Living Room 

CHINESE The Lung Cancer Living Room™ Immunotherapy Combinations Apr 17, 2018 Half hr Episode e

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[Music]good evening everyone welcome to theliving room thank you for comingeveryone in the room and everyone onlinewho might be joining us welcome welcomewelcome there are some new people in theroom tonight hopefully there's lots ofnew people online as well we're veryhappy to have you my name is DanielleHicks and my role here at the foundationis to oversee all of our patientprograms and services so anything thathas a patient touch is my area ofresponsibility of course with an amazingteam of people working with me to ensurethat this this program as well as manyothers go off without a hitch and arevery successful so we're very happy tohave you here tonight very happy to havedr. Jack West here from from SwedishMedical Center up in Seattle Jack is alongtime friend of the foundation andamazing medical oncologist and he'sgoing to talk about some really new andexciting things that that are literallyhot off the presses and and what it whatit might mean for you but what I'vedecided to do is rather than me try toread from a piece of paper or someone'sbio let them introduce themselves saywho they are and and why they chose lungcancer so with that and before we getinto the education part I'm going toturn it over to dr. West to introduceyourself thank you hi I'm Jack West realname Howard just lazy witness relocationand no but I grew up in Cleveland Ohioand between that and working in lungcancer it keeps keeps things real and soI really like to have it be casual I'm Itrained on the East Coast and then movedwell actually because I had grown up inCleveland and then was up in Boston formy training I was driving to work inJanuary and sliding all over the roadthinking it would be really nice to notrisk my life going to work every day andI decided I'd really like to be on thewest coast and came out to Seattle andtrained at Fred hutch for my fellowshipspecialty training in medical oncologyandhave been up there now for 20 years andthough there's a gravitational pull toCalifornia I'm still pretty happy withit rains in Seattle but I'm never gonnacomplain about the weather having comefrom where I have so anyway i'm ipractice now at Swedish Cancer Institutewhich is a large private center a verybig tertiary and quarternary carereferral center a lot of good lungcancer treatment and it's great that I'mpart of a solid team that works veryclosely together there I had done my Ifocused in lung cancer in my fellowshiptraining because I really wanted to workin a on a common cancer where there wassuch a need and I'll just say as ahistorical context that it's it'sastonishing how how far things have goneI know in the thick of it there's dailychallenges but it's so so different fromwhen I started in it people would askwhy did you choose lung cancer like youknow what's wrong with you it was it wasa hard field and when I was in myfellowship that the question that wasbeing asked in like the major journalsand conferences was is it actually doinganything to treat metastatic lung cancerare we moving the needle of thy givingchemo and it was just becomingestablished that giving chemotherapy didhelp people live longer but it was notso dramatic that you wouldn't ask thequestion and amazingly gratifyingly overthe last two decades it has changedincredibly so that now lung cancer is afield that is among the most dynamic inall of cancer care and I have I havefriends from medical school who are notoncologists who say they resent that theNew England Journal is just full ofcancer cancer cancer developments allthe time and my colleagues in othercancers are kind of jealous ofeverything that's happening in lungcancer it's it's dizzying it's like thefound money dream how quickly things arehappening in the fieldI've I it's it's hard to keep up and Ithink that's one of the themes that Iwould say about it's helpful to connectwith somebody who eats sleeps lives andbreathes lung cancer just because therehave been a lot of developments in manyother cancers you just can't keep upwith everythingand so that's but with that there's alot of new developments all the timeliterally the field has been changingeven based on presentations doneyesterday it's no exaggeration and therewas a big press release of some worklast week that I was thinking aboutdoing a video on I do some videos athome and put them out for people and Ithought there's no point in doing thatbecause even if I turn it around in 48or 72 hours I knew there was going to bebig news yesterday it would only have ashelf life of two or three days beforeit was obviated so it's a good problemto havethat's the highlights that's great so acouple couple things I want to point onthat you said Jack before before we movein is one of the one of the things ishow fast things are happening becauseyou've been in this face clearly engagedyeah way longer than I have I've been init since 2003 when you were diagnosedand and I've surrounded myself witheverything but you said something veryimportant it is changing so quicklywhich is why I we try to drive home inthis meeting and and throughouteverything we do why it's so importantto see a physician most patients areseen in the community setting right andthose of you who have been here and beencoming to this meeting for years some ofyou know that this is me beating thedead horse but community physiciansdon't have the luxury of being able tospecialize in any one job three Moore'sactually just to clarify I work in acommunity setting it is fair to say mostcommunity-based Doc's are not superspecial correct but you know in truththe it I would just say that you it'svery helpful to see somebody who isreally focused on thoracic oncologyright at least atEast sometimes and that's not to say youdon't actually have to get the treatmentby that person all the time the key truedes in whatever community is the samekey true des at the specialty center theantibiotics are the same so it's youdon't have to do everything you don'thave to get every infusion at a 90minute drive away so with that ok let'slet's get started on that ok so I'mgonna stand for this so I can refer abit to the slides but they are not thatdetailed and there's not it's it's notgonna be too much and so