Welcome to The GI Cancer Sessions brought to you by the Video Journal of Oncology (VJOncology).
This exclusive discussion features leading experts Lizzy Smyth, Yelena Janjigian and Zev Wainberg, who offer their perspectives on the key data and highlights in upper gastrointestinal cancer from the ESMO 2021 Annual Meeting.
In gastric cancer, the experts discuss the potential of CLDN 18.2-targeted CAR-T, CheckMate 849 and the OS benefit of 1st line nivolumab plus chemotherapy, as well as T-DXd in DESTINY-Gastric02. They also dissect the MAHOGANY data and consider the potential of chemo-free regimen in HER2+ gastric cancer. The panel also discuss data from KRYSTAL-1 evaluating adagrasib in KRASG12C-mutated colorectal cancer and PRODIGE 24, which compared adjuvant mFOLFIRINOX and chemotherapy with gemcitabine in patients with resected pancreatic adenocarcinoma.
On CLDN18.2 CAR-T:“It’s a unique target ’cause in some respects there’s not a lot of claudin activity outside of the normal stomach mucosa. So in some ways it lends itself to these sort of CAR-T ADC strategies, which I think are, you know, really exciting to see some efficacy in solid tumors. I can’t think of too many other examples in GI malignancies where we’ve actually seen responses with CAR-Ts that are like this. So I think there might be something to this.”
– Zev Wainberg
CheckMate 649 + DESTINY-Gastric02
On CheckMate 649: “And with two-year follow-up, we did see more complete responses on the NIVO plus chemo, so that was interesting. The other kind of, you know, notable fact about the new IPI arm is that overall response rate with MSI-high population was 70%. And as we know with NIVO/IPI, if you do respond even in MSS patients, their duration of response is nearly doubled with addition of, with dual checkpoint inhibitors in first-line setting. The overall response rate with NIVO/IPI was 26% in first-line, which is very interesting, right? ‘Cause it’s almost the exact same overall response rate in third and fourth-line.”
– Yelena Janjigian
MAHOGANY & chemo-free regimen in HER2+ gastric cancer
“We’re in a good situation where we can even discuss this, bear in mind that’s also a double selective population, PD-L1-positive, HER2-positive. I think what I would like to see is, you know, questions asked in future by sequencing. So chemo-free followed by chemo. How does that equate with everything upfront? I don’t know, I mean, that sounds very much like an academic study to me rather than an industry study, but I think these are questions that we can ask in future.”
– Lizzy Smyth
PRODIGE 24 in PDAC
“Our friends in pancreas cancer, unfortunately, are not quite as fortunate, neither with respect to new drug development, nor with respect to any immunotherapy combinations. But we did see at ESMO 2021 long-term data from the PRODIGE 24, and I think, you know, reassuringly, what you want to see in a long-term dataset like this is that the five-year survival holds up. And it certainly does.”
– Zev Wainberg
Watch Full Video
Read Full Transcript
SECTION 1: KRYSTAL-1 & CLDN18.2 CAR-T
Hello, everybody, I’m Dr. Lizzy Smyth. I’m here today for the GI sessions of VJOncology post-ESMO Review. I’m here with Yelena Janjigian from Memorial Sloan Kettering Center, New York, and Zev Wainberg from UCLA. Welcome both.
Yelena Janjigian: Thanks for having us.
Zev Wainberg: Hi.
Lizzy Smyth: Great to see, so Yelena, in your opinion, what were the biggest GI outputs from ESMO this year?
