Welcome to The Lung Cancer Sessions brought to you by the Video Journal of Oncology (VJOncology).
This exclusive roundtable discussion features leading lung cancer experts Melissa Johnson (Sarah Cannon Research Institute, Nashville, TN), Lizza Hendriks (Maastrich University, Maastricht, Netherlands), and Heather Wakelee (Stanford University, Stanford, CA).
Watch this on-demand feature to learn about the exciting lung cancer advances from ASCO 2021 and gain exclusive insight into the use of immune checkpoint inhibitors in the adjuvant setting, including results from IMpower010, CTONG1103 & IMPACT, biomarkers of response, and new approaches.
IMpower010, CTONG1103 & IMPACT
“In the ALK patients, there’s not a hint of benefit with the atezolizumab. And that’s really important because a lot of those patients have high PD-L1. So it’s really important to, I always emphasize that whenever talking is, if you get a PD-L1 level back in a patient who you’re suspicious might have a driver, don’t start until you know what that driver is.”
– Heather Wakelee
“How do we move targeted therapies up into the adjuvant and the neoadjuvant setting? Is more always better and is earliest always better? Maybe not.”
– Melissa Johnson
CheckMate 816 & biomarkers in the adjuvant setting
“I think maybe one of the biggest messages is that we also need to start doing biomarker testing in early disease. You don’t want to give, especially your ALK-rearranged patient, but probably also not your EGFR, your ROS1 patient, immunotherapy. I think because in general results are not that good. Especially if you extrapolate the stage 3 and stage 4 data. And you know that you have significant toxicity if you give a TKI after immunotherapy in general. So you want to avoid immunotherapy if it’s not necessary in these patients.”
– Lizza Hendricks
Sotorasib and KRAS G12C
“And the reports from ASCO were on just over 120 patients, showing that the 960 milligram dosing, that the response rate was 37%. So, that’s encouraging. And to me, it makes it an absolute go-to medication for patients in second-line who have a KRAS G12C mutation in their tumors.”
– Heather Wakelee
“I think now you really need to raise awareness with your colleagues that are not following all new drugs, that also KRAS G12C is an option to target… And now you really need to be aware of what type of KRAS mutation a patient has and whether there is a clinical trial available”
– Lizza Hendricks
HER3 ADCs, EGFR exon 20 & more highlights
“We’ve treated a number of patients with patritumab deruxtecan at Sarah Cannon and have really seen some impressive responses. So, I’m cautiously optimistic about this agent”
– Melissa Johnson
“It’s definitely a very complex world in lung cancer with so many different agents looking into the same spaces, which is great because it means we can really pick the winners and be able to offer the best options for our patients.”
– Heather Wakelee
SECTION 1: IMpower010, CTONG1103 & IMPACT
Welcome to VJ Oncology’s post-ASCO discussions. We’ll be focusing today on the take-home lessons from the ASCO 2021 meeting, as they focus on the field of non-small cell lung cancer. I’m thrilled to introduce our panel today. First, I have Dr. Heather Wakelee, who is the Chief of the Division of Oncology at Stanford University. She’s the Deputy Director of the Stanford Cancer Institute. And as of September 2021, will be our IASLC President. I’m also joined by Dr. Lizza Hendriks, who is a pulmonologist specializing in lung cancer research at Maastricht University Medical Center. She is an Assistant Professor at the Research Institute, GROW School for Oncology and Developmental Biology. And just in 2021 has been appointed to the Young Academy at the Royal Netherlands Academy of Sciences.
So welcome to both of you. I am Melissa Johnson. I’m the director of the lung cancer research program at Sarah Cannon. We’re thrilled to have you all with us today. So let’s start with, it was a big ASCO all around, our second virtual meeting. Certainly, we’ve improved and made many strides over the last year, but Dr. Wakelee, could I ask you to kick us off with the discussion of the abstract that you presented as part of the oral abstract session about adjuvant atezolizumab.
