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New Horizons GIST Meet 2016

I had the good fortune of attending the New Horizons GIST meet in Sitges, Barcelona Spain in May 18-21 2016.

It was a proud moment for me to represent FOM in the meet!  Also attending the meet from India was Viji Venkatesh  head of South east Asia for Max Foundation.

Sitges is a beautiful sea side town next to Barcelona, it was a great location for the conference.

The Conference was well organized by Mr. Markus Wartenberg and Ms Kathrin Schuster.

Mr. Markus welcomed all the participants and talked on the importance of management by GIST experts and insistence on Mutational analysis. He also talked about healthcare industry budgets, management of Non Kit/PDGFR GIST. Other topics covered by him included generic Imatinib, access to clinical trials and importance of compliance and striking a balance between efficacy of the drug and quality of life for the patient and the recent problem of non availability of Regorafenib in Germany due to some  policy decisions by Bayer Germany.

Dr Piotr Rutkowski from Poland talked about Localised GIST and its treatment. The following were the key points.

  • Diagnosis of GIST is done by CT scan, endoscopy and biopsy. Biopsy helps in confirming the disease and starting Neo-Adjuvant therapy.
  • Primary treatment of GIST is surgery, followed by adjuvant therapy and in some resistant cases by 2’nd and 3’rd line of drugs and maybe by new trials.
  • Principles of surgery include: Complete resection with negative margins, Non rupture of the tumour, Neo adjuvant therapy to avoid mutilating surgery, Frozen tissue for molecular testing, Laproscopic surgery if used should only be for small GIST.
  • Stratify the risk of recurrence of GIST to evaluate patient prognosis, use of adjuvant therapy and follow up schedule.
  • Major prognostic factors for resectable small GIST include tumor size, mitotic count, tumour site, rupture of tumour, Mutational status.
  • Adjuvant therapy duration varies upon type of tumor, surgery performed and risk classification.
  • In Recurrence: In exon 9 mutation give 800 mg Imatinib, other mutations start other suitable drugs, Recurrence after stopping Imatinib – restart Imatinib. Radiation Proton therapy for rectal GIST.
  • Important to differentiate between true and false progression.
  • Resection of focal progressive disease leads to lesser chances of recurrence.
  • Management of progressive disease involves increasing dose of imatinib, local surgery/RFA, second line Sunitinib, or drug trial.
  • In case of resistance to the drug check for compliance of the patient, check for genetic resistance ie type of mutation.

Key to efficacy in Sunitinib management is personalized dosing, management of side-effects and treatment duration.

Dr. Breelyn Wilky from USA spoke on Approach to progressive disease in GIST.

  • 3 types of progression: Limited, Nodular and Widespread.
  • Nodular progression is due to secondary mutation in that local area, rest of the tumour is well controlled with the drug. Treatment of this involves Surgical resection or RFA/ Embolization.

Widespread progression: check for patient compliance, do mutational analysis, consider re-biopsy then start medicines accordingly. Consider modifying dose.

Dr. Maria Rychter from Belgium spoke on Mutational analysis in GIST.

  • The concept of diagnostic markers and therapeutic targets.
  • 3 types of mutations: Kit(75%), PGDFRA(15%), Wild type.
  • KIT 65% exon 11, 8% exon 9.
  • Exon 11 Gastric are less aggressive tumours.
  • Exon 9 non gastric are aggressive tumours.
  • PGDFRA mutations gastric are less aggressive tumours.
  • Exon 11 responds very well to Imatinib.
  • Exon 9 you may require 800 mg of Imatinib.
  • Helps in determining which drug and dosage to give.
  • Reduces risk of unnecessary adjuvant therapy.

Dr. Sabrina Rossi from Italy spoke on Factors affecting success of Mutational analysis in GIST.

  • Stressed on the points that tissue blocks should not be too old when doing mutational analysis.

Dr. Breelyn Wilky spoke on Clinical trials in GIST.

  • Future of the GIST treatment will on the following: Improving KIT inhibitors, Novel targets for GIST, Combination approaches, Precision medicine and Immunotherapy.
  • Imatinib though the best drug for GIST can’t offer cure because of: persistence of viable cells, development of secondary resistance, non kit mutant gist.
  • Drugs used in trials are: Nilotinib, Masitinib, Dasatinib, Immunotherapy drugs, Regorafenib, sorafenib,pazopanib, ponatinib, famitinib,vatalanib,temsirolimus, everolimus, perifosine,BKM 120,BYL 719, trametinib, onalespib, auy922, BLU 285, ARO 002.
  • Important approaches in trials are: Improved targeting of KIT receptor and secondary mutations, target escape pathways, target other mechanisms in the cell.
  • Important to match the results of Mutational analysis to the drugs in the trial.

GIST subtypes, Molecular determined Therapy:

  • Type of mutation and the effective drug:
  • Kit exon 11- Imatinib 400 mg,
  • KIT exon 9- Imatinib 800 mg,
  • PDGFR D842V- (BLU- 285 or Crenolanib trial),
  • SDH-B deficiency- Sunitinib or Regorafenib.
  • Raf V600E , NF- 1 and Ras- Raf inhibitor,
  • P13K- P13K or mTOR inhibitor,
  • IGF overexpressed: IGF-1R inhibitor trial
  • Exon 13:Sunitinib,
  • Exon17: Regorafenib or Panotinib
  • TRK fusions:LOXO 101

Axitinib plus Pembrolizumab Immunotherapy,

Dasitinib plus ipilimumab Immunotherapy,

Nivolumab plus ipilimumab Immunotherapy

Intuvax plus Sunitinib Immunotherapy

Dr. Stefan Schonberg from Austria spoke on the Mitigate project.

