@JackWestMD What do you think long term "cure" rate is with appropriately staged unresectable Stage III EGFR mutant disease? Sure looks like it is going to be in the 10-20% range we saw before PACIFIC.
@ManniMD1 @DrAdam_J_Bryant I’m spending less time on Twitter. Curious why you think quads are SOC for everyone now? Is there finally a OS or QOL endpoint from one of the studies, or is it the sheer volume of PFS and response data? I will grant that SOC shifts sometimes due to herd movement/expert opinion.
@n8pennell@LeciaSequist@TommyJohn00 I’m just not sure you would see different long term outcomes if you do good baseline staging and treat at MRD+ conversion. It’s not clear Osi is curing anyone even though there was an OS benefit in ADAURA.
@JackWestMD Is that SOC arm doing better than we would expect historically? Not sure I have seen updated limited stage KM curves lately and I generally expect worse outcomes. It makes the durva win even more impressive.
@Drjhoffmanmiami@MyelomaTeacher I’m MRD skeptical until we show we can use it to de-escalate or escalate treatments with better long term outcomes. I’m worried it will be used to approve financially and immunologically crippling combination therapies up front without a commitment to do the longer term studies.
@Drjhoffmanmiami@MyelomaTeacher But it can’t say if it improves long term QOL and OS. FCR had outstanding response rates and long term disease control options, but infections and side effects were major problems. I’m not convinced MRD is anything other than “molecular VGPR”, but it adds costs and pt toxicity.
@MyelomaTeacher What if toxicity and serious infections are much higher? Also, the duration of an MRD negative result is very short lived for some drugs (idacel). Maybe someday we will prove that we should change therapy based on longitudinal MRD assessments, but I don’t think that day is here.
@alex_epi_tria @GuiperiniMD If you are talking about new drug access, RR already gets drugs approved. If you are moving a drug to an earlier line, long term outcomes matter when many patients are doing reasonably well with existing therapies. Also, there are examples where MRD was higher, but OS lower.
@AJPortuguese@ManniMD1 But PFS does not automatically mean improved OS or QOL. Doublets are guaranteed decreased QOL from a side effect perspective and FFI (Freedom from infusion) perspective.
@AaronGoodman33 @Drjhoffmanmiami I think we need to push for enrollment payment transparency and “consulting fee payments” in informed consent, and ask non-conflicted expert groups to review and endorse trial design and proposed endpoints.
@AaronGoodman33 @Drjhoffmanmiami PIs have convinced themselves that any trial is OK as long as there is “informed consent,” and IRBs seem to lack the expertise and leverage to stand up to bad trial design.
@fabiopss @AaronGoodman33 Maybe consent forms need to include per enrollment trial fees that go to the investigator and the institution, and total renumeration from consulting fees with pharma. I fairly certain that these trials would be harder to run in US if pharma trial payments weren’t so generous.