Yelena Janjigian: Yeah, ESMO 2021 was a great opportunity to come back. And some of us attended in person, I would say in colorectal, in the presidential session, KRYSTAL-1 really made an impact. Adagrasib is an inhibitor that looked at, in the study KRYSTAL-1, we looked at monotherapy or in combination with cetuximab in patients with colorectal cancer harboring KRAS-G12C. As you know, KRAS colon cancer is a major unmet need. Only approximately 4% of tumors harbor G12C mutations, so it’s an unusual mutation, but what this study really demonstrated, is that in colon cancer, proof of principle combination of this inhibitor adagrasib plus cetuximab improved overall response rate, and the waterfall plot was seen in 28%, 28 patients, so relatively small numbers, but the response rate was 43%. And this is, some of these responses were quite durable. The investigators also presented a monotherapy data for adagrasib and the response rate was 22%. So this data is important because, number one, it sort of paves the way for future strategies for KRAS mutant colon cancer, and secondly, because it really proves that the preclinical work, which was done extensively to demonstrate the synergy, really panned out in the clinical study. Certainly this combination is being explored now in a Phase III randomized study against chemotherapy. But I thought it was an important data because so far in KRAS colon, we’ve been less enthusiastic about the strategy than, for example, in lung cancer. So it’s a drug, adagrasib, to watch out for. The other study, you know, I think in gastric cancer that really made a splash is in patients with heavily pretreated metastatic disease, looking at a important strategy with CAR T-cell therapy, looking at Claudin 18.2 CAR-T, and it’s an important strategy because certainly many of us are interested in claudin. There are monoclonal antibodies out there on the market. The target, this biomarker, which is an adhesion molecule, but it’s the first of its kind to show benefit some of these responses, so the overall response rate in the gastric cancer population was 48%. And, you know, I mean some of these responses were durable. I’m sorry, actually in gastric, it was 61% overall response rate. In all-comers, it was 48% because pancreas cancer was included as well. You know, we have to see cause it’s certainly an involved process with, you know, generating CAR-T, conditioning the patient, so we’ll have to see the survival data. The PFS didn’t look as good as I was hoping for. It was less than six months, but it’s an important step forward for CAR-T strategy in gastric cancer.
Lizzy Smyth: Yeah, I agree. So, I mean, I think that frequently we’ve seen good responses in hematological cancers for CAR-T. So far, they have failed in solid tumors, usually because of the lack of good targets, because we’re concerned about off-tumor on-target toxicity. Toxicity was minimal with this CRS. So cytokine release syndrome was observed, but mostly grade one and two, and the treatment was, in particular, well-tolerated. Zev, do you have any thoughts on the CAR-T data?
Zev Wainberg: Yeah, I mean I think claudin seems to be an interesting target, not just CAR-T, but you know, we’re awaiting obviously all sorts of antibody data and there’s an emerging number of ADCs, and it’s a unique target ’cause in some respects there’s not a lot of claudin activity outside of the normal stomach mucosa. So in some ways it lends itself to these sort of CAR-T ADC strategies, which I think are, you know, really exciting to see some efficacy in solid tumors. I can’t think of too many other examples in GI malignancies where we’ve actually seen responses with CAR-Ts that are like this. So I think there might be something to this. I share the points that Yelena made about, you know, durability, and the question is, you know, which we didn’t see a lot of detail on how the selection of the patients was determined, but compared to some of the other CAR-T stuff that’s been presented in GI malignancies, I thought this was pretty provocative. And, you know, it does kind of make me feel a lot more comfortable about claudin as a target as we await bigger datasets.
Lizzy Smyth: Agreed, it’s really a unique target, not an oncogene. I think that, which is, you know, makes it unique. I think that Yelena’s point is well-taken, that CAR-T is difficult to set up at the average institution. It’s very labor-intensive and we do see these responses in chemorefractory patients, we do. There are ways, I think, to work on the longevity of responses and this is early days for CAR-T and solid tumors, but the results are exciting, single center. They’re now expanding into Europe and into the States, I understand, so it’s certainly something we’ll be watching carefully over the next couple of years. We’re waiting also to see the paper, because all we’ve seen is a limited dataset of what was an interim analysis of the study, I believe.
Zev Wainberg: Yup.
Lizzy Smyth: So we’ll be watching this in future. Did you have thoughts, Zev, on the adagrasib data in colon cancer that you want to mention, KRYSTAL-1?
Zev Wainberg: No, I think Yelena made a good point. It’s really about the combination and, you know, I think we’ve known for, or felt for a while based on a number of preclinical studies that single-agent manipulations of KRAS, even something as directed as G12C inhibitors, is probably not going to be the way to go in GI malignancies. And it was both present from adagrasib and sotorasib I guess. So I think this kind of validates that strategy. I think as many have mentioned very akin to the BRAF mutant story in colon cancer, where simple blockade of the oncogene target by itself is insufficient and some combination strategy is needed. So I’m encouraged by it, too. I think we’ll wait to see in the next few years how we find these patients, there aren’t too many of them, but hopefully enough to accrue on these important studies.
