intergroup trial of AGITG, TROG, EORTC and CCTG



GU

LBA1 - A randomized multicenter open label phase III trial comparing enzalutamide vs a combination of Radium-223 (Ra223) and enzalutamide in asymptomatic or mildly symptomatic patients with bone metastatic castration-resistant prostate cancer (mCRPC): First results of EORTC-GUCG 1333/PEACE-3

LBA71 - Open-label, multicentre randomised trial of Radium223-docetaxel versus docetaxel-Radium223 sequence in Metastatic Castration Resistant Prostate Cancer (mCRPC) with prospective biomarker evaluation (RAPSON study)

1961O - Nivolumab plus chemoradiotherapy in patients with non-metastatic muscle-invasive bladder cancer (nmMIBC), not undergoing cystectomy: a phase II, randomized study by the Hellenic GU Cancer Group.


Lymphoma

812MO - Initial Results of the Multicenter Phase 2 Trial of a Novel Hypofractionated Low-dose Radiotherapy for Indolent non-Hodgkin Lymphoma




Is anyone else coming to the meeting? Send me a DM if you are attending!

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[grenz]

Those are some really interesting studies! Thank you for doing the work, and looking forward to hearing the results

 

[ultima]

I’m not sure what to make of Adriatic being positive but LU-005 being negative (at interim analysis at least) for IO in LS-SCLC.

 

[medgator]

I’m not sure what to make of Adriatic being positive but LU-005 being negative (at interim analysis at least) for IO in LS-SCLC.

I think people are offering durva consolidation now regardless

 

[drowsy12]

I’m not sure what to make of Adriatic being positive but LU-005 being negative (at interim analysis at least) for IO in LS-SCLC.

I think LU005 included concurrent immunotherapy. Concurrent at same time as chemoRT is no good.

 

[Lamount]

I think LU005 included concurrent immunotherapy. Concurrent at same time as chemoRT is no good.

It makes sense -literally nuking the helpful t-cells

 

[goodluck1234]

I’m not sure what to make of Adriatic being positive but LU-005 being negative (at interim analysis at least) for IO in LS-SCLC.

Do you have a source for LU-005? Didn’t realize the interim analysis results were reported.

 

[BobbyHeenan]

Do you have a source for LU-005? Didn’t realize the interim analysis results were reported.

I'm not sure I saw a press release, but I was enrolling and received notification about NRG about it.

 

[drowsy12]

Yeah I also haven’t seen anything about LU005. are we sure it’s negative? That should be public information if it was known or released and I can’t find it online

 

[BobbyHeenan]

Yeah I also haven’t seen anything about LU005. are we sure it’s negative? That should be public information if it was known or released and I can’t find it online

 

[Palex80]

Atezo is a fake drug.

 

[Chartreuse Wombat]

View attachment 391373

DMC dropped the "F" bomb...futility

 

[drowsy12]

View attachment 391373

Thanks!

 

[NotMattSpraker]

View attachment 391373

Ha I am surprised I did not get this, I have enrolled to that trial!

Thats pretty disappointing.

 

[BobbyHeenan]

Ha I am surprised I did not get this, I have enrolled to that trial!

Thats pretty disappointing.

check with your nurse/clinical research staff (site NRG contact). It didn't come to me, it came to one of our clinical research coordinators and they forwarded to me.

 

[NotMattSpraker]

check with your nurse/clinical research staff (site NRG contact). It didn't come to me, it came to one of our clinical research coordinators and they forwarded to me.

Oh haha, yea they are all gone to pharma and I no longer work where I enrolled on this trial. I wouldn't even know who to contact.

SDN continues to be an important resource!

 

[Palex80]

Update with one more interesting abstract

LBA62 - Preoperative modified FOLFIRINOX (mFOLFIRINOX) with or without chemoradiation (CRT) in borderline resectable pancreatic cancer (BRPC): Results from the randomized phase II trial PANDAS/PRODIGE 44​

 

[grenz]

Update with one more interesting abstract

LBA62 - Preoperative modified FOLFIRINOX (mFOLFIRINOX) with or without chemoradiation (CRT) in borderline resectable pancreatic cancer (BRPC): Results from the randomized phase II trial PANDAS/PRODIGE 44​

Has the abstract embargo for ESMO been lifted?

 

[goodluck1234]

 

[seper]

not good

 

[Palex80]

not good

Yes. And we are in a sort of dilemma now.

Should we continue pursuing large-volume, fractionated CRT, including lymphatics? This will obviously lead to a longer time to surgery and/or less systemic treatment.
Should we go only for local treatment of the primary in a hypofractionated manner (SBRT) and ignore lymphatics?