Certainly. Thanks, Melissa. It’s great to be here and part of this discussion. So, the IMpower 010 study with the first Phase III adjuvant immune therapy trial to read out and the study randomized just over a thousand patients after they had had complete resection for early-stage lung cancer. They were enrolled and received chemotherapy, cisplatin-based doublet for up to four cycles and then randomized. So it was 1,005 patients to get a year of atezolizumab or just to be followed with best supportive care. And the study was designed to do hierarchical testing as we often do in these sorts of designs. And so the first population analyzed were patients whose tumors expressed PD-L1 and that ended up being about 55% of the patients and using that SP263 assays. So one of the tissue-based assays, tumor-based assays, and the stage 2 to 3A and that was 90% of the patients enrolled only 12% had 1B.
So when we look at the state 2 to 3A with PD-L1 expression, that first population, the disease-free survival hazard ratio was 0.66. So highly statistically significant and pretty exciting. So we also then looked at all comers with stage 2 to 3A and there it was statistically significant but that hazard ratio narrowed and it was 0.79. One of the exciting things, when we look at the curves, is patients only had a year of treatment but we have up to over 32 months now, and the curves are staying separated. We haven’t had enough events to have significance cross when we bring in that 1B patient population. So we don’t have anything final there, the trends look encouraging, but we don’t know. And same with overall survival. Way too early, at least some encouraging separation, but very, very early.
I think a couple of key points from the study are when we look at PD-L1 expression and how that influenced disease-free survival. When we looked at that all-comer stage 2, 3A, it was pretty clear with at least 1% expression 0.66, with greater than 50% expression 0.43 disease-free survival hazard ratio. But when we look at those who didn’t have any PD-L1 expression on their tumors, that disease-free survival hazard ratio was 0.97. So not significant. So there does seem to be that biomarker importance. The other thing we did on the study was we looked for EGFR and ALK in the patients with non-squamous histology. The study had about two thirds non-squamous, one third squamous. So for the squamous patients, we didn’t test EGFR and ALK and so they remain unknown and when you look at the kind of who went on the trial. But for the patients with non-squamous, they got tested and it was about 10% had EGFR, 3% ALK. In the ALK patients, there’s not a hint of benefit with the atezolizumab. And that’s really important because a lot of those patients have high PD-L1.
So it’s really important to, I always emphasize that whenever talking is, if you get a PD-L1 level back in a patient who you’re suspicious might have a driver, don’t start until you know what that driver is. And this reinforces that. The EGFR are stories a bit more complicated. In all-comers, nothing. In the EGFR patient, EGFR mutated tumors with PD-L1 expression, a hint of something. But I think that given the profound benefit with EGFRs TKIs in the setting, I wouldn’t act on that right now, but we’ll just have to see how things play out. So that probably a little more than you wanted to hear, but there’s so many different aspects of the study. So I always like to go into a few of those details. But really exciting disease-free survival hazard ratio for the patients with PD-L1 expression tumors.
Thanks, Heather. I might just ask a follow-up question. Have you found patients in your clinic to prescribe atezolizumab to already, are you starting to think about when you would apply this?
So I haven’t yet. But I’ve certainly been hearing some of our surrounding community physicians that they are and so that’s interesting because we of course don’t have the FDA approval yet. And it’s one of the unique aspects I think of being able to practice in the United States is that we do have these off label opportunities. And so people sometimes jump on data early for better or worse.
Lizza, let’s move to you and talk about another interesting abstract. That was not the first time that we’ve heard this abstract presented the CTONG 1103 trial, a Chinese multicenter trial. This was an updated analysis. Do you want to take us through that just briefly? Important given the abstract Heather presented?