Lizzy Smyth: So true, 4% of the population. We got to hit those redundant pathways, don’t we? Definitely with two drugs. Also exciting, very early days, happening in lung cancer first is the KRAS G12D inhibitors, which hopefully will make their way to colon cancer by the by.
SECTION 2: CheckMate 649 + DESTINY-Gastric02
Lizzy Smyth: So I think, Yelena, you’ve been very modest. You also presented a session yourself, CheckMate 649 update. Also the first results from the NIVO/IPI arm. Can you elaborate a little bit on what you presented?
Yelena Janjigian: Oh, you’re so kind, thank you. Well, you know, it was definitely an experience to come back to Paris and to present at the presidential session. We presented a two-year follow-up, a longer follow-up from CheckMate 649. As you know, that’s the Phase III study looking at chemotherapy with FOLFOX in combination with nivolumab, and compared it to chemotherapy. This was already presented and published in Lancet with a median of 12 months follow-up. So we presented a two-year follow-up from the primary endpoint and also a secondary endpoint and the third arm of CheckMate 649, which is the NIVO 1 [mg] + IPI 3 [mg]. So it was a higher doses of IPI. This was based on the design from the initial CheckMate 032 data, which I published in JCO, which showed that a higher dose of IPI was needed to have a more durable response and a higher response rate. Unfortunately, NIVO 1 [mg] + IPI 3 [mg] was not sufficient to improve outcome compared to chemotherapy, and the secondary endpoint of the study was not met. And as we see in other chemotherapy-only-containing arms, both from KEYNOTE-177, the MSI colon, and CheckMate 648, the NIVO, it’d be a squamous cell cancer. The survival curves cross at a later date in CheckMate 649, in favor of NIVO would be, but the difference was not meaningful enough to really show a benefit. The two-year data for FOLFOX NIVO continues to look… excellent. And the hazard ratio continued to directionally improve, demonstrating and sort of solidifying the role of immune checkpoint inhibition with combination with chemotherapy in first-line setting. So there were no surprises there. The adverse events and everything else looked very similar. There were slightly higher complete response rates with longer follow-up ’cause folks always ask, when do you expect to see the maximum response? And with two-year follow-up, we did see more complete responses on the NIVO plus chemo, so that was interesting. The other kind of, you know, notable fact about the new IPI arm is that overall response rate with MSI-high population was 70%. And as we know with NIVO/IPI, if you do respond even in MSS patients, their duration of response is nearly doubled with addition of, with dual checkpoint inhibitors in first-line setting. The overall response rate with NIVO/IPI was 26% in first-line, which is very interesting, right? ‘Cause it’s almost the exact same overall response rate in third and fourth-line. So there’s some interesting facts that we can sort of further dig into, but that was in a nutshell. CheckMate 649 confirmed that NIVO plus chemo is the right thing to do. Not NIVO/IPI.
Lizzy Smyth: Agreed. I think there’s more to explore for CTLA-4 inhibitors. There’s definitely value there. With limiting lower dose IPI, we know has lower toxicity and we’ll see the new biospecifics coming on. I think they’ll probably be integrated into care in future. So we have a good first-line standard of care, nivolumab and chemotherapy. Depending on where you are, PD-L1 status might be assessed. My question for you: MSI cancers, upfront chemo and immunotherapy, or immunotherapy alone? What are you two doing?
Yelena Janjigian: Zev, what do you think? What do you do?
Zev Wainberg: I should be asking you. I think in the majority of patients with MSI-high, I am very comfortable with checkpoint inhibitors alone. I feel like there is, both in the dataset that Yelena presented with the IPI/NIVO arm and with the, to be fair, pembro arm at the KEYNOTE-062, there’s really compelling data there in the MSI-high patients that probably the majority may not need chemo, upfront at least. And, you know, I think if I can offer a patient a good non-chemo combination in the right context, I think that it’s supported by most of those datasets. You certainly can’t go wrong by putting a patient with MSI-high on FOLFOX/NIVO, ’cause if you look at that curve, you know, we may never reach the median there, but you know, the question is do they need it? And, and I think, I don’t know if we’ll have better data than we have today. So to answer that question moving forward.
