@TumorBoardTues 52 yo 🚺 w/ rectal bldg. Cscope: rectal tumor at 5 cm from anal verge; bx: adenocarcinoma. Scans with T3bN1 rectal primary, liver mets (dMMR). How to treat?
@TumorBoardTues Given KN-177 data (PFS, PFS2 advantage but no OS benefit to 1L pembro due to crossover), and CheckMate 142 data of nivo/ipi, we decided to give nivo/ipi after TB discussion. Thoughts on pembro vs nivo/ipi??
@TumorBoardTues So the plot thickens…after start of nivo/ipi, rectal tumor bx also sent for MMR testing by OSH and found to be pMMR! 🤔 (Liver was dMMR)
Do you routinely test two sites of disease (e.g., rectum and liver) for MMR/MSI?
Do you routinely test two sites of disease (e.g., rectum and liver) for MMR/MSI?
@TumorBoardTues Does this new info (pMMR in rectum and dMMR in liver) change your mgmt? What to do in 1L mCRC?
@TumorBoardTues So a pt update…after 2 cycles of nivo/ipi, CEA had normalized and scans showed improvement in liver AND rectum! Pt developed appendicitis, thyroiditis and adrenal insufficiency, however 😬😭
@TumorBoardTues Upon recovery (and appendectomy), pt underwent liver metastasectomy - of 5 original lesions, only 1 had viable cancer cells, and all had fibrosis!
@TumorBoardTues So after liver surgery recovery, obtained new scans…now cT2N+ rectal primary. We gave short course RT. Surgery ultimately showed ypT3N1b, MSS rectal primary. So now—adjuvant chemo or no?
@TumorBoardTues A few pts from this case, to review:
KEYNOTE-177 data at #ASCO21, #WorldGI2021:
Pembro vs chemo in 1L MSI-H mCRC
ORR 45.1% for pembro
PFS, PFS2 better with pembro
No OS benefit due to crossover
KEYNOTE-177 data at #ASCO21, #WorldGI2021:
Pembro vs chemo in 1L MSI-H mCRC
ORR 45.1% for pembro
PFS, PFS2 better with pembro
No OS benefit due to crossover
@TumorBoardTues CheckMate 142 results from #WorldGI2021:
Ph II nivo/ipi in 2L dMMR mCRC:
ORR 65%
mPFS, mOS not yet reached
Ph II nivo/ipi in 2L dMMR mCRC:
ORR 65%
mPFS, mOS not yet reached
@TumorBoardTues Discordance between MMR and MSI results: 1-10% (see Evrard, Cancers 2019, for review and study refs)
Reasons for discordance?
💡Low number of tumor cells
💡Lack of standard testing protocols, expertise in interpretation
💡Polymorphisms in ethnic groups
💡Tumor heterogeneity
Reasons for discordance?
💡Low number of tumor cells
💡Lack of standard testing protocols, expertise in interpretation
💡Polymorphisms in ethnic groups
💡Tumor heterogeneity
@TumorBoardTues And also: please test tumors in Lynch patients for MSI/MMR!
In an MSK study, 36% (37 of 103) of patients with Lynch syndrome had MSS tumors, and the majority (89.2%; 33 of 37) of MSS tumors from Lynch pts did not have dMMR signatures (Latham, JCO 2019)
In an MSK study, 36% (37 of 103) of patients with Lynch syndrome had MSS tumors, and the majority (89.2%; 33 of 37) of MSS tumors from Lynch pts did not have dMMR signatures (Latham, JCO 2019)
@TumorBoardTues And finally: a plug for our trial of nivo/ipi + SCRT for locally advanced MSI-H/dMMR rectal pts! 
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