Cancer In Lung

hello and welcome to identify with livevideo web chat series my name is melanie graham and today we're going to betalking with dr. jeffrey oxnard on the latest in lung cancer treatment andresearch it is lung cancer awareness month so we wanted to make sure that weget the latest information out to you doctor oxford is a physician with itoffers low center for thoracic oncology and he's also an assistant professor ofmedicine at harvard medical school if you have a question today for dr oxnardyou can submit it to us a couple of different ways you can email us at webbchapel at dfc i dot harvard edu or you can send it to us via twitter send ittoday if i restore handle using the

hashtag gfci web chats doctor also thankyou so much for joining us today so we want to kick it off just kind of withsome updates how has lung cancer treatment changed in the last five to 10years how our patients benefiting today more than they were a decade ago i thinkit's cool we cannot even talk about how much has changed in the past threemonths the idea that drugs are emerging at a rapid pace now and options arebeing created for lung cancer patients very exciting in 10 years ago a clinicaltrial would say doesn't matter what kimberly give to a lung cancer patientthey all the same outcome and clinical trials today are much more nuanced aboutfinding the right drug for the white

right patient lots of differenttreatment tools for our patients said that they even with stage 4 diseasewhich is generally incurable they can find a way to live for a long time withtheir cancer if they just find the right drug that that suits their cancer andgetting the right benefits i think there's a lot of optimism in lung cancerand lot of options for patients and a lot of clinical trials and a lot ofexcitement about but new things that might be coming patients always ask meyou know what's my prognosis doc and i say gosh lung cancer treatments changeso much today compared to a year ago or you for that that is even hard toestimate what we're gonna be doing in

the future and he just kinda sorta keepgoing and try to stay ahead of the science great so we're gonna get into alot of that new research and new treatments later on but one of thebiggest topics that sucks there right now is the idea that youdon't have to have smoked to get lung cancer i think there is a big stigma outthere that people talk about and that really the only risk factors that youhave to have lungs so we know that you know lung cancer screening cause issmoking but there are a large number of patients out there who have actuallynever smoked so do we know what drives their disease and you know how wedevelop treatments around that i think

part of the nihilism of ten years ago doesn't matter what you do for lungcancer same outcome was the idea that all lung cancer patients are the sameand what we've learned is back there's a lot of legend eighty within thatpopulation yes smoking is the risk factor the most common respect for lungcancer but i like to tell my patients you know i know what caused your lungcancer bad luck and that's true and that smoking is one way to get bad luck andmaybe there are other occupational exposures i can give you that bad luckor maybe it's just bad luck and we don't know and in some patients it can just bea simple genetic switch that can cause

lung cancer and i i hate to make itsound like it's out of your control except to say that we we can't pinpointa cause for everyone even when we get rid of smoking which we know is the mostimportant way to reduce lung cancer incidence worldwide's lung cancer stillgonna be out there lung cancer in non-smokers is itself theseven most common cancer worldwide and so this is its own problems and andappreciating that helps us recognize this hydrogen eighty and that in fact wemay have some kinds of therapies that are more more effective in the biologyof non smokers lung cancer and other therapies that may be more effective inthe browser smoker's lung cancer lung

cancer and so we we try to get at thisnuance in fact all my patients i try to quantify exactly how much they smokedand how long does it helps me get insight into possible differences in intheir underlying biology is their hereditary any kind of hereditary linkedwith lung cancer you know there are a lot of families outthere that have gotten lung cancer and multiple relatives the most common shared characteristic isthat all these relatives perhaps smoke cigarettes and so when you eliminatethat environmental cause is there an additional inherited risk that'sapparent aside from the props inherited

disposition smoking in the answer is yesthere are there are rare familial syndrome there's one that i study whereyou can actually have inherited egfr mutation egfr mutations will talk aboutit is the most common subtype of lung cancer are the most common geneticsubtype that we know to target but in terms of inherited risk there is areally rare inherited gene called each party 7 a.m. that can lead to lungcancer in non-smokers i don't think it's snowing your common enough that peopleshould be out there looking for it but its existence makes us think twice andmakes appreciate that there is more to lung cancer than just smoking in theremay be in fact inherited genes would

