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Jan 24, 2019

 Key Takeaways from the 2019 Gastrointestinal Cancers Symposium with Dr. Stephen Leong


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Welcome to the ASCO Daily News podcast. I'm Lauren Davis, and joining me today is Dr. Stephen Long, associate editor of ASCO Daily News.
Dr. Long is associate professor in the division of medical oncology and is a translational researcher in the GI and developmental therapeutics programs at the University of Colorado Cancer Center.
Dr. Long, welcome to the podcast.
Thanks for having me. It's a pleasure to be here.
Dr. Long, you've just returned from the Gastrointestinal Cancers Symposium. How was this year's event compared with previous years?
First of all, I love you GI ASCO. I always find it informative. And I love the format of the talks and presentation.
This year there was no significant practice changing presentations like in years past. However, there were still some excellent presentations and talks.
And what were some of the presentations that stood out to you?
There were some reports of a couple of clinical trials that sort of intrigued me. One was KEYNOTE-181. This was a phase III study comparing pembrolizumab monotherapy versus standard chemotherapy in patients with local events and metastatic esophageal cancer in the second line setting.
They reported a significant improvement in overall survival in patients with PD-L1 combined positive score of greater than 10. And these patients received 9.3 months overall survival compared to 6.7 months for those who received [INAUDIBLE] choice of chemotherapy, which then consists of paclitaxel, docetaxel, or irinotecan.
In addition, pembrolizumab was better tolerated and had a better safety profile.
What made it really intriguing was of the total 628 patients that were enrolled in the trial, 64% of them had squamous cell carcinoma of the esophagus, which is unusual, especially in a phase II setting.
And even though the study had a statistic overall survival benefit, in the squamous cell carcinoma cohort, there was a non-statistical trend in overall survival of 8.2 months versus 7.1 respectively.
Pembrolizumab did boost the objective response rate compared with chemotherapy in the PD-L1 CPS greater than 10 and a response rate of 21.5% versus 6.1%. And then squamous cell carcinoma, it was 16.7% versus 7.4%.
That leads to a whole bunch of questions. One, should we improve our PD-L1 scoring by including a CPX score greater than 10 and making our predictions based off that? In addition, should pembrolizumab expand its indications to include squamous cell carcinoma, since presently in the United States, pembrolizumab is only approved for adenocarcinoma.
Also, there were the reports of the phase II ROAR study, which was looking at biliary tract cancers with BRAF V600E activating mutations. And these patients received a combination of dabrafenib, a BRAF inhibitor, and trametinib, a MEK inhibitor.
There were 33 patients. And they had an objective response rate of 42%. All of them with partial responses. And 7 of the 14 patients with responses had the responses lasting more than six months. And adding those with stable disease, they had reported a disease control rate of 88%.
They looked at survival data. And the median progression free survival in this cohort was 9.2 months with an overall survival of 11.7 months.
And to put this into context, usually second line biliary tract cancers we rarely ever see survival being more than five months. And these PFS and overall survival is very comparable to the first line setting for gemcitabine cisplatin, where the original study showed a PFS of eight months and overall survival of 11.7 months.
So this potentially could be another treatment option for people with V600E biliary tract cancers.
And then there were the preliminary results of a single phase II study at Memorial Sloan Kettering, which was evaluating pembrolizumab in conjunction with trastuzumab HER2 antibody with CAPOX and those with HER2 positive metastatic esophageal gastric adenocarcinoma.
They had 32 patients with the overall response rate of 87%. They reported three CRs and 25 partial responses. And then when you factor in the stable disease, they had 100% disease control rate. And all the patients had some degree of tumor regression. The PFS were 11.4 months with an overall survival having not been met after six months.
This is extremely exciting, and this has already led to the development of a global phase III study, which will be known as KEYNOTE-811.
That's great. That sounds very promising.
Were there any research presentations that you were interested in?
Oh, yeah. There was a lot of great preclinical work. One of the most intriguing was in pancreatic cancer, where the Canadians did a study known as COMPASS, where they took advanced pancreatic ductal adenocarcinoma, and these patients underwent whole genome sequencing, as well as RNA sequencing of their tumors, prior to the initiation of first line chemotherapy with either modified FOLFIRINOX or gemcitabine and abraxane.
Treatment outcomes were then compared to their molecular characteristics. The data suggests that chemotherapy differs depending on the transcription features of the tumor.
So for example, the best survival data came out of those patients with the classical ductal adenocarcinoma subtype that were treated with FOLFIRINOX. And they had a median survival of 7.17 months.
And when they were compared to the basal-like subtypes and were treated with FOLFIRINOX, they had a median progression free survival of 2.5 months.
