Targeted Therapies in Lung Cancer Patient Forum

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1 Targeted Therapies in Lung Cancer Patient Forum

2 Welcome! What to expect today Experts in EGFR, ALK, ROS1, BRAF, MET, and RET+ lung cancers will be presenting and interacting with patients and caregivers. General session starts now and goes until noon with a 30 minute break at 10am. Breakout sessions will run from 1-2:30, check your agenda for room numbers. Break afterward until 2:50. Second general session runs from 2:50-4pm here. Find and ask questions of faculty during the breaks and at lunch! No webcast during breaks and lunch.

3 To ask a question: Please write questions for faculty down on index cards or them to us. General Sessions: targetedtherapy@cancergrace.org Breakout Sessions: ALKROS1@cancerGRACE.org EGFR@cancerGRACE.org METRETBRAF@cancerGRACE.org 3

4 The Many Faces of Progression Nathan Pennell, MD, PhD Cleveland Clinic Taussig Cancer Institute

5 The Face of Lung Cancer is Changing

6 The Face of Progression is also Targeted therapies can be quite effective, BUT Changing! Targeted therapies for metastatic lung cancer are not cures, and most patients eventually have their cancer worsen ( progression in oncology-speak) Janus the 2-faced Roman god of beginnings, endings and transitions 6

7 Progression is not one-size-fits-all! The approach to the patient with acquired resistance to a targeted therapy needs to be individualized to their specific situation 1. Generalized progression (worsening everywhere) 2. Slow (indolent) progression 3. Progression only in 1 (or a few) sites 4. Progression only in the brain 7

8 Generalized (or Traditional) Progression Best response 6 months later 8

9 Generalized Progression Therapy is not working any more and needs to be changed! Rebiopsy to help guide therapy? Switch to next-generation drug? Switch to alternate therapy (e.g. chemotherapy, clinical trial)? 9

10 ALK+ pt progressed on 1 st /2 nd line TKI: Carbo, pemetrexed and bevacizumab December 2012 March 2013 Lasted 18 months, longer than crizotinib or ceritinib!

11 Is this Progression? Best response 16.3mm 12 months later 18.2mm CT Report: Progression of liver metastases 11

12 Indolent (Slow) Progression Don t be in a rush to change something that may still be helping! Some cancer with AR (like T790M+) can be relatively slow growing Patients can be safely observed on current therapy sometimes for many months 12

13 62 year old woman with EGFR mutation+ adenocarcinoma Presentation 2 months later on Tarceva 18.2mm 13

14 62 year old woman with EGFR mutation+ adenocarcinoma Most recent scan 16.3mm 6 months earlier 18.2mm 14

15

16 Treatment of lung cancer is a marathon and not a sprint! 16

17 Oligoprogression (Progression in 1 or a few sites) After 3 months on Tarceva New Solitary Liver Lesion 10/2016 after 18 months on Tarceva 17

18 Oligoprogression DON T OVERTHINK IT Biopsy studies have shown that each metastasis can independently develop its own mechanism of AR which may not be in other sites Weeding the garden can allow patients to continue therapy for many months before needing to change But need to be careful about definition of oligo! 18

19 Oligoprogression New Solitary Liver Lesion 10/2016 after 18 months on Tarceva Post-SBRT 4/2017, still on Tarceva 19

20 CNS-Only Progression In September 2016 after 10 months on afatinib, patient had a seizure CT scans showed no progression outside the brain The patient, a 31 year old man, did not want whole brain radiation 20

21 CNS-Only Progression Most drugs do not have the same penetration into the brain as the rest of the body The cancer itself may still be sensitive but the drug just can t reach it Radiation to the brain while continuing drug may be an option (like in oligoprogression option) Switching to a newer drug with better CNS penetration may also help 21

22 CNS-active drugs may be the best answer (Tagrisso) (Iressa) Ballard et al., Clin Cancer Res

23 CNS-Only Progression September 2016 after 10 months on afatinib September 2017 on osimertinib 23

24 Treatment of lung cancer is a marathon and not a sprint! 24

25 Progression has as many faces as the patients with lung cancer Acquired resistance is not the end but only the beginning of the next step The approach to progression must be individualized between patient and doctor New drugs, safer local treatments have dramatically changed how we manage patients with disease progression 25

26 Thank You! 26

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