appreciate now we need to sort of takewhat we know about the genetic diversity of lung cancer and use that to revisitwhat causes lung cancer and maybe we'll find more of these inherited syndromesand so we have a couple trial then farber studying these families theserare families hoping to learn from them and learn things that we can applyotherwise perhaps non-smoking families with lung cancer so much and egfr yeahcan you talk a little bit about egfr maybe some of the other genes that mydrives some of these and these jeans when we talk about them primarilymeaning the cancer genes not the family's genes right these are cancergenes and they seem to be signatures

that lead to certain kinds of cancersthe the oldest signature we've known about its chaos chaos is a very commoncancer happens in colon cancer and pancreatic cancer we don't really havegreat targeted therapies for chaos the next most common the egfr we do havetargeted therapies for egfr and then over the past five years we'veidentified other less common but but very meaningful signatures that can leadto targeted therapies include alcon their alcohol is available ross rearrangements there rossinhibitors available met mutations are our recently discovered

rat erath her to the list goes on and onand in fact a number of the genes in this list are really only one percent oflung cancer and you think 1% lung cancer and how can that be meaningful but buteven 1% of lung cancer as thousands of people the united states and many morethousands around the world 1 percent of lung cancer is more commonthan some of the other cancer types out there and the problem is those 1percent's tend to blend in into the the total of the lung cancer and so one ofour our research priorities is finding those 1% identifying these individualsbecause if you add up all the 1% they add up to ten fifteen percent of lungcancer and that's a meaningful

population that needs are focusing needstargeted therapies to help them do better with their disease so tired ofthe next topic i want to go into what are some of the things that are on thehorizon what are some of the recent developments that are coming out forlet's first talk about the concert the targeted therapy chemotherapy is is a isthe older tool that we use in lung cancer chemotherapies effectively meanwe know chemotherapy can really work for a lot of cancer types has perhaps moretoxicities especially has cuba of toxicity is it can be hard to be onchemotherapy for a long time and it's not exactly a smart tool you can give itcross your fingers but there's not

really a biomarker to tell us who'sgonna work and was not targeted therapies can we actually think you'reout of biomarkers signature in the patient's cancer that makes themvulnerable to this smart drug perhaps milder more tolerable drug in the mostexciting of these are oral therapies pills you take once a day that hit at aninnate vulnerability of the cancer and can lead it to melt away reliably and i say reliably i meanyou're ninety percent of the time you have this vulnerability you get thespill and we see a dramatic benefit and so these pills therapies are now verycommon in our in our clinic practice for

egfr for our cross for beer after met inreally it's one of the fundamental second tools i tell my patients outthere's a variety of tools were gonna use for cancer one's gonna bechemotherapy one of those gonna be targeted therapy immunotherapy will talkabout down the line but if we can find a vulnerability connect you to a pilltherapy it's another strategy that can perhaps lead to durabledramatic benefit many parts of that is the idea of starting with one pill andgo to the next ones putting together targeted therapies against a certaintype of cancer this is this is done now and prostate cancer for example whereyou don't have just your first hormonal

therapy you now sequence togetherseveral hormonal therapies getting an underlying vulnerability and so workrecently doing this in lung cancer now too we have a number of 2 i'll contributorsand fda approved a person i now consider a second i now we have multiple egfrinhibitors that are approved and others that are now emerging so you can startwith a first drug and then get a second drug that sort of taxes certain kind ofresistance of the first drug using up the target approach before perhaps youneed to go back to chemotherapy ok so that actually answered my next questionis whether you can do these in

conjunction or is it one after anotherso could you do chemo and then targeted therapy do do them at the same time howdoes that work i think for a lot of patience we tried to check these geneticsignatures first so in my patients who first come in with metastatic non-smallamos non-small cell lung cancer all look for egfr look for outlook for ross thosethat the sort of the low-hanging fruit and if i find them within a shorttimeframe started pill therapy but it but if i cant find them i might turn tochemotherapy which is established regiment has a proven track record andwhile we're doing chemo dig deeper look for something else hoping that i canthen switch back to kill targeted

therapy as a second-line asian or maybeif i find something that i can't you second line even further down the linelook for clinical trial and so it in that way i'm going back and forth untilmy patients who are on an egfr inhibitor we need to switch to chemotherapy beforewe can find them something else and so these are tools that we use back andforth i think the important principals are the standard tools and those are thetools that are fda-approved we can use it in time and they are the clinicaltrials and clinical trials are bogus treatments that that fit into thatregiment at extra points and maybe get you an extra shot on goal to find agreat drug and so on my patients if i