Now, patients with the basal-like subtype actually had a better response to gemcitabine and abraxane, which had a PFS of 5.65 months compared to the classical subtype, where they had median progression free survival of 4.93 months.
So in summary, those with the basal-like subtype actually had a resistance for FOLFIRINOX. In addition, the researchers also mentioned that GATA6 RNA expression significantly correlates to the PDAC classic and basal-like molecular subtype. So it could actually be used as a marker in determining subtypes. And all this put together means that we could potentially identify patients who have a better chance of responding to FOLFIRINOX versus gem abraxane in the first line setting in pancreatic cancer.
And obviously there needs to be more work to validate this, but this actually is quite intriguing.
Also, there was data from the amino scoring testing, which was looking at its test in high risk stage 2 colorectal cancer patients. And for those who are not familiar, patients with stage colon cancer have a poor prognostic if they had a T4 disease, had fewer than 12 lymph nodes removed, had a point differentiation subtype, and also had evidence of vascular emboli, lymphovascular invasion, perineural invasion, or actually had a presentation of bowel obstruction or bowel perforation.
And these patients are often offered adjuvant chemotherapy following curative resection due to their high risk of recurrence.
The amino score test measures the density of CT3 positive T cells, as well as cytotoxic CDH cells within and surrounding the tumor to gauge the strength of the host immune response at a tumor site. So therefore a high amino score indicates a high anti-tumor immunity, which correlates with a low risk for disease recurrence.
And these investigators looked at 1,130 patients with stage two colon cancers. And their conclusion for time to recurrence was those with high risk disease with high amino scoring compared to those with low risk disease had a very similar five-year survival of 87.4% versus 89.1% respectively.
In contrast, if you have a high risk disease and a low amino scoring, your five-year time to recurrence was only 72.2% in the absence of adjuvant therapy. So this could potentially be used as a prognostic tool for those who are high risk stage two in the future.
What about education sessions? Were there any that caught your attention?
So my favorite was the neuroendocrine session. Neuroendocrine, as most people know, is a pretty rare disease population. However, there has been significant advances in the past few years with new drugs, new understanding of the biology, new diagnostic procedures, as well as testing.
And it was a great panel of leading experts to help us navigate the new landscape of neuroendocrine and understanding how we should be approaching this. So that was my favorite session.
Were there any other takeaways that were important during the symposium?
There were a few other presentations I thought that were quite interesting. The Japanese presented their Prep-02 or JSAP-05 trial.
And this was the first study to ever demonstrate the efficacy of neoadjuvant therapy in resectable pancreatic cancer. And their neoadjuvant chemotherapy regimen was a combination of gemcitabine with an oral drug S1. And they showed that it met its primary endpoint of overall survival of 36.72 months in those patients who received neoadjuvant therapy versus 26.65 months in those who went from upfront surgery.
And for the Japanese, which tend to do upfront surgery followed by adjuvant chemotherapy in the past, I think this may be a shift in their paradigm, where this could be the new standard in Japan of using neoadjuvant therapy prior to surgery.
Also, there was the oral drug trifluridine and tipiracil, which was studied in a phase III metastatic gastric and GE junction adenocarcinoma for those who have received two previous line of therapies. And they were randomized to the drug versus placebo. And it demonstrated a 2.1 survival benefit over placebo.
And their main concern was a lot of these patients end up getting gastrectomies. But being an oral drug, could that affect its efficacy? And it seems like this benefit was also seen in those who had a gastrectomy versus those who didn't as well. So this potentially could be another option for those in the third line setting for gastric cancer.
However, the big debate is even though it met its overall survival, is 2.1 months clinically significant? And I guess we'll have to have more data regarding safety and tolerability before we can make that decision.
There is also the French GRECCAR-6 trial, which was evaluating the optimal time to surgery following chemoradiation for rectal cancer, where patients who underwent neoadjuvant chemoradiation were randomized to waiting 7 or 11 weeks prior to a mesoresection of the rectal cancer.
They demonstrated that they had very similar path CR rates between the two. But more interesting, they found that if you had a good disease response to chemoradiation, there was no difference in disease free survival if you waited 7 weeks versus 11 weeks prior to surgery.
However, if you were a bad disease responder, you had a poorer disease free survival if you waited more than seven weeks. However, this was not statistically significant.
And then the authors concluded that we shouldn't be waiting more than seven weeks prior to surgery following neoadjuvant chemoradiation for rectal surgery.
Thank you so much.
Again, today my guest has been Dr. Stephen Long. Thank you for being on our podcast today.
And to our listeners, thank you for tuning into the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple podcast.