Yeah, I think the key summary is that this was a randomized Phase II trial. So a smaller trial, including 72 patients with an activating EGFR mutation. Stage IIIA N2 disease pathology proven or FDG-PET positive, I think, and these patients received neoadjuvant therapy. They were randomized one-to-one to either anlotinib, a 150 milligram, once a day for six weeks or platinum-based doublet for two cycles. Then they were restaged and went to surgery if no progression. After surgery, they either received one year of adjuvant erlotinib or two cycles of platinum-based chemotherapy. Primary endpoint was response rate, and that was reported already. And it was significantly higher in those treated with erlotinib. And now what a long-term survival results were reported and progression-free survival. So the progression-free survival was also significantly longer for adjuvant or neoadjuvant erlotinib.
But I think around 21 months and 11 months for chemotherapy, but with long-term follow-up the overall survival was completely the same in both arms. And I think it couldn’t really identify a subgroup that really benefited from the EGFR TKI strategy. Maybe the elderly patients, maybe did a multilevel N2, but not really anything that would make you, I think, prescribe this outside of a clinical trial. And, also this is a randomized Phase II. I think what was interesting was that patients that progressed and received again, an EGFR TKI compared to those that progressed after chemotherapy and then received an EGFR TKI, the response rate in EGFR TKI were the same. So in this case, it doesn’t seem like that patients develop resistance after neoadjuvant and adjuvant EGFR TKI.
Yeah. It is an interesting juxtaposition with some of the other data that is emerging. Maybe I’ll just mention one last abstract, and then we’ll try to put all of these in context. And that is the IMPACT trial, which was a Japanese trial. Enrolled 234 patients between September 2011 and December 2015. So this is a trial with 71 months follow-up at this point, which strengthens the trial results, certainly. All patients in this trial, once again, had EGFR mutations and they were randomized after surgery to receive gefitinib 250 milligrams once a day for two years versus cisplatin-vinorelbine being typical adjutant chemotherapy at 80 milligrams per meter and 25 milligrams per meter day one to eight. And so while, initially, it did appear that patients who received the TKI were doing better and the median disease-free survival was 36 months for patients treated with gefitinib and 25 months, so 11 months between them, for patients treated with chemotherapy yet the hazard ratio over the lifetime of the trial was 0.92.
And the Kaplan-Meier curves showed that the lines went back together again after five years and they crossed at five years. So just like the data that Lizza presented, we see this question of how do we move targeted therapies, if you will, up into the adjuvant and the neoadjuvant setting? Is more always better and is earliest always better? Maybe not. I would say these second two abstracts suggest that it won’t be everybody that will benefit from an earliest strategy.
SECTION 2: CheckMate 816 & biomarkers in the adjuvant setting
Might I ask if either of you have comments also about the CheckMate 816 trial, of course, it was reported at AACR this year, chemo and immune therapy, nivolumab in this case, upfront for three cycles prior to resection and then surgical outcomes reported at ASCO. Any thoughts about this?
Well, I thought that the CheckMate 816 was really exciting data. Of course, we don’t have the patient relevant data, we have the surgical relevant data that’s been presented and it was encouraging. I mean, they had pretty high rates of pathological complete responses, 25% or so. A little outlier for earlier stage, but that was small numbers. And I think it was reassuring that if you looked at the surgical outcomes, they were actually better with the chemo plus immune therapy versus chemo alone. There had been some concern by bringing in that extra modality, there could be inflammation, it might impact the surgical outcomes, but it actually improved them. And so that’s really hopeful.
We’ve also seen a little bit about the toxicity and not too many surprises, but we really don’t know what does this mean then for disease-free survival for patients and ultimately overall survival as you were just highlighting is really what matters if we’re trying to cure patients, right? Just giving people more treatment early versus actually changing whether it cures them. These are slightly different questions. So I was encouraged by the data, but I think we need to see more before we know what it means.
I think that’s a, that’s an important theme that maybe all of this data together highlights, but there’s been a lot of discussions in the US, Lizza, I’ll be interested to know about in the Netherlands and in Europe, about which is better. CheckMate 816 or IMpower 010. What are you going to do? And, I think, Heather makes a really good point that we’re comparing apples and oranges a little but still until we have this later data, like the Tada and the Wu abstracts, Japanese and Chinese abstract showed us. What are your colleagues saying in Europe?