could find them a clinical trial that'sexciting and they're eligible i generally say go for it because we canalways switch back to standard therapy later but this clinical trial made onlyfit your disease right now and we should take that advantage so we actually justgot a question in asking where it's a great point and so i say chemotherapytargeted therapy immunotherapy and local therapy of the full 24 tools i tell mypatients about 44 for their cancer in a patient with early-stage lung cancerjust one mass and lymph nodes local therapy like surgery and radiation is infact the most important part in a patient with metastatic disease withhave multiple sites disease local

therapy can't really cut it all out youneed to use local therapy sort of intelligent me for specific sites ofconcern and so will use radiation for brain metastases that's hard to controlwith chemo or bone metastases bothersome but it's true that local therapy is oneof our tools that we will fit into a patient's experience trying to fighttheir lung cancer over many years do you think that all cancer patients should betested for the standard of care today in lung cancer is that in patients with nonsquamous non-small cell lung cancer and lung cancer the most common type is nonsmall-cell small cells also the second type a little more aggressive innon-small-cell their squamous annonce

claimants those are sort of threesubtypes all of this genetic targeted therapy has been developed under nonsquamous non-small cell lung cancer and in that disease it is our standard ofcare to test for these difficult relations but the fact that we have madesuch a big impact in this subtype means that we're moving into these otherdiseases saying how can we find similar genetic signatures in squamous non-smallcell lung cancer and its small cell lung cancer so in fact there's a really bignational clinical trial trying to test for genetic alterations in squamousnon-small cell lung cancer this is nci national cancer institute run trialthrough the quarter groups and that is

called the lung mapper long masterprotocol trying to find genetic signatures and squamous lung cancer small cell lung cancer sort of catchingup a little bit we're still trying to learn about that i would say forstandard practice it's for non squamous but as part of research and hear danafarber we actually do genetic testing and everyone is partof a research protocol we try to characterize everyone's lung cancer to to learn about opportunities and thendevelop targeted therapies for those signatures that we find so let's shiftgears a little bit mentioned it a few

times that you know that he's really hottopic right now we had a lot of questions coming about it can you justtalk about some of the latest developments for lung cancer how theirproven treatment sure that the principle of using the immune system to attackcancer is an old one the probably the best established is iscalled stem cell transplant the idea of taking on your new system getting someof the new system and your body to to attack your leukemia and that is a verycomplex and and toxic therapy but is very effective in parts of oncologytrying to use the immune system in lung cancer has involved vaccine therapysometimes we've been trying a number of

different tools have been tried and it'sreally been decades of immune therapy research that is not really panned outfor lung cancer until suddenly we had these new class of drugs called immunecheckpoint inhibitors and these checkpoint inhibitors inhibit the immunesystem is is i think of it as the the tumor and immune system are alwaysinteracting in the immune system instead of sitting out tumor cells and immunesystem learns to use the signal to tell the immune system move on by ignore meyou know these are not the droids you're looking for and so it put on a littleflag called pdl one and if the immune system sees this plaque that says oh wecan't ignore that we can pass on by and

so not all tumors use this flag maybe 20or 30 percent maybe more use these signals to evade the immune system itthey'd immune surveillance that our bodies i was doing if we can block thatsignal immune system wakes up she's the cancer cell and can attack and wipe itout and so these are drugs like nivola mab embolism mad if you limit map whichare inhibitors of these checkpoints trying to help the immune system wake up see the cancer and and do what it'ssupposed to be doing now it doesn't work for everyone these drugs more maybe 20% of patientsare still trying to figure out who they

work best for it may work a little better and folkswho smoke cigarettes because it led leads to more complicated genetic typesof cancers we think versus in non-smokers lung cancer genetically moresimple and maybe the immune system isn't able to attack those as well we're stilllearning but they now become a new tool for our patients and so you know we tendto give it a try often after chemotherapy will try this because it'snot a sure bet but some patients can have very dramatic responses that canlast a long time and it's very rewarding to see in some of these patients whohave either cancer sort of melted away

