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Acquired Resistance Patient Forum

Life After Erlotinib : What Next?. Jared Weiss Vice President, Cancergrace Assistant Professor of Medicine, UNC Lineberger Comprehensive Cancer Center. Acquired Resistance Patient Forum. In ALK, ROS1 & EGFR Lung Cancers. September 6, 2014 | Boston.

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Acquired Resistance Patient Forum

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  1. Life After Erlotinib: What Next? Jared Weiss Vice President, Cancergrace Assistant Professor of Medicine, UNC Lineberger Comprehensive Cancer Center Acquired Resistance Patient Forum In ALK, ROS1 & EGFR Lung Cancers September 6, 2014 | Boston

  2. Yesterday’s victory is today’s challenge EGFR mutation positive Gefitinib(n=132)Carboplatin/paclitaxel (n=129) 2009 Perspective: 10 months PFS without chemo! 1.0 0.8 0.6 Probability of progression-free survival 2014 Perspective: Only 10 months? Now what? 0.4 0.2 0.0 0 4 8 12 16 20 24 Months Patients at risk : Gefitinib 132 108 31 11 3 0 71 C/P 129 103 37 7 2 1 0

  3. Crizotinib for ALK: Like erlotinib for EGFR, better than chemo, but again, now what should be done? Mok, ASCO 2014

  4. Option 1: Learn from the politicians

  5. When this is a good idea Amount of Cancer Time West, ASCO 2013

  6. Now it’s time for a new idea Amount of Cancer Time West, ASCO 2013

  7. Baseline: Start TKI 3m: Response 14m: RECIST PD 45 18m 24m 30m 35m 37m: Stop TKI 39m: First dyspnea Oxnard, ASCO 2012 and Santa Monica Lung 2014

  8. R R S S R R R S R R R S EGFR TKI beyond RECIST • 42 pts with EGFR-mutant lung cancer receiving 1st-line erlotinib on 3 clinical trials • 45% of pts could delay change of therapy >3 months after RECIST progression • 21% delayed treatment change >12 months Oxnard et al, ASCO, 2012 and Santa Monica Lung 2014

  9. Crizotinib past progression Acquired Resistance Patient Forum | Sept. 6, 2014 | Boston Ou, Annals of Oncology 2014

  10. Option 2: Weeding the garden

  11. When weeding is a good idea PD-Subtype Systemic-PD Oligo-PD CNS-PD (Sanctuary) Slightly adapted from Gandara, CLC 2013

  12. Why radiation can be a good way to weed In vitro In vivo Das, AACR 2006. Das, AACR 2007. Mak, The Oncologist, 2011

  13. It has been tried: MSKCC experience, all EGFR (n=18) Yu, JTO 2013

  14. U Colorado Experience: Mixed EGFR (n=27) and ALK (n=38) Weickhardt, JTO 2012

  15. Ongoing Trial: LCCC1123: Prospective Phase II • Collaborators: • Cleveland Clinic • UPMC • U. Colorado • UCSF • Swedish • FCCC • Yale U. • ECU • UNC Primary endpoint: PFS after SRS Secondary endpoints: LCR of ablated lesions, mOS from initiation of SRS, QOL as measured by FACT-L, attributable toxicity, serum-based biocorrelates (Veristrast) PI: Jared Weiss

  16. Flare Reaction: The Danger of Coming off of EGFR TKI at progression Last day of TKI Off EGFR TKI Resumed TKI Day 0 Day 21 Day 42 Chaft…Riely CCR 2011

  17. Case studies describe the same phenomenon with ALK Disease well controlled Flare 15 days After stopping crizotinib Pop JTO 2012

  18. Third option: Keep the TKI going with the new chemo Chemo alone Chemo + erlotinib 18% RR 41% RR Goldberg et al, Oncologist, 2013

  19. But, no advantage for PFS or OS Platinum-based combination chemotherapy One drug chemotherapy Goldberg, Oncologist 2013 Acquired Resistance Patient Forum | Sept. 6, 2014 | Boston

  20. And, there is a toxicity cost Acquired Resistance Patient Forum | Sept. 6, 2014 | Boston Herbst, JCO 2005 (TRIBUTE data)

  21. Chemotherapy +/- Ongoing EGFR TKI for Acquired Resistance: IMPRESS Trial IMPRESS TRIAL PI: Tony Mok & Jean-Charles Soria Activating EGFR mutation Progression on gefitinib No prior chemotherapy N = 250 Cisplatin/Pemetrexed R A N D Cisplatin/Pemetrexed + ongoing gefitinib Primary endpoint: progression-free survival

  22. Chemotherapy +/- Ongoing EGFR TKI for Acquired Resistance: Vanderbilt Trial Caboplatin / pemetrexed with erlotinib PD EGFR-mutant lung cancer with acquired resistance to erlotinib R Carboplatin / pemetrexed PD PI: Leora Horn, VICC

  23. When chemo used, it’s worth coming back to TKI later Heon, ASCO 2012 Hata, ASCO 2012 Acquired Resistance Patient Forum | Sept. 6, 2014 | Boston

  24. Systemic options other than chemo: Combination trials and 3rd generation TKIs • 3rd generation TKIs: CO1686, AZD9291, HM61713, EGFR816, ASP8273: Look promising, but most requires repeat biopsy (more on this in next talk from Dr. Sequist). More on 3rd gen TKI from Dr. PasiJanne in afternoon breakout session • Combination trials: Afatinib/cetuximab farthest along; AUY922/erlotinib, MET inhibitor/EGFR TKI, others. More on combo trials from Dr. Melissa Johnson at afternoon breakout session) • Other trials: Any active agent can be considered including immunotherapy. Acquired Resistance Patient Forum | Sept. 6, 2014 | Boston

  25. Options, summarized • Kick the can down the road • Local ablation of spots that are growing then restart TKI • Chemo + TKI • Chemo alone (but, must start quickly after stopping TKI and reconsider TKI later) • Combination Therapies • 3rd Generation TKIs • Other clinical trials

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