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Markus Wartenburg New Horizons 2020

Markus Wartenburg

The New Horizons GIST 2020 Virtual Meeting kicked off on Thursday September 10th at 8am EST. Meeting since 2003, these patient advocates for various cancers split off to a GIST-only meeting several years ago. This year’s meeting, originally planned for Berlin, Germany, was held virtually September 10-12th. At the New Horizons (NH) GIST conferences, participants traditionally focus on discussing critical information about GIST that impacts the global GIST patient and medical communities. Participants have opportunities to interact with leading GIST experts, learn new medical and scientific information about GIST, exchange best practices and discuss advocacy issues.


This year’s New Horizons GIST Meeting was dedicated to dear friend, GIST patient & advocate, Dr. Nikhil Guhagarkar, who passed away in May 2020.

Markus Wartenberg, of the German Sarcoma Foundation/SPAEN and NH Steering Committee Member, launched the meeting with a gracious welcome and opening notes. Markus noted that this was the 17th year for the New Horizons conference and that this year’s meeting was dedicated to the memory of GIST patient, friend and advocate, Dr. Nikhil Guhagarkar, of Friends of Max, India, who passed away this May.

Novartis logoIndustry representatives from Novartis, Blueprint Medicines, and Deciphera (conference sponsors) shared their thoughts with the online participants as well. Geoff Cook of Novartis shared, “One of the things I’ve been really impressed by as someone who’s worked in advocacy for a long time now is that the first organizations in our systems to reach out to patients when this crisis began and give them information around what were the implications of COVID for patients for various diseases were the patient groups. They were faster than the healthcare systems, faster than the CDC. Support of these meetings is really one of the cornerstones of the strategy we have to try to help organizations to meet the needs of patients in ways that pharmaceutical companies and healthcare institutions can’t. You can provide guidance and feedback from a peer to peer perspective, where you have individuals with GIST who really understand the issues for newly diagnosed people. You can share insight and experience in a profound way that we know is unique.”

Blueprint MedicinesBlueprint’s Nick Taylor agreed with Cook’s comments and added that their core value is to make a difference in patient’s lives by looking for ways to incorporate the patients’ perspectives, understand the patient journey and how to support the broader advocacy community. Taylor also thanked the patient organizations and advocates for the collaborative efforts of which they have taken part.

Deciphera LogoStephanie Bryant said on behalf of Deciphera, “We value every aspect of the GIST journey and it’s through interactions like these with the patient communities that the company gets a real glimpse of the realities of living with GIST which helps us better understand the needs of patients and to hear the patient voice.”

Day 1

The first session was moderated by a representative from the Swiss GIST group, Martin Wettstein, a GIST patient and advocate and also a Steering Committee Member. Dr. Hans Gelderblom, a medical oncologist from Leiden University Medical Center, in Leiden, Netherlands, reviewed statistics on the frequency of GIST, its unique characteristics and clinical presentation as well as the structure and biology of c-KIT. He continued his GIST Overview with a general review of treatments and molecular pathology and spoke briefly on his view of the importance of plasma level testing, finishing with statistics on progression free survival. Dr. Gelderblom then answered questions collected by Martin from the participants.

In session two, Dr. David Josephy, President of GIST Sarcoma Life Raft Group Canada, presented an overview of the biology, genetics and pathology of GIST. Dr. Josephy is known for his ability to relay complex scientific principles in a way that is easily understandable for the lay person. For example, in explaining why metastases that have migrated to another site are still GIST, and not another cancer such as liver cancer, he shared an illustration representing an Englishman visiting New York City. “An Englishman is still an Englishman, even if he is in New York.” He emphasized takeaways from the earlier presentation, especially the importance of seeing a GIST specialist and the vital nature of mutational analysis. The overview of how cancer develops, and more specifically, how the types of GIST develop was well explained. At the end of the session, he answered questions ranging from basic to more complex, engaging in dialogue with the audience.

With the last session of day one, Markus Wartenburg introduced a pre-recorded presentation by Dr. Peter Reichardt, Assistant Professor and Head of the Department of Oncology and Palliative Care at the Helios Klinikum Berlin-Buch in Berlin, Germany, and Director of the Cancer Center Berlin-Buch and the Sarcoma Center Berlin-Brandenburg. Dr. Reichardt discussed surgery of a primary tumor as a treatment for GIST.

After a brief history of the disease, Dr. Reichardt dove right into the various clinical decisions for the treatment of a GIST patient. An all-encompassing theme for the conference was the importance of mutational testing, with Reichardt deeming it “mandatory.” He delineated circumstances where surgery should always be considered, and cited numerous studies that provided data for decision making in terms of neoadjuvant, adjuvant and the duration of treatment. Since the session was recorded, Markus discussed several pre-prepared questions for review.