I think in the Netherlands, we also have quite some discussion on how to proceed. In the end, I think you need biomarkers, but I think at the moment it’s very difficult because usually in early stage you have a small biopsy before you proceed to a resection and nothing more. And you need to also be quick to start treating the patients. I think there was discussion ongoing on chemo-IO compared to IO neoadjuvant. And in general, you will have better results with chemo-IO, but you also want to identify those that are having enough with only immunotherapy. And I think the big advantage of neoadjuvant therapy is that you will have the tissue, that you will have your outcome on immunotherapy and chemotherapy and your hope that it will be associated with long-term disease-free survival and overall survival. So it’s a bigger opportunity for biomarker research.
I think it’s easier to give adjuvant therapy, but patient selection, again, as Heather also indicated plays a role. And I think maybe one of the biggest messages is that we also need to start doing biomarker testing in early disease. You don’t want to give, especially your ALK rearranged patient, but probably also not your EGFR, your ROS1 patient immunotherapy, I think because in general results are not that good. Especially if you extrapolate the stage 3 and stage 4 data. And you know that you have significant toxicity if you give a TKI after immunotherapy in general. So you want to avoid immunotherapy if it’s not necessary in these patients.
Yeah. I think that’s really well said and does in a way that I hadn’t thought of add support to the importance of the biomarker testing in the adjuvant setting. Before we leave this topic, Heather, at Stanford, tell us what the state-of-the-art is for biomarker testing in the adjuvant setting right now? Have you been able to convince your health systems to let you do that?
So we are testing and part of it is we’ve been participating in the ALCHEMIST study. And so, we’d gotten into a role with always looking for EGFR and ALK and then for PD-L1 as part of that bigger study and ALCHEMIST of course, had stopped for the EGFR component after ADAURA But patients are still being followed for that. The ALK portion of that is still ongoing. And I think that we still don’t know what’s going to be the best adjuvant treatment for an ALK patient, and if we can extrapolate, right? So there’s still key questions, but we’re able to do that. We’re also able to test our stage 3 unresectable patients and what our biggest research effort that’s ongoing right now is actually looking at that MRD, the minimal residual disease, if there is any and testing patients for that using our platform and then deciding to give additional treatment based on that or not.
Because I think that what we really need to be looking at is how do we give all the treatment needed to try to cure patients, but no extra, right? Because as we bring in treatment and even with, oh, I know, I mean, definitely there’s toxicity. When you give a checkpoint inhibitor, some patients end up with pretty significant autoimmune problems and that’s true, whether it’s metastatic or early stage or whatever cancer it is. And so we don’t want to be giving everybody those drugs if they’re not going to help, because the toxicity doesn’t care, whether or not your tumor responds. It’s just they’re separate biomarkers and so I think those are the big questions that we need to really address is how do we give all the treatment needed to the right patients and none of the extra treatment? And I think that MRD is going to play a big role there.
I agree. MRD is a very promising new addition to the testing. Lizza, what about you? What kind of biomarker testing are you able to do in the adjuvant setting and what about struggles or challenges in the neoadjuvant setting right now?
I think in general, in the Netherlands, it’s not in the guidelines. There is no formal reimbursement. So yeah, we select patients for biomarker testing. So if you now have a never or a light smoker or a very young patient, you do it. But if you do it for every patient, you have a financial problem. And in the Netherlands, you cannot prescribe, for example, adjuvant immunotherapy already after a surgery because it’s not approved, not reimbursed. So it’s just not possible, but I think we are moving and we are negotiating now to have biomarker testing for all of these patients. And preferably clinical trial, I think with all these results, with the CheckMate, with the IMpower, with the ADAURA I think if you have a clinical trial, you have very convincing results to ask the patient to participate in another clinical trial. For example, with MRD, which we have now.
Yeah. That’s well said, certainly in the adjuvant setting where the goal is cure, that’s a great goal for all patients and all doctors.
