What are your top takeaways in GI Cancers from ASCO 2023?

It was a big year for rectal cancer treatment!

1. PROSPECT (Deb Schrag et al.,) - for selected “high” rectal cancers we can likely omit radiation if they have a good response to FOLFOX. Notable exceptions: tumors that require an APR, are stage T4 or N2. About 10% of patients will not have at least a 20% response to FOLFOX and will also need radiation.
2. FOWARC (Zhang et al.,) confirmed these findings in a randomized trial in China with updated survival data presented at the ASCO Annual Meeting this y...

1. PROSPECT study: This study enrolled 1,194 locally advanced rectal cancer patients (main inclusion criteria: ECOG 0-2, age >=18, T2N+ or T3N+/-, eligible for sphincter preserve surgery at initial diagnosis, tumor is not within 3 mm of the radial margin). There, patients were randomized 1:1 to two arms. Patients in the experimental arm started with FOLFOX for 6 cycles, if the primary tumor decreased in size by at least 20% at restaging, then these patients will go directly to TME surgery and then...

1. PROSPECT: phase III study of neoadjuvant chemoradiation vs neoadjuvant FOLFOX CT with or without chemoradiation for patients with locally advanced rectal cancer (abstract LBA2).
2. NORPACT-1: randomized phase II study of short-course neoadjuvant FOLFIRINOX vs upfront surgery for patients with resectable pancreatic head cancer. There is significant interest in using a neoadjuvant approach to improve outcomes for people with pancreatic cancer and in a number of centers such an approach is now routin...

1. PROSPECT: A randomized phase III trial of neoadjuvant chemoradiation versus neoadjuvant FOLFOX chemotherapy with selective use of chemoradiation, followed by total mesorectal excision (TME) for treatment of locally advanced rectal cancer (LARC) (Alliance N1048).
   This study was simultaneously presented and published in NEJM. Nearly 1,200 patients were randomized to standard of preoperative long course chemoradiation followed by TME vs 6-8 cycles of XELOX/FOLFOX chemotherapy alone followed by TME....

1. PROSPECT: In patients with locally advanced rectal cancer that were also eligible for sphincter sparing surgery, neoadjuvant FOLFOX with selective use of 5FU CRT was non inferior to 5FU CRT with regards to DFS. This randomized phase 3 trial is practice-changing and empowers patients by giving them options for achieving a high cure rate.
2. HERIZON-BTC-01: The HER2 bispecific antibody zanidatamab shows encouraging, durable, and rapid responses (ORR 41%, DOR 12.9 months, time to first response 1.8 m...

1. Clearly, the most impactful trial was the PROSPECT trial. Coupled with the increasing amount of data showing that some patients with locally advanced rectal cancer can successfully be treated without surgery (the so-called "watch and wait" approach), this demonstrates that we are now able to offer a certain subset of rectal cancer patients an approach where we attempt to leave out one of the three standard components of therapy. Everyone will need chemo, but some patients may not need radiation...