Are we actually asking the question in the right group of patients?

 

[Ray D. Ayshun]

Yes. And we are in a sort of dilemma now.

Should we continue pursuing large-volume, fractionated CRT, including lymphatics? This will obviously lead to a longer time to surgery and/or less systemic treatment.
Should we go only for local treatment of the primary in a hypofractionated manner (SBRT) and ignore lymphatics?

Are we actually asking the question in the right group of patients?

Not a ton of patients, but 15% fewer underwent a major surgery in the CRT arm, yet OS was the same. Did these patients opt against surgery bc pre-op imaging was so good? Also, does ypCR of 30% in CRT arm have to do with extra time to surgery, or does it suggest this might be a good approach in unresectable patients?

 

[drowsy12]

PCR is a meaningless endpoint from a radiation point of view when being compared to non radiation approaches, when/if it doesn’t impact any other outcome

 

[Palex80]

Just watched the ADRIATIC presentation. Excellent work by Suresh Sunan.

BID and PCI were stratification factors in the trial.

Interestingly, 15% absolute DFS benefit in patients who had PCI and BID. Is it all selection bias? I don‘t think so.

 

[medgator]

Just watched the ADRIATIC presentation. Excellent work by Suresh Sunan.

BID and PCI were stratification factors in the trial.

Interestingly, 15% absolute DFS benefit in patients who had PCI and BID. Is it all selection bias? I don‘t think so.

Dose for QD patients was lower than the rtog standard. 60-66 vs 70/35

ClinicalTrials.gov

clinicaltrials.gov

Rtog/calgb intergroup study showed no OS difference between qd and bid, grossly it was better in the QD arm

High-Dose Once-Daily Thoracic Radiotherapy in Limited-Stage Small-Cell Lung Cancer: CALGB 30610 (Alliance)/RTOG 0538 - PubMed

Although 45-Gy twice-daily radiotherapy remains the standard of care, this study provides the most robust information available to help guide the choice of thoracic radiotherapy regimen for patients with limited-stage small-cell lung cancer.

pubmed.ncbi.nlm.nih.gov

 

[Palex80]

Dose for QD patients was lower than the rtog standard. 60-66 vs 70/35

ClinicalTrials.gov

clinicaltrials.gov

Rtog/calgb intergroup study showed no OS difference between qd and bid

True. But 66 Gy is CONVERT. And in that trial qd was „numerically“ inferior to BID.

 

[medgator]

True. But 66 Gy is CONVERT. And in that trial qd was „numerically“ inferior to BID.

Adriatic allowed 60 Gy. I honestly don't think 60 is enough in either nsclc or sclc. But we will never have a trial to show that

 

[Palex80]

Adriatic allowed 60 Gy. I honestly don't think 60 is enough in either nsclc or sclc. But we will never have a trial to show that

It is common practice to give 60 Gy IMHO.
Likely 50% of those who choose to give QD stop somewhere around there. Almost 20% had to stop <66Gy in CONVERT (and those were fit patients, eligible for a clinical trial).

 

[Ray D. Ayshun]

PCR is a meaningless endpoint from a radiation point of view when being compared to non radiation approaches, when/if it doesn’t impact any other outcome

PCR is meaningful in patients who aren't undergoing surgery.

 

[evilbooyaa]

View attachment 392203

Not the ideal result for sure, but for a patient who is getting their ass kicked by FOLFIRINOX after 4 cycles, chemoRT seems like a reasonable alternative to achieve similar oncologic outcome rather than losing out additional benefit of 6 cycles of chemo. And that's not including the imbalance with double the # of patients due to progression (which we know is the only way any of those patients are going to be cured as they received palliative dose EBRT). Was that because 4 cycles of FOLFIRINOX is not enough to 'minimize' chances of DM?

Would be interested in difference in LRF vs DM between the two arms.

 

[evilbooyaa]

PCR is meaningful in patients who aren't undergoing surgery.

Yeah but 50.4/28 is not an EBRT dose that should be used in 2024 in patients not going for surgery unless your goal is palliation.

 

[communitydoc13]

View attachment 392203

Functionally such a small trial with associated imbalances (the CA 19-9 numbers are wildly different).

Still...if I were to try to come up with a narrative to explain the results, it would be the same one we have been aware of for a long time.

Pancreatic cancer is just waiting to met out. Perhaps 6 cycles of chemo with rapid turnaround to surgery is the best way not to find distant progression prior to surgery (hence the greater number of surgical patients in the chemo only arm).