Yelena Janjigian: Yeah, I mean, I think that’s fair practically. What worries me is the KEYNOTE-177 survival curves were, even for MSI-high colorectal, the survival for the chemotherapy arm is improved. PFS is in favor, you know, for the first six to nine months. Also practically with the MSI patients, if the patient walks into your clinic with MMR-deficient gastric cancer and you’re a 100% certain that they’re MSI, I think it’s fair to discuss this, whether or not IO-chemo or IO alone is needed. It would worry me, that approach in patients with large disease burden or very symptomatic patients because the median time to response with immune checkpoint inhibitor without chemotherapy may be a little shorter. Although in many patients, the responses are brisk, too. Practically, often when the patient comes in and if you have tissue confirmation and if they’re symptomatic, and now that you have FOLFOX/NIVO in first-line setting, I often don’t wait for MSI testing to start treatment. And what I do is I deescalate the chemotherapy sooner, stop the oxaliplatin to minimize toxicity, perhaps continue them on 5-FU NIVO, or even if they’re really feeling great and there is brisk response, stop chemotherapy and continuing nivolumab. In other words, stop the chemo maybe after two months, as opposed to six months.
Lizzy Smyth: I think what you’re both doing is, you know, highlighting that we’re working with a limited dataset, that there is debate around what the best treatment is. So I agree that a chemotherapy-free option is very attractive. I was kind of influenced by the progression-free survival data, also that emerged from the KEYNOTE studies showing that there was a progression-free survival benefit for chemo-treated patients, but not overall survival. So I find that interesting. I think that what we are starting to learn, if you look at the data that came from the Korean trial, which was done in pembrolizumab showing that not all MSI tumors are the same and there’s variability in terms of the TMB, for example, and it may be in future that would perhaps we’ll choose patients with a higher TMB for anti-PD-1 mono, or maybe those with a lower TMB, we’ll need CTLA-4, and/or chemo. So I think there’s more to explore there, although whether those trials will be done with the currently available agents is another question. So I probably have to wait
Yelena Janjigian: And how quickly will-
Lizzy Smyth: Yeah, exactly, exactly. So I think it’s good to see debate, isn’t it? So another big trial, well, not so much a big trial, but big news in terms of the gastric cancer world at ESMO was the T-DXd data, so trastuzumab deruxtecan and the results from DESTINY-Gastric02. Would either of you like to comment on those?
Zev Wainberg: Okay, I’ll comment. I mean, you know, I think what we saw in ESMO was the first dataset of this drug in gastric cancer in a non-Asian population. So we, you know, we know that obviously the drugs has supportive data in Japanese and Korean patients and a randomized Phase II study showing endpoints all across the board were met efficacy with respect to all efficacy parameters when compared to investigator’s choice chemo, and that actually in rarest of circumstances led to an FDA approval in the United States off of a randomized Phase II dataset, for second-line and beyond. And this was the first time we got to see some data in non-Asian patients, which, you know, those of us, of course, treating have always felt that there’s different biology, different approaches, different epidemiology, and, you know, with a lot of GE junction tumors and, and so forth and so on. And so it was nice to see this dataset presented, I think the response rate here of single agent T-DXd in a decent number of patients, 79 patients, hitting 38, 40% is a respectable response rate. I think some would argue it was less thane the T-Dx one response rate seen in the, which it was, of course, in the Japanese and Asian datasets, the PFS of 5.8 months, or 5.7 months was indistinguishable from the median PFS reported in that New England paper. The challenge, and there’s a lot of differences between the studies as you guys know, but you know, one of the pros I think of the study was that it was very well-executed by demanding patients get rebiopsied and confirmed to be HER2-positive on enrollment, not just relying on archive tissue, and the argument could be made that as even better selection for patients we ought to have seen perhaps better efficacy than was reported in that original dataset. On the flip side, and I’m a bit partial to the flip side I must confess, I think that, you know, we didn’t necessarily go in expecting to see the same degree of efficacy with this agent as the Japanese and Koreans demonstrated. So I personally came out of it somewhat reinforced, albeit left with some questions about, you know, waiting for a maturity of the data, waiting for survival results, all of those things that, you know, we have come to want to see as we learn more about the drug’s activity in a different group of patients.
