Great #PrecisionDecision debate at #AACR18 with @VinayPrasadMD and @baslega1! Missed it? Who is ready for my first (and maybe only) TWEETORIAL? @AACR @sloan_kettering 1/15
But before I start, I have to admit that I was a bit intimidated to take on @VinayPrasadMD – the Twitter stats comparison wasn’t flattering. But I do have him beat on middle initials. #PrecisionDecision 2/15 
Ok, let’s get to it. First, we need to set the terms of the debate. Precision medicine is not a diagnostic test and it’s not an excuse for evidence-free off-label prescribing. #PrecisionDecision 3/15
Next, we need to define what constitutes a ‘match’ in genome-driven oncology. There are three components: tumor type, mutation, and drug. You must have all three. #PrecisionDecision 4/15
‘Actionability’ is also not a binary concept. There are multiple levels of evidence. For the purposes of this debate I’ll focus only on Levels 1, 2A, and 3A – where I think the evidence are[HD1] best. @OncoKB @CDebyaniPhD @gaojj @sloan_kettering #PrecisionDecision 5/15
We’ve analyzed data from ~23,000 samples sequenced by our FDA-authorized NGS assay MSK-IMPACT. ~15% had FDA/NCCN approved indications. Another ~10% have alterations with evidence of benefit from clinical trials. @MLadanyi @MFBerger1 @ahmetz #PrecisionDecision 6/15
As expected, the rate of actionability varies by cancer type with more than a dozen cancer types harboring tumor-specific approved indications. @OncoKB #PrecisionDecision 7/15
And we are continuing to make progress. Look at the evolution of indications over just the last 18 months! @OncoKB #PrecisionDecision 8/15
FDA approvals for genomically defined patient populations based on single-arm data have generally demonstrated response rates exceeding 50% combined with durability. Do we really think it’s ethical to randomize refractory patients to these therapies? #PrecisionDecision 9/15
Tumor-agnostic drug therapy has already upended established testing paradigms based around tumor types. In the cases of MSK-H and TRK-fusions, selective screening strategies based on enriched populations would miss ~50% of patients! #PrecisionDecision 10/15
Here I made some adjustments to one of @VinayPrasadMD editorials. The message: pivotal tumor-agnostic datasets closely mirror the distribution of the biomarker across cancer (ie: they are representative of how the drug would be used post-marketing). #PrecisionDecision 11/15
Like I said, Precision Medicine is not NGS. But while we are talking about NGS, it has lots of potential uses beyond ‘positive’ selection of targeted therapy. #PrecisionDecision 12/15
And let’s not forget where Precision Medicine has been used to achieve cures! #PrecisionDecision 13/15
Now @VinayPrasadMD has proposed this study to “test” Precision Medicine. Is that really what would be tested here? To me it looks like an effort to exclude all therapy we know actually works! #PrecisionDecision 14/15
So, what’s the conclusion here? Is Precision Medicine hype? Obviously not. But will it help everyone? Unfortunately not. As clinicians and scientists, we need to be responsible and constructive stewards of this important message. #PrecisionDecision 15/15