This likely explains the difference in survival among surgerized patients. (In the chemorads arm... those patients that metastasized prior to surgery are excluded from the analysis of surgerized patients...skewing the outcomes).

Concurrent chemoradiation is a reasonable option for inoperable patients, particularly those who have exhausted chemo due to tolerance.

 

[communitydoc13]

Yeah but 50.4/28 is not an EBRT dose that should be used in 2024 in patients not going for surgery unless your goal is palliation.

I don't know. Not all patients are good SBRT candidates and dose escalation comes with risks. Sure, most of us would try to get to 54 or 55.8 (or more) in standard fractionation, but the vast majority of patients are not benefiting from dose escalation.

 

[Ray D. Ayshun]

Yeah but 50.4/28 is not an EBRT dose that should be used in 2024 in patients not going for surgery unless your goal is palliation.

I don't necessarily disagree, but is this the first randomized trial where 50.4 was given after FOLFIRINOX?

 

[yesmaster]

Why are fewer patients getting to surgery after chemoXRT?

It’s encouraging to me that arm A and arm B are roughly equivalent and the best-performing group of patients had mFolfirinox plus chemoXRT. If chemotherapy was the only helpful treatment, there’s no reason that OS would be higher for only 4 cycles mFolfirinox plus chemoXRT then surgery, at best it would be equivalent.

 

[BobbyHeenan]

Why are fewer patients getting to surgery after chemoXRT?

It’s encouraging to me that arm A and arm B are roughly equivalent and the best-performing group of patients had mFolfirinox plus chemoXRT. If chemotherapy was the only helpful treatment, there’s no reason that OS would be higher for only 4 cycles mFolfirinox plus chemoXRT then surgery, at best it would be equivalent.

This was my take as well though I didn't take a deep dive. Was it due to toxicity or just imbalance in arms or progression to mets while getting chemo-XRT.

If super fit then give them radiation?

If borderline fitness and the toxicity of chemo-XRT is a risk to knock them out then maybe omit the radiation?

 

[communitydoc13]

Why are fewer patients getting to surgery after chemoXRT?

It’s encouraging to me that arm A and arm B are roughly equivalent and the best-performing group of patients had mFolfirinox plus chemoXRT. If chemotherapy was the only helpful treatment, there’s no reason that OS would be higher for only 4 cycles mFolfirinox plus chemoXRT then surgery, at best it would be equivalent.

Per my interpretation, it was because more non-local progression was observed in the chemoXRT arm. (per the abstract, tumor progression 7 vs 13 patients, and they have a separate category for unresectable disease).

This could explain the better outcomes for surgical patients who received chemorads. An additional 6 patients weren't operated on because they had demonstrable distant progression prior to surgery (which may have been suppressed by continued multiagent chemotherapy and short interval to surgery).

In other words, chemo followed by chemoXRT is better at selecting out favorable surgical patients than chemo alone.

We have not come out as winners in this space.

Preoperative mFOLFIRINOX With vs Without Hypofractionated Radiotherapy for Borderline Resectable PDAC

This randomized clinical trial compares treatment with neoadjuvant modified FOLFIRINOX with or without hypofractionated radiation therapy with historical data and establishes standards for therapy in borderline resectable pancreatic ductal adenocarcinoma.

jamanetwork.com

Another super small, infuriating and XRT negative (almost like killing patients negative) trial.

 

[Palex80]

Why are fewer patients getting to surgery after chemoXRT?

It’s encouraging to me that arm A and arm B are roughly equivalent and the best-performing group of patients had mFolfirinox plus chemoXRT. If chemotherapy was the only helpful treatment, there’s no reason that OS would be higher for only 4 cycles mFolfirinox plus chemoXRT then surgery, at best it would be equivalent.

Well, the trial was designed for borderline resectable tumors. I presume the hypothesis was that RT would lead to more local remissions / downsizing and facilitate higher rates of complete resection.

 

[seper]

fewer patients in RT arm are going to Whipple. This may mean traditional IMRT is too toxic after FOLFIRINOX. juts a thought

 

[Doctorer]

fewer patients in RT arm are going to Whipple. This may mean traditional IMRT is too toxic after FOLFIRINOX. juts a thought

Or it's what you get when you're running a smaller trial.

I haven't seen a significant difference between acute toxicity in patients getting proton/photon neoadjuvant treatment, if that's what you're getting at.

 

[BobbyHeenan]

fewer patients in RT arm are going to Whipple. This may mean traditional IMRT is too toxic after FOLFIRINOX. juts a thought

This may very well be the case.