SECTION 3: Sotorasib and KRAS G12C
Well, let’s switch gears then and spend a little bit of time talking about some of the other interesting therapies of note from ASCO 2021. In some ways, just like in 2020, when we saw a couple FDA approvals right before ASCO, that was also born out at this year’s meeting. So I won’t steal your thunder the way the FDA did ASCO’s. Heather, why don’t you talk about the Skoulidis paper?
So, that is with the sotorasib. So the first KRAS inhibitor ever approved. All the ones currently in development, well, believe one’s in development, it’s focused on the G12C with that C, the cystine, being really important part of the way that the drug works as far as forming those bonds. And that’s what made the undruggable somewhat druggable, at least for that patient population. And the reports from ASCO were on just over 120 patients, showing it that the 960 milligram dosing that the response rate was 37%. And so we’d seen response numbers kind of flip around a little bit and with small numbers of patients. But now I think that’s probably a pretty good number to put in mind as to about the likelihood of response and the duration of response was around 11 months. And so that also was a little longer than what we’ve heard about in some of the earlier reports.
So, that’s encouraging. And to me, it makes it an absolute go-to medication for patients in second line who have a KRAS G12C mutation in their tumors. They also followed up on some data that had come out earlier too, with the co-mutation questions. So STK11 and KEAP1. KEAP1 continues to be a bad actor, but even with a KEAP1 mutation, numbers are small. But it was 20% response to the drug and so with sotorasib, so it doesn’t mean I wouldn’t use it just, I would be less enthusiastic about it. And then with STK11, even though that’s been a bad actor with chemo and immune therapy in a lot of reports, at least in this presentation and follow up to earlier work as well, it didn’t seem to be a negative actor. So if you have KRAS G12C and you have STK11 mutations in the tumor, those patients, if anything, did better than if they didn’t have the STK11, certainly not worse.
And so that was encouraging to see because STK11, were we trying to make sense of that as well. So it was exciting and I think certainly warrants the approval and now all the questions are around, well, when would we use it first-line? What else should we give second line? I think, but to me, it’s my second line go-to drug now for my patients with KRA G12C.
Yeah. I think it is exciting for all the reasons that you mentioned, but just in the world that we live in, where the standard for so many, especially with tumors without high levels of PD-L1 is chemo immunotherapy, three drugs, typically it’s a formidable challenge to figure out how to find a niche in the frontline. And, is that a monotherapy strategy? Is that a combination strategy? And if so, with what? Lizza, have you had discussions about KRAS G12C positive patients before second line before? Do you think it’s feasible to find these patients in the frontline before they get chemo immunotherapy in your practice?
Yeah, I think in the Netherlands, it’s usual to do next-generation sequencing PD-L1 before you start your first-line treatment. So, you know whether the patient has a KRAS G12C. Again, in the Netherlands, not reimbursed, not approved, so we cannot just prescribe it. But trials also in first-line are ongoing. And, I think now you really need to raise awareness with your colleagues that are not following all new drugs, that also KRAS G12C is an option to target. I think for years, we always stayed at KRAS, yeah. Nothing to target chemo, chemo-immuno, whatever. And now you really need to be aware of what type of KRAS mutation a patient has and whether there is a clinical trial available. And also, we have, now, second line trials ongoing. You really need to refer patients, I think for clinical trial, especially if you progress after chemo immunotherapy. Standard option is, I think docetaxel whether the poor response rate, poor overall survival, poor progression-free survival. So you really should give your patient a chance and see whether something is available.
I think the most interesting thing about this more mature data set with sotorasib was, to me, the duration of response of 11 months, because anytime you have an oral therapy that you’re giving daily with reports of nausea, GI side effects, diarrhea, even some creatinine elevation, as we’ve seen with this and other direct KRAS G12C inhibitors, the amount of time that you can give that drug is sometimes, the devil’s in the details there. That if you can only do it for six weeks, it’s not a tenable strategy. So many times when we’ve tried to target KRAS in the past with other inhibitors in the MAP kinase pathway, they’re just not tolerable. So to me, watching the duration of response of as it matures for sotorasib and also adagrasib made by Mirati, that’s a fast follower perhaps to approval will be very interesting.
