EVC: Welcome, I’m Professor Eric Van Cutsem. I’m from Leuven, Belgium and I work there as a GI oncologist. Welcome here at ESMO 2019 in Barcelona for this ecancer educational session. I’m happy to be joined by Dr Teresa Macarulla from Vall d’Hebron University in Barcelona. Teresa, welcome.
TM: Thank you.
EVC: We will discuss on pancreatic cancer, a difficult to treat disease. These days we are making some progress. One of the important aspects where we made some progress this year was understanding the patients with germline BRCA mutation who are treated with olaparib. Teresa, can you update us a little bit on this data and also on the new quality of life data that were presented here at ESMO 2019?
TM: Yes. This year we presented the results of the quality of life in the patients included in the POLO trial. I think that’s an important point and it’s important results because in the maintenance treatment in pancreatic cancer we have to consider if the patient maintains a good quality of life. In fact, we want that patients that stop with chemotherapy and side effects of chemotherapy we would like that those patients maintain that quality of life. In fact, this analysis demonstrated that patients treated with olaparib maintained their quality of life with the same level as patients treated with placebo. So that’s good because it means that we are controlling the tumour and we are not giving to the patient side effects that affect the quality of life of those patients with pancreatic cancer. I think it’s an important point.
EVC: What are the implications in your daily practice from the POLO study in view of the strategy, platinums and BRCA mutations, in view of the fact that we have the olaparib data and in view of the fact that in many countries many physicians often start with first line treatment of gemcitabine nab-paclitaxel which is not the optimal setting in the BRCA mutant patients. How do you tackle that in Barcelona?
TM: Yes, we are dealing how to test BRCA in our situation, in our countries, in Europe. So now it’s easy when you have a patient, a young patient, a patient with some other tumours or an important family history of cancer. These cases are easier because we normally start with FOLFIRNOX or with gemcitabine and cisplatin, it depends on the ECOG of the patient, and we perform the test of the BRCA test. But, of course, the more difficult situation is what we can do in a patient 60 years old with no family history of cancer, with no history of cancer, how we can test. The ideal situation is to test all of our patients because we know that some patients present these mutations without any other situation but we have to deal with this in Europe. At this moment it is not so easy.
EVC: The trial, the primary endpoint of the trial was progression free survival on olaparib. Some people challenge us sometimes that there is not yet any survival benefit. Is that in your practice anything that has implications for you?
TM: Of course. This trial was not powered to demonstrate a benefit in overall survival and that’s an important issue. And also the data is immature so we have to wait more and see what happened with the cohorts. But also when you treat pancreatic cancer and you have a patient with a BRCA that responds to platinum and has this response, like in the POLO trial it was reported it’s more than 20-25% of the patients respond to olaparib, and then maintain this response for two years, for example, this is something that, for sure, in your patient impacts on the overall survival. So for the trial we have to wait but when you see in your clinics this kind of patient, for sure this patient benefits from the treatment and also the overall survival of those patients.
EVC: I completely agree, I share this experience also that there are some patients, it’s of course not everybody, but who have a long-term benefit. Probably here the medians will not reflect everything and the trial was indeed not powered. The follow-up is short until the first analysis that we published so we have to wait longer. But I do believe that also therefore the quality of life data that’s represented here, that they are very important because there is no negative impact on the quality of life with olaparib in this setting.
If you change a little bit also in pancreatic cancer towards the adjuvant and neoadjuvant treatment, we have seen this year the data of gemcitabine nab-paclitaxel, the APACT trial being presented. At ESMO there were some further presentations on this study. Then also an interesting field where there is more and more interest, if you compare that with four or five years ago, is the neoadjuvant treatment. To come out and to look at what is now the best strategy in patients with either borderline resectable or patients with unresectable disease in this setting. Our German colleagues have presented the NEOLAP study in this regard in the neoadjuvant setting with two different treatment regimens in the neoadjuvant treatment. Can you update us on the results and on the impact, Teresa?
TM: Yes. They presented the results of this phase II trial, randomised phase II trial, with patients initially locally advanced. I’m not so sure that some borderlines are included in the trial. They treated the patients with gemcitabine and nab-paclitaxel in order to produce some effect in the stroma and then after two cycles patients were randomised to be treated with FOLFIRINOX for two months or continuing with gemcitabine and nab-paclitaxel two more months. Then the patients were considered for resection of those patients. In fact, the surprising thing for me is that they presented a high response to this treatment and a high resectability because around 40% of the patients treated with FOLFIRINOX can be resected with a high number of patients with an R0 resection that’s important. So I think in the locally advanced, even in the locally advanced of course, in the borderline every day we know that we have to treat more of those patients with neoadjuvant treatment. But even in locally advanced those patients every day with better neoadjuvant treatment can be resected. Our surgeons are better, they are learning how to manage with these vascular resections, and every day this is increasing and this trial demonstrated it. It impacts in the prognostic of our patients with locally advanced.
EVC: How would you treat today a patient in locally advanced pancreatic cancer? FOLFIRNOX? Gemcitabine nab-paclitaxel? Or would you say let’s start with FOLFIRINOX, if the tumour is not resectable integrate chemoradiotherapy at that moment? What’s your common practice in Vall d’Hebron?
TM: First of all we treat those patients and we present always these patients in a multidisciplinary team. It’s so, so, so important to be implicated in these patients. We tend to use more, maybe, FOLFIRINOX for the question that maybe you have higher response rates. We have really good experience with FOLFIRINOX but we have no data so it’s an impression. We try to perform an exploratory laparoscopy in all those patients if we do not have a progression disease in the CT scan because sometimes the surgeon has seen that there is no tumour around the vessels and they can resect that patient. So we try to use this strategy.
EVC: That’s an important message and that’s also our experience, that if patients who are pre-treated with FOLFIRINOX that judging the resectability after four cycles, or six or eight cycles of FOLFIRINOX is not always easy. Sometimes the tumour has shrunk more than what you see on the scan and becomes resectable in this setting. But one of the challenging topics is also if the tumour is not yet resectable whether we should integrate at that moment between FOLFIRINOX and eventual surgery radiotherapy in this setting. Some radiation oncologists are in favour of that. We don’t do that as a standard in Leuven but occasionally we do it in some patients – if we don’t see a regression on FOLFIRNOX we may consider doing that. Do you do that often?
TM: Not so often but normally I use radiotherapy when the patient is not resectable, when the surgeon says to me, ‘That’s for sure not resectable.’ As a local control I use sometimes radiotherapy. I know that the LAP-07 is negative in overall survival but is positive in local control and also in the time that the patient… it’s longer the time that the patient can be without treatment if you give radiotherapy. So I give radiotherapy but normally after the surgeons say to me, ‘This is not resectable.’
EVC: Yes, so it’s clear that multidisciplinary discussions are crucial in this disease, especially in local disease, and multimodal treatment options may make more patients resectable. We still have to remind that resection can lead to cure in some patients although many patients still have a relapse. But it’s important for these individual patients. So this multidisciplinary collaboration is important and too what we spoke on in the beginning is that olaparib is the first targeted agent in an enriched population, the germline BRCA mutants, which is 6-7% of the patients, where there may be some benefit in this setting. So we are optimistic that by further unravelling and working on the molecular biology, on understanding the stroma interactions, on understanding maybe some metabolic pathways that in the future we will make further progress in pancreatic cancer. So we are always optimistic in this setting.
EVC: Thank you very much, Teresa, and thanks also to all of you listening to us for this ecancer educational activity from Barcelona ESMO 2019. Thank you.