I'm sure they have data on why each person didn't go to trial. Small numbers but the question of met'd out vs. not fit enough after IMRT should give some partial clarity.

Was that presented? Looks like @communitydoc13 saw something like that.

 

[communitydoc13]

fewer patients in RT arm are going to Whipple. This may mean traditional IMRT is too toxic after FOLFIRINOX. juts a thought

They address this in the abstract. The difference is due to differences in observed progression. (adverse events, physician decision all very low numbers)

 

[ramsesthenice]

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Some of these interpretations blow my mind. The assumption going into this was clearly that radiation is bad and toxic and should be avoided if possible. Was arm B any more toxic than arm A? No, but it just has to be because its hot and burns things unlike the cooling elixir that is chemo.

An equally plausible interpretation is that chemoradiation did a better job of selecting the appropriate patients for surgery than chemo alone without compromising survival or disease control. Further, the best survival was seen in the patients who got all 3 modalities. By over a f****** year!!! I admit, I would have expected to see a better R- resection rate in the RT arm and the pathologic response rates make that even more confusing but be it as it may, this data makes me even more inclined to continue treating BRPC. I sincerely hope the oral presentation and final publication will be more thoughtful in their interpretation of the data.

 

[communitydoc13]

this data makes me even more inclined to continue treating BRPC

This data doesn't change anything I do, which is participate in neoadjuvant care when asked.

I cannot take the difference in OS for surgerized patients in this study too seriously (small trial, unplanned subset, differential selection of patients based on pre-op treatment, etc). I don't think we can counsel patients that XRT is going to make them live longer on average.

But I agree if the toxicity difference is not significant, one could argue for trimodality therapy on the following basis.

1. Some patients met out while receiving chemorads and avoid unnecessary surgery. (Presumable they will get some LC benefit from XRT). Definitely need that post-XRT-pre-op scan.

2. Many patients won't get operated on for reasons other than distant progression (certainly true in the real world, where medically marginal patients are often strung along in my experience). Some of these patients (not a trivial number) will have achieved a local CR by getting chemoXRT.

I think in reality, some surgeons and medoncs may interpret this another way...that if chemoXRT compromises the likelihood of surgery, it must be a negative.

 

[BobbyHeenan]

This data doesn't change anything I do, which is participate in neoadjuvant care when asked.

I cannot take the difference in OS for surgerized patients in this study too seriously (small trial, unplanned subset, differential selection of patients based on pre-op treatment, etc). I don't think we can counsel patients that XRT is going to make them live longer on average.

But I agree if the toxicity difference is not significant, one could argue for trimodality therapy on the following basis.

1. Some patients met out while receiving chemorads and avoid unnecessary surgery. (Presumable they will get some LC benefit from XRT). Definitely need that post-XRT-pre-op scan.

2. Many patients won't get operated on for reasons other than distant progression (certainly true in the real world, where medically marginal patients are often strung along in my experience). Some of these patients (not a trivial number) will have achieved a local CR by getting chemoXRT.

I think in reality, some surgeons and medoncs may interpret this another way...that if chemoXRT compromises the likelihood of surgery, it must be a negative.

I can tell you for sure at my cancer center it will still come down to one thing....

Does the surg onc want the patient to get pre-op XRT? It doesn't matter what I say. The work flow in my world will be med onc and surg onc first then they'll cherry pick ones they want to send later.

If you're treating pre-op too you better be damn sure you take excellent care of these patients as far as symptom and weight /calorie management goes as well. Nothing like pissing off a surgeon if a post XRT patient walks back in their clinic looking awful. In these cases, I can tell you in my experience that aggressive symptom management and having a good nurse navigator and supportive care team can really help.

 

[ramsesthenice]

I can tell you for sure at my cancer center it will still come down to one thing....

Does the surg onc want the patient to get pre-op XRT? It doesn't matter what I say. The work flow in my world will be med onc and surg onc first then they'll cherry pick ones they want to send later.

If you're treating pre-op too you better be damn sure you take excellent care of these patients as far as symptom and weight /calorie management goes as well. Nothing like pissing off a surgeon if a post XRT patient walks back in their clinic looking awful. In these cases, I can tell you in my experience that aggressive symptom management and having a good nurse navigator and supportive care team can really help.

Ding ding ding. This where I know I am safe as well. Ours a quite pro radiation. Even with IRE.

This data doesn't change anything I do, which is participate in neoadjuvant care when asked.

I cannot take the difference in OS for surgerized patients in this study too seriously (small trial, unplanned subset, differential selection of patients based on pre-op treatment, etc). I don't think we can counsel patients that XRT is going to make them live longer on average.