I’ve also thought it was interesting that people have shown up at Sarah Cannon for trials, with a KRAS mutation with sotorasib written on a piece of paper because their doctor has heard about it and they’re wanting it. But they’ll have a KRAS G12D mutation, or a KRAS G12B mutation. So we’ve found that there’s a heightened awareness, but also I think a heightened awareness on the part of pharma biotech, as we’ve seen an increase in the number of therapeutic options in trials. Heather, you’re nodding. Have you seen that as well or other comments?
Well, I think the other KRAS mutations definitely remain a challenge. So we have a investigator-initiated study that we’re doing, I wanted to mention too, with Lung-MAP. So within the US cooperative group network, there is a study combining sotorasib with other compounds when there are specific co-mutations that might be resistance mutations. So I think this is really exciting, but we’re not done. So there’s still a lot of research that needs to keep happening. And I agree that it’s really amazing that we can offer something to some patients with KRAS mutations, but we still have a lot of big questions to answer.
That might be a good time to transition because that sums it up really nicely.
SECTION 4: HER3 ADCs, EGFR exon 20 & more highlights
Let’s talk a little bit more about some of the other targeted approaches that showed promise. Pasi Janne reported patritumab deruxtecan’s experience, which of course is HER3-directed antibody-drug conjugate made by Daiichi Sankyo. In this trial, he reported an experience of 81 patients all with a non-squamous non-small cell lung cancer, all with EGFR mutations. The majority of patients had previously been treated with osimertinib and platinum. So this was the unmet need of acquired resistance to osimertinib which is a relatively new field after the FLORA data changed the standard of care a few years ago. The response rate that Dr. Janne reported was 40 or 39%, I should say, PFS 8.2 months with a duration of response of seven months. Again, speaking to the well tolerated nature of this antibody-drug conjugate that’s given once every three weeks IV. I think the coolest part of this analysis was the slide that showed all of the mechanisms of resistance of patients coming into the trial right below their little position on the waterfall plot.
Majority of patients had some disease response, and then we saw it didn’t matter what their mechanism of resistance was. If it was EGFR-driven still like C797S for example, was it non EGFR-driven like KRAS, BRAF, HER2. Was it an amplification of a gene? Like EGFR once again, like CCNE1, all of these we’re used to seeing when we profile these patients after osimertinib resistance. And to have an option for all of them with a response rate of 40% seemed pretty good. The only criticism perhaps of this abstract that I’ve heard is just that the responses didn’t correlate so well with HER3 expression within the tumor. And so while we hypothesized the way this drug works is by seeking out HER3, there wasn’t a crisp correlation in the data presented.
And so I think there’s more to come here. We’ve treated a number of patients with this drug at Sarah Cannon and have really seen some impressive responses. So, I’m cautiously optimistic about this agent. Lizza, let’s pass the ball to you now. Tell us a little bit about, this was a big year for EGFR exon 20, a very tiny little subset of patients in lung cancer. Tell us about some of the work that was presented.
I think for the last couple of years, we didn’t have much therapy for these patients, so for the first/second generation EFGR TKI were tried. And I think we’re quite disappointing, also osimertinib where sometimes maybe double dose, but in general response rates and progression-free survival quite low. And now we’re seeing to getting more and more options. At ASCO, the mobocertinib EXCLAIM data were presented. So this was a Phase I/II study with expansion and extension cohorts and the platinum pretreated extension and expansion cohorts were presented with just over 100 patients. So an update and response rates are not what you see with the classical EGFR mutations, but 25, 28%. But with a median progression-free survival of over seven months. And I think a very interesting duration of response. So that response very well with 17 and half months were quite interesting. I think, but can be a problem with this drug.