Goal of the project is to develop novel protocols and guidelines to diagnose and treat patients with Metastatic GIST resistant to current treatment.

  1. Innovative strategies for biopsy, inline tissue analysis, MS fingerprinting- gives results of Mutational analysis in a few hours.
  2. Molecular tumour characterization
  3. PET and MRI imaging, developing a PET Scan which can show which drug the tumour is sensitive to.
  4. Assesment of bio distribution and dose calculation and measurement of therapeutic effectiveness.
  5. Minimal invasive treatment, including SIRT, Abalation and Robotic surgery.

Ms. Viji Venkatesh Head of South east Asia Max foundation spoke on The Indian Experience in GIST management.

She spoke on the challenges in India like low economics, illiteracy, lack of knowledge, difficulty of access to GIST specialist in rural areas and how Max foundation through its NOA program and educational meetings is connecting with the people of India.

She spoke on her own unique program of Chai for Cancer for fundraising which is doing very well in India and USA.

Her presentation was much appreciated and people applauded the work done by FOM for GIST awareness in India.

Dr. Bernd Kasper from Germany spoke Localized disease:

Stressed the importance of Mutational analysis and on adjuvant Imatinib in GIST.

Dr. Peter Reichardt from Germany spoke on Progressive disease:

  • Emphasised on the correct dose of Imatinib is important for disease control.
  • Focal progression: continue same drug and surgery for focal lesion.
  • Generalized progression: Increase dose of medicine or change to 2’nd line Sunitinib.
  • Before starting 3’rd line of drug, find out what dose of Sunitinib the patient was on and give individualized dosing and individualized wash out time.

3’rd line drug Regorafenib is not available in Germany due to company policy issues.

Dr. Sebastian Bauer spoke on Clinical trials in GIST:

  • Alternating Imatinib(400mg for 3 weeks) followed Regorafenib (160mg for 3weeks)to hit more targets to overcome resistance.
  • Rapid alternating Sunitinib and Regorafenib 3 days of 37.5 mg Sunitinib followed by 4 days of 120 mg Regorafenib.
  • Ponatinib trial.
  • Masitinib trial.
  • Pazopanib trial.
  • Cabozantinib trial.
  • Crenolanib trial.
  • BLU-285 (PDGFRA mutation and Exon 17 mutations) trial offering promising results.
  • DCC-2618 trial.
  • MEK 162 plus Imatinib trial.
  • Alpelisib plus Imatinib trial.
  • Dovitinib trial.
  • Immunotherapy trials in USA.
  • He emphasized about the importance of involvement of Patient advocate groups in these trials for better recruitment and better understanding of results.

Mr. Elias Pean of EMA talked on Generic Drugs  in Cancer:

  • Generic drug is defined as the drug having the same qualitative and quantitative composition in active substances as the Originator.
  • European Union has very stringent quality controls before any Generic drug is allowed in the market.
  • Some people expressed their comfort with the Original drug than Generic drugs.

Dr. Peter Reichardt spoke on Immuno-oncology:

  • Drugs for immune oncology have names ending with ‘mab’ standing for monoclonal antibody.
  • T cells and dendritic cells of the Immune system are very important in the killing of cancer cells.
  • GIST cells are not very mutated as compared to Melanoma whose cells are heavily mutated, hence Immunotherapy works better in Melanoma than GIST.
  • Immuno-therapy needs a longer time to act hence patient needs to be in a good condition.
  • This therapy is very expensive.
  • Trials are going on and it is too early to confirm the efficacy and practicality of this system.

In the patient Information and education- sharing best practice the following were the presentations:

  • David Josephy from Life raft group Canada shared his experiences.
  • Rodrigo Salas from Mexico talked on the South American experience in GIST management.
  • David Falconer from UK shared his views on the English aspect of GIST management and their web support to the patients.
  • Gerard from Netherland spoke on his ongoing unique software they are developing for GIST.
  • Gabriella from Italy spoke on the role of pharmacist in GIST drug delivery.
  • Ferdinand from Kenya spoke on the African experience including cancer as a taboo and lack of education and the efforts they are taking to eradicate these problems.
  • Myself spoke on “FOM and GIST awareness in India”, key points of my talk were:

Conducting regular meets , printing GIST education materials including my booklet on ‘Nutrition and Holistic way for living with GIST’. Patient counseling, Chai for Cancer initiative and advocacy work done for continued exemption on import tax for Glivec .

Talked on the challenges in India including access to correct information, GIST specialist doctors, compliance issues, myths and stigmas and economic problems. And how FOM by conducting regular meetings and network is helping eradicate these issues.

Conclusions:

  • It was a well-organized meeting with the top GIST specialist.
  • Imatinib remains the main drug of choice for treatment.
  • Surgery is the final curative for GIST.
  • Resistance if any should be carefully evaluated before changing over to another drug.
  • Re-biopsy should be done in cases of recurrence along with a new Mutational analysis to study change of mutation if any.
  • 2’nd and 3’rd line of drugs are effective but should be used with individualized dosing and careful management of toxicities.
  • Mutational analysis is a must in the diagnosis for GIST.
  • GIST specialist centers are important as GIST needs multidisciplinary team approach.
  • Compliance in taking the drug is very important.
  • Clinical drug trials including Immuno-Therapy trials are on across the world for resistant GIST offering hope.
  • Mitigate project in Europe is aiming to offer newer diagnostics and treatment options for resistant GIST cases.
  • It is important to network with various GIST support organizations across the world for better support and understanding of GIST.

New Horizons GIST Sitges Day 3-109

New Horizons GIST Sitges Day 2-216

Photos courtesy: Katherin Wermke

Report by Dr. Nikhil Guhagarkar- FOM Mumbai

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