Advances in Personalized Medicine and Improving the Quality of Life: The Future of Cancer Care


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Advances in Personalized Medicine and Improving the Quality of Life: The Future of Cancer Care

  1. 1. Advances in Personalized Medicine and Improving Quality-of-Life: The Future of Cancer Care Maurie Markman, M.D. Senior Vice President for Clinical Affairs Cancer Treatment Centers of America
  2. 2. Goals of Anti-Neoplastic Therapy• Maximize/improve overall survival (“cure”, if possible)• Treat and prevent (if possible) cancer-related symptoms• Delay the time to measurable and symptomatic progression of the disease process• Maximize overall quality-of-life (including the impact of the cancer, its therapy, and highly relevant psychological/emotional factors) 2 © 2011 Rising Tide
  3. 3. Relevance of Quality-of-Life toCancer Survival• Staren ED, et al, The Breast Journal 2011• 1,511 breast cancer patients (analytic and non- analytic) treated at Cancer Treatment Centers of America (1/01 – 12/08)• Mean age at presentation 52.5• Median overall survival 32.8 months• EORTC-C30 survey instrument• QOL scores at presentation predictive of survival, particularly role function, independent of tumor stage. 3 © 2011 Rising Tide
  4. 4. Relevance of Quality-of-Life toCancer Survival• Braun D, et al. BMC Cancer 2011• 1,194 lung cancer patients (analytic and non- analytic) treated at Cancer Treatment Centers of America (1/01 to 12/08)• EORTC-C30• Every 10-point increase in “physical function” predicted for a 10% increase in survival• Every 10-point increase in “global QOL” associated with 9% increase in survival 4 © 2011 Rising Tide
  5. 5. Relevance of Quality-of-Life toCancer Survival• Braun D, et al. Health and Quality of Life Outcomes 2011• 396 patients stages III-IV colorectal cancer treated at Cancer Treatment Centers of America, followed for a minimum of 3 months• Appetite loss and global health at baseline strongly correlates with survival• Improved physical functioning at 3 months correlates with a superior survival outcome 5 © 2011 Rising Tide
  6. 6. “Targeted”, “Personalized”, or(most recently) “Precision” therapy• Not a new concept• Hormonal therapy of breast/prostate cancer: Earliest systemic anti-neoplastic strategy ER receptor discovered 40 years ago• HER-2 over-expression in breast cancer• CML/GIST (profoundly different pathology but similar molecular abnormalities resulting in essentially identical highly effective therapy)• Resulting over-simplification of complex biology 6 © 2011 Rising Tide
  7. 7. EGFR (Epidermal Growth FactorReceptor)• Major research efforts to develop EGFR receptor inhibitors, known in pre-clinical systems to be relevant in tumor progression• Majority of lung cancer patients over-express EGFR receptor• 10% of patients with metastatic lung cancer major response to one EGFR inhibitor• Phase 3 randomized trials with this agent (combined with chemotherapy) negative 7 © 2011 Rising Tide
  8. 8. EGFR Receptor• Evidence that over-expression of receptor in lung cancer is not clinically relevant, but the presence of particular EGRF mutations predict for clinical activity (approximately 20-25% of patients - more commonly observed in non- smokers, Asian population, women)• Definitive evidence lung cancer patients with a mutation experience a superior outcome when treated with EGFR inhibitor alone, rather than chemotherapy (Lancet Oncology 2012; 13:239) 8 © 2011 Rising Tide
  9. 9. Other Examples of Effective“Precision” Therapy• ALK rearrangement (4-5% of lung cancer) – Crizotinib - FDA approved 8/2011• BRAF mutation (50% patients with melanoma) – Vemurafinib – FDA approved 8/2011• Hedgehog pathway inhibitor (basal cell carcinoma – locally advanced/metastatic) – Vismodegib – FDA approved 1/2012• PARP inhibitor (5-10% of ovarian cancer patients with BRCA1 or 2 abnormalities) 9 © 2011 Rising Tide
  10. 10. Issues for Future “PrecisionMedicine” Drug Development• Small subsets of patients: How does one prove clinical benefit? Is a phase 3 randomized trial always required? How does a drug achieve FDA approval?• Quality of evidence for clinical utility of molecular/biological markers (e.g., individual/ institutional financial conflict-of-interest)• Insurers willingness to pay for anti-neoplastic therapy based on molecular test results, rather than on data from phase 3 randomized trials? 10 © 2011 Rising Tide
  11. 11. But ….• The future is here• Within the next year it will be possible to sequence the entire genome of a tumor and the corresponding normal genome of an individual cancer patient for < $3,000 (12-15 years ago this would have cost $6,000,000,000)• So, the issue is not whether the data will be available to patients, but rather how to optimally convert this massive quantity of raw data into information of genuine value in individual patient management 11 © 2011 Rising Tide
  12. 12. Declining Cost ofSequencing a Human Genome 12 © 2011 Rising Tide
  13. 13. “The STEPS”• Discovering the “code” in an individual patient– (“sequencing”) (easy)• Attempting to break the “code” – (“bio- informatics) (difficult - extremely difficult)• Exploring the relevance of the proposed solution (“clinical validation with a targeted therapeutic”) (unknown difficulty) –• Proving the relevance of the solution (“N of 1” research) (soon-to-be the new paradigm in clinical cancer therapeutic research) 13 © 2011 Rising Tide
  14. 14. This future of cancer medicine is veryreal and is today ….• Bergethon K, et al (+ 22 other authors) ROS1 rearrangements define a unique molecular class of lung cancers. Journal of Clinical Oncology 2012; 30(8):863-870.• Recently described molecular abnormality• In vitro studies revealed cancer cells with this abnormality respond to crizotinib (“FDA approved ALK rearrangements in lung cancer”)• 1,073 lung cancer patients screened 1.7% with abnormality (Less than 1 in 50 patients) 14 © 2011 Rising Tide
  15. 15. This future of cancer medicine is veryreal and is today ….• (page 867) “The patient is a 31-year old male never-smoker diagnosed with multifocal bronchiolalveolar carcinoma in August 2010. Genetic testing of his tumor demonstrated no EGFR mutation or ALK rearrangement. He was treated at an outside institution with first-line erlotinib with no response. As a result of progressively worsening symptoms and hypoxia, he was referred to MGH for additional genetic testing and was found to be ROS1 positive.” 15 © 2011 Rising Tide
  16. 16. This future of cancer medicine is veryreal and is today ….• “On August 20, 2011, the patient was started on crizotinib at the standard dose of 250 mg twice daily. In less than 1 week, he noted a significant improvement in symptoms, and by 2 weeks, his hypoxia had resolved. Restaging scans at 8 weeks demonstrated near complete resolution of his multifocal lung tumor, which was subsequently confirmed at 12 weeks. At the time of this report (6 months), the patient continues on crizotinib with no evidence of recurrence.” 16 © 2011 Rising Tide
  17. 17. This future of cancer medicine is veryreal and is today ….• “This case suggests that patients with ROS- positive non-small cell lung cancer may be exquisitely sensitive to therapeutic ROS1 inhibition”• N of 1 17 © 2011 Rising Tide