some patients in fact you after a coupleyears being on a drug like this are now stopping and saying i take a break maybefrom here on in my immune system will do the job and i need treatment and that'sexciting idea i i would say that we haven't sorted out yet we now have a newset of options and and new excitement over how we can do even better and makeimmune therapy an option for everyone and so an enormous number of trials arenow being developed for a wide range of drugs and lung cancer trying to make a new one of ourfundamental tools on with chemo entire that there be so you mentioned this abit with smokers vs non-smokers are

there certain types of lung cancer alsonotable that work better immunotherapy seems to work better so asi talk about three subtypes non squamous non-small cell squamous non-small-cellon small cell therapies currently are available and fda approved for the twotypes of non-small cell squamous nuns claimants and are under investigationfor small cell lung cancer but but i think he will find that these drugs aregoing to try to find a toehold in every type of cancer you know they're being studied in therare earth rasa calamities like mesothelioma people are talking about iti moments or even the rarest disease are

now getting some attention trying tomake these drugs available for everyone is the goal so we got this caution infrom a viewer via email she says given the high recurrence ratesis there any kind of preventive immunotherapy for early-stage like stageone lung cancer so if somebody were to have surgery or something like that thatwould you go and immunotherapy just to prevent great question so we we talked about ourour for tools treating lung cancer and for early-stage lung cancer the stage tolung cancer lung mass and lymph node the essential tool first to surgery to getit out and then we used chemotherapy to

improve the curate that standard it'scalled adjuvant chemotherapy trying to eradicate any hidden cancer cells areleft behind but i presently don't use any targeted therapy in addition tosurgery and and chemotherapy that's different for example from breast cancerduring breast cancer you use surgery to use chemotherapy and then you might havea german targeted therapy like with trastuzumab herceptin and then add yourhormonal therapy after that and so we had these targeted therapies nowavailable why are we using these targeted therapies in cured or orpotentially cured patients to reduce the risk of recurrence like in breast cancerand so i'm actually one of the leads of

this trial called the alchemist trialanother nci national trial to look at a jan targeted therapies in resected lungcancer so the the trial's going to scream thousands of patients takingtheir tumor in testing first for those key to genetic alterations egfr now thatwe talked about in those patients that had huge fr or elk they're then eligiblefor target targeted therapy trials to try to improve the curate in somepatients at the gym for mutations after their surgery and chemo if they get itthey then are eligible to randomize to adjuvant erlotinib in egfr inhibitor fortwo years versus placebo no egfr inhibitor trying to say does targetedtherapy improved curates after surgery

chemotherapy for potentially curedearly-stage patients and there is now a new trial being developed added to thealchemist program to use adjuvant nivola map p1 inhibitor also asking whethertargeted therapy as an option for those who maybe don't have an egfr or alcoholduration so it's a great question and and you would think that now with allthese exciting targeted therapies we can make targeted there be an option forearly-stage patients were working on so another new kind of angle for treating we talked a little bit i don't know ifyou mentioned this before but you've been reading some clinical developmentin a technique that would find the

genetic abnormalities in patients tumorswith a simple blood test so can you just kind of how it's leading the way forhelping patients so we've talked about genetic signatures being so importanteven talk about how complicated this can be there and you have to get a biopsythat by just to be big enough to get the pathologist get the dna out of it andthen run that dna through a couple of tricks to find the alteration in andthat can take time it can take a week for some of the simpler ones can takeweeks and weeks for more complicated tests like next-generation sequencing inthat hunting for genetic signature is important but if we can make it easierand faster then perhaps we can connect

patients with targeted therapies moreeasily and so towards that goal we developed a blood test for the egfrmutations which are the most common signatures he said in the most importantat this point we involves looking not at the cells in the blood right you takethe cells that are you looking at just the free dna floating around most ofthat dna floating around in a lung cancer patients blood is the patient'sdna not the tumors dna but a subset of it maybe one percent of it is the tumorsdna and if you take that dna and sort of run through molecules one-by-one lookingat them you can count how many they were normal how many them or mutiny we have amachine machine now they can do this

cancer to sift through this haystacklooking for the needle that is the tumors dna and identifying a mutationthat belongs the tumor and so in a couple days on a blood test now we canfind these important mutations and therefore connect patients to targetedtherapy really quickly and easily without needing the process of a biopsyand and and the complexities of testing that in waiting around for the resultsthis is particularly important in the setting of resistance right on targetthere be four year to its working for you now have resistance the doc says ineed to know about your resistance let's get a new biopsy to figure out how yourtumors changed biopsy you know do i need