Day 2

Day two of the event began with Steering Committee Member and LRG’s VP of Program Services, Sara Rothschild, facilitating. Dr. Albiruni Ryan Abdul Razak, Sarcoma Lead for Medical Oncology at Princess Margaret Cancer Center & Mount Sinai Hospital in Toronto, Canada, spoke on metastatic (advanced) disease, which was the fourth session presented during the conference. Dr. Razak reviewed the character of GIST and its frequency, noting that with metastatic or advanced disease, metastasis more often occurs in the liver or peritoneum. The doctor continued with details on clinical studies, side effects related to dosage, and types of progression.

Comments worth noting included that the first treatment considered is surgery; for those with unresectable tumors, medication offers, for most, a degree of response, though 1 in 10 may not respond to any dose of Gleevec. Off-label as well as approved medications were covered and one comment worth mentioning was that “toxicity is what the patient says” when discussing whether or not a medicine that might be working is actually tolerable for the patient. He also repeated that “Mutational testing is imperative.” Dr. Razak also discussed a unique use of specialized PET scans for clinical decision making. He answered questions from participants following his presentation. Questions, posed by moderator David Josephy, LRG Canada, Steering Committee Member, ranged from approval for scans, the reasons for long-term response to imatinib and secondary mutations, and appropriate dosages for certain mutations.

Session 5 was entitled, “ Progression of Metastatic Disease Under Drug Treatment.” This session was moderated by LRG Senior VP, Laura Occhuizzi. Dr. Breelyn Wilky, Director of Sarcoma Translational Research at the University of Colorado, discussed treatment options for patients with progression Dr. Wilky began by discussing the overall biology of progression, and moved on to looking at KIT-resistant mutations, as well as tools to identify these biomarkers. She presented two case studies, each showing the need for personalized treatment decision making. Discussing the two types of progression, localized and widespread, she was able to illustrate that all progression is not equal. This further highlighted the need for patients to see a GIST expert whenever possible.

Finally, Dr. Wilky shared several alternative treatments for progression, explaining ablation and embolization among them. Outlining the protocol for making decisions on treatment for fifth line and beyond, she discussed the use of ctDNA (circulating tumor DNA) and genomic sequencing, sometimes involving repeating a tumor biopsy. Laura then moderated questions from the audience. Dr. Wilky also spoke about the importance of side effect management, the importance of discussing side effects with your physician and making a decision together with the patient when it is time move to a different treatment line.

In Session 6, “Introducing New Treatment Options in GIST”, moderated by Sara Rothschild, Dr. Jonathan Trent, of Sylvester Comprehensive Cancer Center, University of Miami, discussed the latest treatment options for GIST patients. Dr. Trent emphasized the importance of mutational analysis, outlining the GIST subtypes driving treatment. Repeating what throughout the conference proved to be a prevalent theme, he stated that, “Patients waste valuable time and money often taking medication that has no effect on their tumors. Every single GIST patient needs to have mutational testing. It is not acceptable to think otherwise.”

Dr. Trent showed data that indicates that only 30% of GIST patients are getting testing for KIT. He is currently studying the value of circulating DNA testing, especially for those who progress on TKIs. He went on to discuss in detail some of the more promising clinical trials, and emphasized the importance of personalized side effects management, using side effects profiles to help make decisions in prescribing medications.

Blueprint Medicines Navigator study showed incredible activity, and favorable activity in Exon 18. FDA approved avapritinib in the US for PDGFRA exon 18 mutation, including D842V mutations, for patients with unresectable or metastatic GIST. There was definite activity in unselected patients with avapritinib in 4L and beyond. Deciphera Pharmaceuticals Invictus study showed ripretinib as statistically significant with PFS and OS. The data shows lots of stable disease in patients (some times out to 12 weeks). FDA approved ripretinib in the US for 4th line therapy for GIST.

Dr. Trent answered questions, and spent some time encouraging advocacy efforts to get regulatory agencies, oncologists, and insurers all on the same page to assure access to mutational testing.

Day 3

Kicking off the third day of New Horizons 2020, Jayne Bressington of GIST Support UK introduced Dr. Ramesh Bulusu, Addenbrooke’s Hospital, Cambridge University Hospitals, UK, and Dr. Ruth Casey of Cambridge University Hospitals, UK, who presented on the challenges of treating patients with rare subsets of GIST

Jayne offered some personal history of how she became involved in PAWS GIST UK. This patient advocacy organization maintains a patient registry and tissue bank, and is actively involved in working with researchers on cell line research.

