Thread by @JenSeligmann

🥁🥁🥁Tweetorial
FOxTROT, the 1st ph 3 RCT of neoadjuvant chemo (NAC) in locally advanced colon cancer
We report that NAC is
✅deliverable and safe
✅led to statistically significant reduction in cancer recurrence than upfront surgery
A 🧵 (1/14)
#crcsm
ascopubs.org/doi/full/10.12…

2/14 The trial:
⭕️moved 6 weeks of chemo ahead of surgery, vs standard treatment.
⭕️Same total duration of chemo in each arm (pre-IDEA so total duration 24 weeks)
⭕️ primary endpoint 2 year RFS
1053 pts from 85 centres in 3 countries

3/14
🥁 Primary endpoint is met. 6 weeks of NAC led to:
✅ 28% relative reduction in 2 year recurrence
✅ 31% relative reduction in 3 year DFS

These data have strengthened since preliminary data presented and are final with mature follow up

4/14 - looking instead at disease-free survival, NAC also shows statistically significant improvement at 2 and 3 years, and maintained after longer follow up

5/14 With NAC:
✅ No reduction in pts proceeding to surgery
✅ Compromised resection margins ⬇️ by 50%
✅ Strong trend to fewer surgical complications
✅ Major pathological downstaging of tumor and nodes

6/14
So, if NAC improved outcomes for whole trial population, should everyone now get it?
Not unreasonable, & standard of care now in many centres…
BUT – some benefit more than others
👍 proficient MMR/ MSS tumors
👍T4 tumours
👍left sided tumours

7/14
BUT...can we select pts for NAC using CT staging?
✅ Positive trial - benefit of NAC seen using this criteria
✅ Difference in RFS by T-stage
✅ V low proportion T1/T2 pts enrolled
⛔️ Nodal status less accurate esp in dMMR pts

doi.org/10.1016/j.ejca…

8/14 Wait, there’s more…
In pMMR tumors, histological response in resected tumor was strongly associated with longer term outcomes
💥 No recurrences in pts with pCR
😐 ⬇️NAC response 🟰 ⬆️rate of relapse
✅Future use as early efficacy surrogate endpoint

9/14
Does FOxTROT support a new SOC?
✅new rx option to be considered 🙏T4 pts at least
🤔Do we wait >5-10 years for validation – it is a ph3 trial that met primary endpoint!
🤔 If we had seen a result this dramatic for a new drug in a ph 3 trial would this now be SOC?

10/14
What next...?
@FoxtrotStudy Platform @yorkshirecancer
OPEN IN UK
👍FOxTROT 2 - NAC in older pts
👍FOxTROT 3 - NAC with mFOLFOXIRI
COMING SOON
👍 FOxTROT 4 - Enco/Cetux in BRAF-mut pts
👍FOxTROT HER2 - Tucatinib/Tras in HER2 +ve pts
👍FOxTROT-IO - watch for news soon 😉

11/14
FOxTROT Platform open in centres across the UK; soon to open in France and India.
Recruiting in UK; opening soon in France and India. Other partners soon to join🤝
Contact us - we would love to work with you

12/14
More data to come:
👍 panitumumab + NAC with extended biomarker
👍risk of obstruction @DrJamesGlasbey
👍Histopath 'deep dive' and tumor immunology
👍Genomics 'deep dive' looking at response/ resistance
👍radiology 'deep dive' & AI
>900 matched tumor biopsy/resections 👍

13/14
Thank you…
💛The pts who participated in our research
💛The pts who guide our research
👍Our main funders @CRUKresearch;also @yorkshirecancer @NCRI_partners
🤝 Our collaborators in Sweden and Denmark
💜 Our FOxTROT Investigators

Finally, 👏the original Team FOxTROT who worked so hard on this trial for 15 years.
@BhamCTU Laura Magill Richard Grey Kelly Handley
@Leedspath Phil Quirke & Nick West
@prof_gina_brown
Bengt Glimelius & Soeren Laurberg
And of course @seymourmatt1 & Dion Morton @UoBSurgery

@CRUKresearch @OncoAlert @NCRI_partners @Dukes_Club
@ASiTofficial
@me4_so
@YouESCP
@ESCP_studies
@escp_tweets
@EagleEscp
@EuroSurg
@Neil_J_Smart
@GianlucaPellino
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