Lizzy Smyth: I agree. So I was pretty excited to see this, and I agree with you that, the response rate I was anticipating was maybe around 20%, half of what we saw in an Asian population. I was very pleased to see 40%, even though, agreed, it’s a selective population. Well, this is far in excess of what we see with paclitaxel and ramucirumab, so I have pretty good hopes for the DESTINY-04 study, which is the registration study in the second line, although you already have a registry for this drug in the United States, is this your standard of care second-line? Or are you using a third line? I’m interested to know.
Zev Wainberg: I think it depends on who you ask, but I mean, you know, it’s certainly, you know, it’s an option now for second-line and, you know, the label in the United States is left sufficiently vague that allows you to use it, and if you wanted to or after paclitaxel. So, you know, I totally agree with you. The proof will be obviously Gastric04 study to see if, you know, survival is improved in a large global study. That’ll be a critical study, which we can’t enroll to, as Yelena informed me, in the United States because it’s now FDA approved, but an important study for the world to be sure.
Lizzy Smyth: It is.
SECTION 3: MAHOGANY & chemo-free regimen in HER2+ gastric cancer
Lizzy Smyth: I’m going to side step a little bit into MAHOGANY, because I know that Yelena presented KEYNOTE-811 at ASCO, great study, very important, chemotherapy plus trastuzumab, plus or minus pembrolizumab first-line gastric cancer at HER2-positive, and what we saw at ESMO was a poster for a combination of margetuximab and anti-PD-1 antibody, and did either of you catch that poster or have any thoughts on a chemo-free option upfront?
Yelena Janjigian: Yeah, and it’s interesting because also at the mini orals, we saw the traz, nivolumab, ipilimumab data, if you remember, from the AIO study. So, you know, I think chemotherapy-free backbone is certainly enticing for many reasons. I think in HER2 in particular because if you have PD-L1 overexpression, and you know, HER2 overexpression, the rationale is certainly there to consider this, and MAHOGANY data is unique in a sense because it gives you a response rate with anti-PD-1, anti-HER2 without chemotherapy. The response rate looks great. This is a combination of pembrolizumab plus margetuximab, but the problem is the progression-free survival, the median PFS of 6.4 months. So the concern is there, if you induce a response, will the response be durable. And once again, as I mentioned for IO, IO combinations as well, the concern is the crossover on the curve. There was also INTEGA study presented from AIO during the mini oral session, similar idea, looking at NIVO plus trastuzumab with IPI and actually compared that to NIVO, traz, or chemotherapy, the responses were lower with anti-PD-1, anti-HER2 inhibition alone. I would love to move away from chemotherapy in first-line setting. I think it will be a challenge, not insurmountable, but probably not yet.
Lizzy Smyth: We’re in a good situation where we can even discuss this, bear in mind that’s also a double selective population, PD-L1-positive, HER2-positive. I think what I would like to see is, you know, questions asked in future by sequencing. So chemo-free followed by chemo. How does that equate with everything upfront? I don’t know, I mean, that sounds very much like an academic study to me rather than an industry study, but I think these are questions that we can ask in future. Zev, what are your thoughts?
Zev Wainberg: Very important questions, but very hard questions. You know, I think that one of the challenges certainly, I mean, obviously KEYNOTE-811 that Yelena presented with such an extraordinarily high response rate, when you think about how you’re going to power the next study and how you’re gonna improve on, at least in early efficacy readouts for response rate data, it is daunting to say the least to think about the powering of those studies. Obviously we’re waiting to see that PFS from 811 cause that could certainly help us. Everybody wants a chemo-free option upfront. I think there would be uniform- Nobody really wants to put these patients on chemotherapy if we can avoid it, but, you know, thinking about the future and how crowded this field has become all of a sudden, with not just margetuximab and other HER2 inhibitors, but also, you know, ZW25 and a whole host of other active agents that we know are active. It is getting very crowded in a hurry, and, you know, I’m thinking about the logistics of how the study design will actually work and it does feel very daunting at the moment.