Dr. Bulusu began with an overview of GIST, moving on to the specifics of the 15% of patients who are not KIT or PDGFRa. He spoke about the term “wildtype,” believing strongly that we should abandon that term, using instead specific mutational subtypes. He stated that SDH mutations are both “fascinating” and “challenging.” The NF1 subtype is the most challenging to treat. New oncogenic drivers are being discovered all the time, with BRAF mutant GISTs, NTRK fusion GISTs , NF1 and FGFR pathways as well as succinate dehydrogenase (SDH) deficient GISTs being targeted. Descriptive terms for these include quadruple negative GISTs (KIT, PDGFRA, BRAF, wildtype and SDH preserved), and Quintuple negative GISTs (KIT, PDGFRA, BRAF, wildtype, SDH preserved, no NTRK fusion).

He outlined the standard of care for non-KIT PDGFRa GISTS, indicating that the oncogenic driver needs to be identified, e.g. BRAF would be treated with BRAF kinase inhibitors, NTRK fusion GIST with NTRK inhibitors. In terms of the standard TKIs: imatinib has no benefit, although there have been anecdotal reports of response that could be due to the natural history of GIST. Sunitinib has shown some activity in SDH-deficient GIST. Regorafenib has shown some response in SDH-deficient and in NF1 GISTs. There is concern about the long-term effects on younger patients.

One exciting technique mentioned was the use of MRI spectroscopy in detecting succinate in tumors in vivo. Also, the use of SIRT therapy, injecting a agent directly into the tumor. This has been used in colon cancer. Dr. Bulusu shared helpful charts concerning asymptomatic SDHx carriers.

Dr. Casey’s background in endocrinology and interest specifically in inherited (germline) GISTs aided her in providing an overview of SDH-deficient GIST. With SDHC epimutation, specifically Carney Triad, hypermethylation plays a role.

Screening protocol for patients with an SDHC epimutation was outlined stating it was not clear. Their recommendation was that screening for PPGL should follow similar guidelines as for SDHA germline mutations. No family screening is recommended.

Two takeaways from their presentation that are key: treat the patient to tolerance, not toxicity, and see a GIST specialist. Dr. Bulusu ended with a fervent cry for more collaboration.

The second session of the day was “Following the Research”, moderated by Pete Knox, LRG’s Senior Director of Research. Dr.Robin Jones, Institute for Cancer Research, London (UK) discussed potential treatments in the research pipeline. He provided a concise overview of the treatments available, both approved and off-label, indicating that in many cases the country you are from will determine availability of off-label medications.

As in previous sessions, Dr. Jones discussed the importance of side effects management. He then discussed current promising clinical trials as well as combination therapies and immunotherapy. The patient/doctor relationship is at the heart of treatment success, requiring a careful discussion at every stage. He cited three main stages: Discussion of conventional options, discussion of clinical trials, and finally thinking “outside the box.” Like some of his colleagues who spoke prior to his own presentation, Dr.Jones ended with a call for collaboration among oncologists, researchers, patient advocacy groups and regulatory agencies to unite for the welfare of patients. Dr. Jones answered a number of questions from the audience concerning worries about off-label treatments, drug access, and talking to your physician about an off-label treatment.

The final presentation of the day, which was the 9th session of the conference, was moderated by Piga Fernández, Fundación GIST Chile and The Life Raft Group, and Ginger Sawyer, GIST Support International. Dr. Gina D’Amato of Sylvester Comprehensive Cancer Center, University of Miami, US discussed the challenges inherent in assuring that patients receive accurate diagnosis, and access to quality treatment, as well as the importance of side effects management.

Dr. D’Amato’s presentation was extremely approachable, She emphasized the importance of adherence to treatment, and the challenges faced by side effects, and also offered strategies for the management of those side effects. Supporting the words of other presenters, she drove home the importance of mutational analysis, and of seeing a GIST specialist. With the advent of telemedicine in this pandemic, it has opened up the opportunity for local oncologists to partner with GIST experts for quality assurance. Dr. D’Amato also discussed at length the importance of diet and exercise, and ended by answering questions, which included a segment discussing the importance of self-care for caregivers.

The conference closed with remarks from Markus Wartenberg, who thanked everyone who made the conference possible, and shared his hope that we will meet in person in 2021. Norman Scherzer, Executive Director of the Life Raft Group, had the last word, stating that we had unfinished business: “To assure that all GIST patients received mutational analysis for accurate diagnosis, and had access to the best possible treatment for their individual disease. May it be so.”

The conference ended on a high note. The final sessions had over 60 people in attendance, from 27 countries, the highest attendance for any New Horizons meeting.

The slidedecks and recordings of the sessions are available now on the SPAEN website.