to gotta wait for the biopsy and itscomplications night await the results and instead put blood tests in two dayscan say we find this signature of resistance or not and that signature canlead to new territory so it's a really exciting strategy because it's it'sconvenient for patients and helps them get to target their peace faster andwe're working very hard to make it broadly available to sort of school fromtesting for the common stuff egfr and chaos genetic testing for everythingunder the sun to try to help as many patients as possible so you mentionedresistance that actually won a couple

questions asking about that whatresearch is being done to kind of work with patients who develop resistance totreatments are labs been saying that for a long time i think learning aboutresistance requires biopsies right figuring out what explains it requiresgetting you know having issues getting the nutrition saying what's changed andand that kind of research being done here over the past five years has led usto learn about the key signatures that can appear in egfr rican acquire a newt-seventy mutation or you can acquire met amplification or an alch where youcan acquire new app mutations that explain resistance and the same storiesbeing done in ross etcetera and so

there's a good track record of the textof using tumor tissue and using our laboratories to learn what explainsresistance their expressions when you figure out what explains it how youtreat it and it's an exciting story i think that's been going on here is is isfinding that drug to inhibit t-seventy m the most common resistance mutation inegfr and work that started five years ago in the lab of dr. union dr. danielgray here they said look and we develop a new kind of egfr inhibitor thatfocuses on hearing this t-seventy mutation and inhibiting the biology ofthe tumor without touching the patient's egfr inhibitor cancer without causingany side effects and it led to this

whole new class of drugs which are thesemutant specific third-generation egfr inhibitors which have really justtransformed our care of lung cancer and we expect to be asked to approve todayit's very exciting to think about how you a single by a single patient and some work in the lab leads to a drugwith these two trials which then feeds back and help those patients that's thewhole archive translational research here and it motivates us to do it moreand do it better and so there's a lot of abusing patient biology to lead to newdrugs that then treat resistance even better so i think we have excitementabout how to do that it's it's always a

problem though as soon as you have newdrug if patients develop resistance to the new drug and so it's a never-endingchase to to figure out what caused it and get the next drug ready for everyoneand the hope is that each of those drugs work long enough that patients can hangin there to benefit from the new drugs and emerged as we learn about whatexpect cause their resistance so we talked to a whole lot of new researchand new ideas that are coming out do you have any resources where patients canfind out about this read a little bit more about it oranything like that i mean we have you know what city farmer about precisionmedicine websites are talks a lot about

these targeted therapies in the new jackchanges to use we have a a patient forum coming up this saturday actually we'retalking about targeted therapies and that's going to be all day this saturdayhowever the process of living with lung cancer and about about patients are outthere and all around there are people out there who are doing this and livingwith this disease year after year i think i have to have some tools i tellmy patients as what you can do to do as well as possible and i three you threerules are living with lung cancer tell my patients which are don't act sick tryto keep doing stuff try to hang out with your grandkids and go out to dinner anddon't sit around if you sit around and

are are too sedentary you can get weakerreally good immobilize it try to hang on your strength i tell my patients don'tlose weight we aren't sure in lung cancer there is aperfect diet that helps you do better except calories weight loss is a problemand i tell my patients i like them to have 10 extra pounds for a rainy day andso patient you come see me i tell i'm going to go eat ice cream and try tomake sure that you have the calories you need to maintain your strength and mythird rules don't be a tough guy make sure that when you feel sick you callyour doctor and say you know i'm having a bad day

day i need to be seen any be taken careof because your ability to take care yourself you know it reflects are ableto take care of you that we can get you ready for the next thing there is anelement of planning an element of trying to stay ahead and keep on top of whatoptions are out there always ask about clinical trials always ask about what'sout there for me what are you gonna do next and what are you thinking about andand and that way we can anticipate where to go next year cancer and try to createoptions well thank you so much dr oxford thatwas fantastic a lot of great information a lot of good tips for patients outthere and thank you to our viewers for

tuning in today we really appreciate itand thank you for sending in your questions as well if you want to watch arecap of this chat or any of our other live web chats you can visit dana farberdot org / video web chats have a great afternoon