Yelena Janjigian: It’s a good problem to have, and… I would probably think about this as co-occurring alterations and also what are the side effect profile of these agents? We’re also looking at antibody-drug conjugate trastuzumab deruxtecan in first-line setting, and, you know, just again, to be able to offer either chemotherapy-free or chemotherapy-light options, or non-platinum-containing regimens will come down to likely co-occurring alterations, level of HER2, right? Because we know that some of these ADCs actually may have an off-target effect, so if you have a heterogeneous tumor, or perhaps you have other co-occurring alterations, and you’re worried that HER2 is not the only driver, you may go after the bigger guns, but if you have a really homogenous tumor with very high level of HER2 amplifications that also suppress PI3-kinase, MET wild-type, then you could just sort of simplify your approach and use HER2-directed therapy alone.
Zev Wainberg: And, and-
Lizzy Smyth: Oh, sorry, Zev. Go ahead.
Zev Wainberg: Oh, sorry, sorry, Lizzy. No, I was going to say one other thing beyond what we’ve talked about so far is I’m excited to see how some of these stuff holds up in the earlier lines of therapy, right? I mean, I think we’re now at the point where, you know, we have all these metastatic datasets and not a lot of datasets in peri-operative approaches with HER2 inhibition, so we have some that have in fact failed, but you know, this is a new era and certainly I’m excited to see a lot of, you know, the next wave of studies looking at all of these drugs and various iterations, perhaps even chemo-free options peri-operatively so that’s something that, you know, I think moving forward, that would be nice, too.
Lizzy Smyth: I think that’s a really interesting question. Hopefully we’re going to cure more patients. Are we going to see the KEYNOTE-585 data at ASCO GI? Possibly. So the question is will we be able to add IO to just platinum 5-FU chemotherapy or will we add it to FLOT? And I think that’s an open question until we see the results of that study. I agree with you, Yelena, that T-DXd is very attractive for platinum-refractory patients. What about those patients who progressed soon after FLOT? We’re not really excited to give them cisplatin or oxaliplatin. I think T-DXd is very likely to have a role for those patients. So that’s a really great discussion about the kind of plethora of development in the HER2 space at the moment. Was there anything else that stood out to you? We saw a host of IO studies coming from our colleagues in Asia, looking at various PD-1 inhibitors with chemotherapy first-line. Did you reflect on any of those or is it all, we’re just seeing a class effect?
Zev Wainberg: Class effect, I mean, I think, you know, especially in squamous cell, the data’s pretty reproducible. I think you look at the hazard ratios across the board from what’s been presented in, you know, with NIVO and pembro and now with, you know, sintilimab and toripalimab, and I think the hazard ratio, it’s remarkably similar, maybe a little more so in squamous than in adeno, but certainly in adeno to some extent as well. I mean, you know, some of these drugs, we’ll probably never see in our parts of the world, but it is reassuring-
Lizzy Smyth: Yes.
Zev Wainberg: …because I think the more you see confirmation, the more you’re reassured that, you know, the class effect is real.
Lizzy Smyth: Yeah, and even for gastric cancer, Yelena, I think that the PD-L1 level of positivity and hazard ratios were very similar to CheckMate 649, because there’s always been a lot of discussion about the high proportion of patients who are PD-L1-positive and I think all of us were pretty reassured to see the same data in the studies presented at ESMO.
Yelena Janjigian: That’s right, yeah. I think what I’ve learned from the squamous data is, as you know, the taxane-based backbones used in Asia are different from what we have developed for these global studies. And I wonder if for squamous, if we should consider taxane-based backbones because the responses even on the standard of care compared to arms, and hazard ratios in general looked, to me, better, certainly the data out of China and the biology of tumors there are different, but it was tempting for me to consider, to use taxane-based therapy in first-line in my squamous patients.