We discussed our ability and this drug has quite some nausea, vomiting, diarrhea, skin problems. So quite often dose reductions are necessary. And it seems that those managements are updated with a better supportive care, but still, I think this is not an easy drug to give. What you hope also with, with EGFR TKI, also for EFGR exon 20 that you have brain penetration and efficacy in the brain. But this drug, first side of progression was quite often the brain and those with baseline brain metastases didn’t do that well. So I think he has really an unmet need for EGFR exon 20 to also have drugs that work in the brain. And we have more options. We have amivantamab. So an EFGR-MET antibody. Response rates are, I think, in the range, maybe a little bit above the mobocertinib data. But small numbers of patients are difficult to compare. But really different toxicity, maybe a fusion reactions, rash compared to the gastrointestinal side effects of mobocertinib. progression-free survival I think similar.
Osimertinib, maybe a little bit less impressive response rates, 14, 15%, and also again, quite significant toxicity, but there was a poster presentation where it was shown that it has some brain activity. So maybe this could be a position for osimertinib. And also a new, exon 20 inhibitor. These are the DZD9008, Phase I, low number of patients. But also I think a quite interesting response rate and maybe a little bit less toxicity. So I think we should watch this space and again, test for these patients. And, also I think check your patients that are living long. Usually these patients don’t live long, but really check whether you have patients where you missed the exon 20 mutation and see whether something available.
I just met a patient with an EGFR exon 20 insertion yesterday, and she had read about amivantamab already and said, “Why can’t I skip the chemo and get this first?” And I sort of thought about it and decided that it probably wouldn’t be a good idea. I probably wouldn’t be able to get it covered. But do you think, Lizza, that these drugs will be strong enough to make the slide into that front-line setting for this subset of patients as well?
I think in, in mono therapy… I think not. You would like to have a higher response rate, longer progression-free survival. So, I mean, for amivantamab, you have to PAPILLON trial that’s ongoing, amivantamab is playing with like surplus carboplatin compared with pemetrexed-carboplatin alone. So I think it’s an interesting option. To be honest, I would have liked to see chemo-IO maybe as the comparitor. We know that immunotherapy monotherapy doesn’t work in these patients. But may be a combination could work, but unfortunately that was not tested. I think also with regulatory problems, otherwise… Mobocertinib is being evaluated against chemotherapy. So we will have data and it will be interesting to see these data, but I think for now it is not strong enough to move to first-line.
Yeah. But I think an interesting growth or progress, nonetheless.
You also see these drugs that all… Two were classic TKIs, perhaps one with great brain penetration, but also this bi-specific antibody, amivantimab being an EGFR-MET bi-specific, seeing some new mechanisms of action that patritumab deruxtecan as well in lung cancer, to me, was an exciting sort of glimmer of sunshine that we’re moving into some new spaces. Who knows what will be coming. Where there other little glimmers of sunshine, or maybe not specific abstracts, or maybe so that you will take away from ASCO 2021? Maybe I’ll start with Heather.
I think we’ve really talked about some of the most exciting developments. It’s definitely a very complex world in lung cancer with so many different agents looking into the same spaces, which is great because it means we can really pick the winners and be able to offer the best options for our patients. We’re still frustrated by resistance. Tumors remain very clever and so just trying to… I think for me, I very much applaud all the work being done in understanding when the drugs are working, why and when they stop working, why so that we can really have more informed choices to offer our patients as we continue to understand more and more and move into the future. So there was a lot of that that I was also looking at and found pretty intriguing.
Thank you. And Lizza, what about you?
Maybe to add, we talk about biomarker testing new drugs, but there was also a presentation that quite a lot of patients don’t receive all the testing. So even the targets where you have approved drugs are not being tested in all patients or are not being tested before starting first-line. I think this is a very strong message also really to have biopsy even a liquid biopsy and test your patient because it really matters for the patient.