But I agree if the toxicity difference is not significant, one could argue for trimodality therapy on the following basis.

1. Some patients met out while receiving chemorads and avoid unnecessary surgery. (Presumable they will get some LC benefit from XRT). Definitely need that post-XRT-pre-op scan.

2. Many patients won't get operated on for reasons other than distant progression (certainly true in the real world, where medically marginal patients are often strung along in my experience). Some of these patients (not a trivial number) will have achieved a local CR by getting chemoXRT.

I think in reality, some surgeons and medoncs may interpret this another way...that if chemoXRT compromises the likelihood of surgery, it must be a negative.

100% agree I wouldn’t tell anyone radiation improves survival. But at the same time, that post hoc still had over 100 patients and discounting it as a superfluous finding would be a mistake IMO. That’s a very strong signal and as a whole makes sense. Local recurrences as a first site of failure after surgery are fairly common in patients after neoadjuvant therapy and the very good pathologic responses make it very plausible CRT would add benefit on top of triplet chemo. Both arms are SOC options and this would do nothing to tell me one should be made a top line recommendation. Further, I 100% guarantee if they saw the exact same results with chemo vs chemo + IO, they would probably have already proclaimed chemo + IO the new SOC.

The other thing is I wouldn’t be surprised if a lot of Whipple surgeons would still favor radiation. Their worst fear is doing surgery and seeing nets on the next scan (which is probably what these patients were destined for since survival still isn’t different). Many of the thoughtful surgeons I know probably won’t look at this as compromising the ability to have surgery as much as avoiding an unnecessary operation.

 

[drowsy12]

'Further, I 100% guarantee if they saw the exact same results with chemo vs chemo + IO, they would probably have already proclaimed chemo + IO the new SOC.'

well pCR is a more useful outcome for a systemic therapy change, at least it means it's working elsewhere too.

 

[goodluck1234]

Some thoughts on the lung cancer abstracts...

1. ADRIATIC - abstract and NEJM publication
-In the control arm, only 24% of those who received salvage therapy had immunotherapy as part of their treatment. Kudos to Jeff R for pointing this out, as usual. Still, with such a strong OS signal, even if that number were ~70%, there might still be a benefit. But we'll never know.
-The BID vs QD and PCI vs no PCI comparisons (BID and PCI both did better) are interesting but very much hypothesis-generating. The authors' main message is that the benefit of durvalumab persisted across these subgroups. We have randomized trials comparing QD to BID, and we have the ongoing MAVERICK study for the PCI question, so I personally would not overinterpret these non-randomized comparisons. The real question is how does 70 Gy QD compare to dose-escalated BID (54 or 60 Gy), and whether dose-escalated BID is ok prior to consolidation durvalumab.

2. LBA48 - CCTG BR.31: A global, double-blind placebo-controlled, randomized phase III study of adjuvant durvalumab in completely resected non-small cell lung cancer (NSCLC)

I think this is an important negative study. For early stage NSCLC treated with R0 resection, adjuvant durvalumab did not improve DFS regardless of PD-L1 status. Makes one question the adjuvant atezo study which has been used to push adjuvant atezo on everyone with PD-L1 >=1%.

3. Not from ESMO, but 2 of the 3 SBRT +/- immunotherapy phase 3 trials for early stage NSCLC are apparently negative for PFS, including the KEYNOTE study and the SWOG study. Not looking good for PACIFIC-4. Another example of phase II data (Joe Chang MDACC trial) not translating into phase III benefits.

 

[ramsesthenice]

'Further, I 100% guarantee if they saw the exact same results with chemo vs chemo + IO, they would probably have already proclaimed chemo + IO the new SOC.'

well pCR is a more useful outcome for a systemic therapy change, at least it means it's working elsewhere too.

I wasn't talking about the pCR. I was referring to the unplanned subset analysis showing a trend towards improved survival in arm B. I wish I were kidding, but IO has gotten approved indications for less in the past. If it were IO instead of CRT, you may seriously have a new option.

BTW, the 100% guarantee was made tongue and cheek. I have more faith in our approval process than that...but have been surprised before non-the-less.

 

[Palex80]

-In the control arm, only 24% of those who received salvage therapy had immunotherapy as part of their treatment.

1. IO adds 2-3 mOS in metastatic SCLC.
2. If the patient fails early (<6mo) after CRT, salvage CT is usually not platin-based, and thus no IO is given. Patients usually get Topotecan or some other non-platin based salvage regime.