Lizzy Smyth: Great, agreed. I do think that, on reflection, though, the three-weekly taxane plus a platinum is possibly slightly difficult to tolerate. We know FOLFOX is so easy to tolerate, or CAPOX, and I think it would probably stay the standard of care just for that reason-
Yelena Janjigian: If you want it to be.
Lizzy Smyth: But I agree with you r.e. the response rates.
Yelena Janjigian: Yeah, I mean, but if you wanted to be a purist, it’s not CAPOX or FOLFOX and 590, you know. It’s also every three weeks high-dose cis, so I absolutely do not advocate using high-dose cisplatin in this disease, but a taxane-based approach with sort of mitigation of some of these, I would say, antique regiments is something to be considered.
Lizzy Smyth: If I want to give cisplatin, I’ll have my oncology day unit after me for the nine hours that they need to start giving.
SECTION 4: PRODIGE 24 in PDAC
Lizzy Smyth: So I would like, before we wrap things up, are there any other news from ESMO that you feel worth discussing or have we touched on everything that’s important in upper GI cancer? Oh yes, I think there was a pancreas cancer study that we wanted to discuss in fact. Was it an update of PRODIGE 24?
Zev Wainberg: Yes, indeed, Lizzy. And so, you know, I think pancreas cancer, you know, doesn’t have as much great stuff going on as we do in upper GI cancers. There’s not a large oncology mean that goes by now where we’re not seeing practice-changing data in gastric cancer. We’re getting a little spoiled. And our friends in pancreas cancer, unfortunately, are not quite as fortunate, neither with respect to new drug development, nor with respect to any immunotherapy combinations. But we did see at ESMO 2021 long-term data from the PRODIGE 24, and I think, you know, reassuringly, what you want to see in a long-term dataset like this is that the five-year survival holds up. And it certainly does. I mean, PRODIGE 24 randomized patients with resectable pancreas cancer after surgery to either FOLFIRINOX, modified FOLFIRINOX I should say, and gemcitabine, and, you know, five-year disease-free survival rate was 26% versus 19%. Overall survival rate is 53 months, which is heretofore not been seen in pancreatic cancer, versus 35 months. So both Kaplan-Meier curves hold up, both hazard ratios hold up. Really, I think, you know, not a huge surprise, but always reassuring to see that, you know, what has become the standard of care for these last few years is reinforced in long-term survivorship. So clearly, if any patient is a candidate for FOLFIRINOX in the adjuvant setting of pancreatic cancer, this is the way to go. Pancreatic cancer is trying to follow in the way of gastric cancer, right? As thinking about doing everything upfront, and you see in more and more studies and more and more centers giving neoadjuvant approaches to pancreatic cancer, even in, I would say, resectable patients, purely resectable patients. There’s not a large randomized dataset yet. There are some datasets from Japan just published in JCO. If you saw the JCOG study showed a survival advantage to resectable pancreas cancer, giving upfront chemotherapy over chemotherapy in the adjuvant setting, but that’s the way we need to go, I suspect, in this disease as well. So I think pancreas cancer-
Yelena Janjigian: What I also found interesting from PRODIGE 24 update is that, and you sometimes run into this in adjuvant setting where the patient is just tolerating the therapy okay, but just wants to stop or is exhausted, and what PRODIGE 24 study update suggested is if you are able to get all the chemotherapy in, those patients tend to do better. Of course, that’s because probably they’re more fit and have a more favorable biology, but nonetheless, to me, it was a learning point, and probably true for a lot of different adjuvant therapies, is that if you can finish, please finish and don’t stop early just because of patient preference.
Lizzy Smyth: Great, and hopefully in the next couple of years, we’ll see the same advancements for patients with pancreas cancer and bowel cancer with respect to all these immunotherapies, and we’ll crack those immune deserts for those patients in future.
Yelena Janjigian: We’re due for a breakthrough in pancreas cancer.
Lizzy Smyth: I think so, too. Yeah, I think so, too. Well, I would like to thank both of you for a great discussion this evening. It’s great to hear your insights on the data that was presented at ESMO 21. I do hope that we get to see each other sometime over the next year in real life. And thank you all for joining us on VJOncology this evening.