Yeah. I agree with you. That was maybe not a ray of sunshine, but a reality. I think that speaks not just to… I think the medical oncologists know, but it’s getting enough tissue and it’s understanding from the perspective of the payers across the world. That we need this testing to be reimbursed at diagnosis and not as patients go along. There are so many aspects of this problem that I would love to unpack because I think it is much more deep seated than just a knowledge gap amongst our colleagues. One other thing that I will take away from this year’s ASCO was the amount of ctDNA work across many tumor types or across many subtypes of lung cancer, I mean to say. And how you can use the disappearance of ctDNA clones to track how your patients are doing, similar to what Heather talked about with respect to MRD status in the adjuvant setting.
I think that there is a lot more that we can learn from the blood and that since that’s so much easier to access than tissue, I have been using blood testing for a long time, just from its practical advantages and was glad to see that. All right, well, I think we’re almost at the end of our time today. I just want to thank Heather and Lizza for their discussions. It was a great discussion. I hope you enjoyed it. Thank you for joining us and see you in ASCO 2022.
Recording date: 30-June-2021; Webinar broadcast date: 21-July-2021; Feature publication date: 22-July-2021.
Consulting or Advisory fees received from:
Otsuka, Astellas Pharma, Genentech/Roche, Boehringer Ingelheim, AstraZeneca, Calithera Biosciences, Merck, Loxo, Sanofi, Mirati Therapeutics, Pfizer, Guardant Health, Ribon Therapeutics, Incyte, Abbvie, Achilles Therapeutics, Atreca, GlaxoSmithKline, Gritstone Oncology, Janssen Oncology, Lilly, Novartis, Association of Community Cancer Centers (ACCC), Amgen, Bristol-Myers Squibb, Daiichi Sankyo, EMD Serono, G1 Therapeutics, WindMIL, Checkpoint Therapeutics & Eisai
Received research funding from:
EMD Serono, Kadmon, Janssen, Mirati Therapeutics, Genmab, Pfizer, AstraZeneca, Stem CentRx, Novartis, Checkpoint Therapeutics, Array BioPharma, Regeneron, Merck, Hengrui Pharmaceutical, Lycera, BeiGene, Tarveda Therapeutics, Loxo, Abbvie, Boehringer Ingelheim, Guardant Health, Daiichi Sankyo, Sanofi, CytomX Therapeutics, Dynavax, Corvus Pharmaceuticals, Incyte, Genocea Biosciences, Gritstone Oncology, Amgen, Genentech/Roche, Adaptimmune, Syndax, Neovia Oncology, Acerta Pharma, Takeda, Shattuck Labs, GlaxoSmithKline, Apexigen, Atreca, OncoMed, Lilly, Immunocore, Jounce Therapeutics, University of Michigan, WindMIL, TCR2 Therapeutics, Arcus Biosciences, Ribon Therapeutics, BerGenBio, Calithera Biosciences, Tmunity Therapeutics, Inc., Seven and Eight Biopharmaceuticals, Rubius Therapeutics, Curis, Silicon Therapeutics, Dracen, PMV Pharma & Artios
Received travel, accommodations and expenses from:
Abbvie, AstraZeneca, Genentech, Incyte, Merck, Pfizer & Sanofi
Received grants/contracts from:
ACEA Biosciences, Arrys Therapeutics, AstraZeneca/Medimmune, BMS, Celgene, Clovis Oncology, Exelixis, Genentech/Roche, Gilead, Merck, Novartis, Pharmacyclics, Sea Gen, Xcovery
Advisory board for:
AstraZeneca, Xcovery, Janssen, Daiichi Sankyo, Blueprint, Mirati, Helsinn, Merck, Genentech/Roche
Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid:
Roche Genentech, Boehringer Ingelheim, AstraZeneca
Boehringer, BMS, Eli Lilly, Roche Genentech, Pfizer, Takeda, MSD, Amgen
Roche Genentech, AstraZeneca, Quadia, Roche Genetech
Local PI of clinical trials:
AstraZeneca, Novartis, BMS, MSD /Merck, GSK, Takeda, Blueprint Medicines, Roche Genentech, Janssen Pharmaceuticals, Mirati
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