I'm gonna betalking as a very general introductionto the concept of immunotherapy and kindof where it's been historically which isnot ancient history it's really just inthe last few years where it is today andI should qualify that by literally todaynot tomorrow or next week because thatcould be different and the future wherewe're going and and this is I thinkyou're hearing the theme of very rapidlyevolving space we are still babes in thewoods learning about this and so but Ithink that one of the key themes is thishas been a big big field a big advanceit's not going to be the answer foreverybody but it has been a fundamentalchange and a big important tool for manypeople if not everybody ok next slide soI'm not going to go into much detailabout how the immunotherapy works theimmune system is very complex but whatis worth knowing is that like a lot ofcomplex systems in the body there is abalance where you don't want too muchand you don't want too little just likeclotting and bleeding I mean you don'twant to get a blood clot because yourblood tends to clot too easily when yousit down in the car for two hours butyou don't want to be bleeding all thetime for no good reason and there aremany factors that help control thatbalance and the immune systemis the same your immune system isdesigned to identify foreign threats andattack them when you have an infectionor cancer has some role in that becausepeople who have significant immunesuppression after say an organtransplant or a bone marrow transplanthave higher risks of developing certaincancers so the immune system does have asurveillance role trying to identifyvarious foreign things that includecancer but we don't want it to be sooverbearing that it's attackingbystander cells in your body and that'swhat autoimmune diseases are and thereare many everything from rheumatoidarthritis to ulcerative colitis vitiligovarious thyroid diseases lots ofdiseases in the whole world of ofillness are caused by the immune systemgetting confused and attacking your ownbody cells as an innocent bystanderand so the treatments that we have arelargely focused the ones we're going totalk about today are mostly at thebottom right of this and this is whathappens at the tumor level there is atumor cell which is the little blue andthen there's t-cells which are the whichare the muscle they are the the policeforce out there and they interact byrecognizing proteins on the cancer cellwhich is the little blue dot called apeptide that's just a recognized littlebit and then there's this interactionbetween receptors called PDL 1 or PDL 2and then PD 1 and they connect with eachother PD 1 is on the immune cell sideand PDL 1 is on the tumor side and theyconnect and shake hands and when thathappens it it actually is a is areassuring thing for the the tumor cellsays I belong here nothing to see heredon't you know I'm no threat to you it'skind of like the magnetbadge I used to to get into my clinicand but you can make counterfeits andthat's what the tumour does the tumourhas these ID badges that it doesn'tshouldn't have but that's what this PDLone protein is kind of like it's aprotein on the cancer cells that tellsthe it's an invisibility cloakessentially that tells the immune systemI belong here you know move on go on toyour business so we we've talked aboutthis PDL one you saw a kind of cartoonversion of it but it's just a proteinthat is on cancer cells sometimes notevery cancer cell not every tumor hascancer cells that have this protein somehave a lot on most or all of theircancer cells and some tumors have someon some of their cancer cells and somehave none anywhere and that's shown herethis is staining patterns what's itscalled a TPS or tumor proportion scoreof essentially zero we're less than 1%so it's just how what proportion of thecancer cells have this protein on itwhich stains brown this is onemagnification and this is a moredetailed magnification so you can moresee the outline of the individual cellsbut lots a little or none and sodifferent studies have included anythingfrom all of the patients across thespectrum to just focusing on thepatients with the highest level of theprotein to sometimes just some or a lotbut not including those with none it'sit's been everything in differentcompanies have had different prioritiesfor this it's about a third a third athird in proportion it's somewhere inthat range about 30% and about so it'sit's very close to a third a third athird as a basicand this PDL one is as I say just likethe security badge false sense ofreassurance and what we've generallyseen as a rule is that the patients whohave tumors with the highest level ofexpression have tended to be the oneswith the highest chance of respondingwell to immune therapies for the thelongest period of time let's move on sothe challenge is this is one of the bigbenefits of immune therapy is that youcan get dramatic and long-lastingresponses and in large part manypatients can feel great on this and haveno side effects the most common sideeffects we see are a little fatiguemaybe a rash or nothing at all butthere's no treatment for cancer that isrisk free and immune therapies nodifferent the immune side effects arejust very different from chemo and thoseare very different from targetedtherapies like Tarceva and the Alconhitters etc so they're different but theimmune therapies of which there areseveral drugs that we're gonna behearing about you'll see on TV etc allshare remarkably similar side effectprofiles and as I said most patientsthere they're mild but a minority ofpatients can have more serious sideeffects and they're the double-edgedsword of stimulating the immune systemit's the immune system attackingbystander parts of your body and theproblem is just about anything canhappenanything with an itis after itdermatitis colitis nephritis these areall just you know the words forinflammation of the skin inflammation ofthe lungs inflammation of the liverinflammation of the kidneys you can havejust about anything get inflamed fromyour immune system getting confused andgoing after a bystander soin Oregon but the liver the kidneys thecolon the lungs the thyroid variousother grande glands like the adrenalsthese are all things that can happen andthere's a very long list of 1% or lesspossibilities most of these are aboutone or two percent chance of being moresignificant but when you put them alltogether it's somewhere in the range of10 to 20 percent of patients need totake breaks from or stop immunetherapies because their immune system iscausing problems and I've had patientswho have to stop because they getinflammation in their lungs or theirkidneys are bothered by this and veryoften if you stop the treatment thatjust gradually gets better so this isthis is where things started publicationin 2015 a couple of them from work donein 2013 and 14 to different trials andthey are patients who have gotten priorchemotherapy and we're then moving on toa second treatment and the standardolder treatment regimen that is stillfda-approved and has a survival benefitis a drug called taxa tear or docetaxeland that was what we call the controlarm so half the people got that and halfthe people got Abdi veau also known asnivolumab and the trials wereessentially the same trial but sorry thenumbers there's a smaller number ofpeople people this should be one issquamous and one is non squamous I'msorry I copied that incorrectly butthey're essentially the same exactdesign just one group of people hadsquamous cancer which is about 20 or 25%of what's out there as non-small-celland the other group of patients had nonsquamous which is the other 75% or sothey they were otherwise the same studyand they both had the same results whichis that you had a clear survival benefitand a higher response rate and a longertimeuntil progression in and in general inthe patients who got opdivo and fewerside-effects taxa tear can be achallenging one and as I said thoughopdivo wasn't a freebie in terms ofside-effects it was easier and peoplelived longer and it was many monthslonger on average with some doing waybetter in fact I have a patient who ison one of these original trials who justis now five and a half years out with noevidence of her cancer and she was gonnago on Hospice if if this didn't work outhe or she couldn't get on the trial orif she progressed on it yeah she was notthis wasn't a slow process this was hercancer was pretty very lint and itstopped cold it got so much better thatshe came back a week later and said Ithink my pain is getting better and Ithought well that's the placebo effectcuz that's I don't think it's gonna workin a week but I'd like to say thatthat's the way most or all of mypatients did but unfortunately that'snot the case but it's exciting to knowwhat's possible let's move on so what weended up with was first opdivo and thenhe Trudeau studied a little after thatand then another drug called 2 centricor @s ilysm AB these are all similardrugs two of themopdivo and key Trudeau work as blockingPD one and two centric blocks the otherside of it PDL one but they had the sameresults essentially they all directlycompared to taxi tier in the same kindof populations and they all had asurvival benefit and very similar sideeffect profiles compared to each otherand they all got approved with slightlydifferent you know requirements two ofthem are AB Divo and two centric do nothave any requirement for any level ofPDL 1 and katroo de was initiallystudied in only PDL 1 positives andand where it was a beneficial treatmentand so it was approved just for that asa second line treatment so they all havevery similar efficacy I wrote 20 percentresponse rate or so 15-20 percent in thesecond line and that's the rate wherethe cancer shrinks significantly byabout half a lot of patients more than20% will benefit and that can be alittle bit of shrinkage or stabledisease when the cancer would otherwisebe growing and another thing that'sworth knowing about immune therapy isthat the scans are a little less helpfulor can be less helpful than they arewhen watching what they do on targetedtherapy or chemo where they shrink orthey grow and that's it with the immunetherapy there's a concept called pseudoprogression which is when the skin looksa little worse but the patient's doingbetter and it's not common and it's amistake to presume that every time yousee the scan look worse it's becauseyou're being faked out but it isimportant to see and incorporate how thepatient's actually doing because justtoday I saw a patient who had theirfirst scan looked maybe a little worsebut his pain was lessened he was gainingweight back after losing a lot of weightit just didn't fit and with furtherfollow-up I saw he just had a scan againhis second scan was a few weeks ago itwas way better and so you don't want tothrow out the baby with the bathwaterand so if if the scan and the person andtheir story don't fit give the patientthe benefit of the doubt and keep goingwhat you don't want to do is have thescan look worse the patient more in painand losing more weight and saying itmust be sued of progression let's keepgoing you don't want to just chase goodtime after bad I mean you've got perhapsother options but you don't want to justbeat on a bad treatment so just insummary several agents are alreadyapproved and previously treatedthey have appeared more similar thandifferent these are there are somedifferences but most of us feel thatthey are close to interchangeablecertainly as second line treatments theyhave staggeringly similar resultsthey're moving increasingly into thefirst line setting and we're stilllearning about which patients are bestserved by getting immune therapy as asingle drug first which should begetting it with chemo maybe somepatients getting it in combination withtwo immune therapy drugs but withgreater toxicity this is absolutely workin progress literally changing day today week to week and so that's greatbecause we're only improving we'resubbing out something that looks prettygoodfor something looking even better andthen this is moving from advanceddisease to earlier stage infants II nowapproved and only a couple of months agowas approved as a new treatment that isbecoming a standard for stage 3 lungcancer may translate to more peoplebeing cured of this and we are lookingat different ways to use these drugs inearlier stage patients before aftersurgery and then opdivo with or withoutyour voice being actively studied andincreasingly used in small cell andmesothelioma next slide and that's it sostay tuned because this is all happeningin real time[Applause][Music]

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