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The use of systemic anti-cancer therapy for elderly patients with metastatic NSCLC

The use of systemic anti-cancer therapy for elderly patients with metastatic NSCLC. Jared Weiss, MD University of North Carolina 11/14/2014. What is the median age of presentation of NSCLC?. 40 50 60 70 80 90. Median age at diagnosis: 71.

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The use of systemic anti-cancer therapy for elderly patients with metastatic NSCLC

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  1. The use of systemic anti-cancer therapy for elderly patients with metastatic NSCLC Jared Weiss, MD University of North Carolina 11/14/2014

  2. What is the median age of presentation of NSCLC? • 40 • 50 • 60 • 70 • 80 • 90

  3. Median ageat diagnosis: 71 Incidence of NSCLC in the US by age at diagnosis No. of patients Age at diagnosis (y) Data from SEER Cancer Statistics Review, 1975-2001.

  4. The elderly are untreated…badly • Misperceptions about expected longevity of the elderly • Misperceptions about tolerability of treatments in the elderly • Misperceptions about efficacy of treatments in the elderly

  5. What is the life expectancy of a 70 year old man? How about a 70 year old woman? • Man 2 years, Woman 3 years • Man 5 years, Woman 7 years • Man 10 years, Woman 12 years • Man 12 years, Woman 14 years • Man 14 years, Woman 16 years

  6. The elderly: In the absence of severe comorbidity, life expectancy is likely driven by the lung cancer SSA acturial life table, cited in Weiss, 2013

  7. “Traditional” view of Quality of Life • Chemo causes: • Nausea • Alopecia • Fatigue • Infections • Therefor, maximize quality of life by avoiding chemo.

  8. An Alternative View of Quality of Life Cancer growth causes: *Pain *Cough *Shortness of breath *Fatigue *Organ Failure *Thrombosis *Hoarse voice *Nausea *Anorexia Chemo can alleviate cancer suffering. Better drugs and better supportive care means more tolerable anti-cancer therapy. Symptoms of progressive cancer Side-effects of therapy

  9. ELVIS: Chemo works in the elderly Vinorelbine 30 mg/m2 days 1 & 8 every 21 days vs supportive care 1-year Survival 14% vs 32% Favorable QoL Overall ELVIS Group. J Natl Cancer Inst. 1999;91:66-72.

  10. Issues in 1st line chemotherapy • Two drugs vs. one • Bevacizumab (Avastin) • Molecular options • Elderly-specific chemo? • Poor PS patients

  11. Timeline for Chemo (Every regimen is different; just basic idea here) Regimen 2: Partner drug +/- Biologic Observe with imaging until progression Treat to 4-6 cycles PR or SD Maintenance chemotherapy: 1. Stop carboplatin 2. Continue partner +/- biologic or Just partner or Just biologic or New drug (pemetrexed or erlotinib) Regimen 1: Carboplatin + Partner drug +/- Biologic X 2-3 cycles (cycle is three weeks in most regimens so 6-9 weeks Imaging PD Change chemo: Carboplatin + Different partner +/- Biologic PR: Partial response SD: Stable disease PD: Progressive disease

  12. Overall Survival and Progression-free survival in IFCT-0501 Trial OS PFS HR 0.64 (95% CI 0.52-0.78, p<0.0001) HR 0.51 (95% CI 0.42-0.62, p<0.0001) Quoix E, et al. Lancet. 2011;378:1079-1088.

  13. Trial Design 1:1 RANDO M IZ A T I O N Pemetrexed 500 mg/m2 IV Q3W • Eligibility: • Stage IIIB/IV NSCLC • (malignant effusion) • ECOG PS 2 • No prior chemotherapy • Stable CNS disease • Measurable disease • Adequate organ function • (including GFR≥ 45 ml/min) • Signed informed consent Arm A • Stratification factors: • Stage: IIIB vs IV • Age: ≥70 vs <70 • Wt loss: ≥5% vs <5% X 4 cycles Pemetrexed 500 mg/m2 IV Q3W + Carboplatin AUC 5 IV Q3W n=137* Arm B • Primary endpoint: • Overall Survival Secondary endpoints: • Progression-free survival • Overall response ate • Safety Pre-medications: • Vitamin B12: 1mg IM Injection • Folic Acid: 350-1,000mcg po daily • Dexamethasone 4mg po BID the day • before, the day of, and the day after Median age: 65 in both groups >70 years: 35.2% in pemetrexed group 36.8% in pemetrexed + carbo group 5

  14. Overall Survival—PS2 trial mOS 9.1 vs. 5.6m HR=0.57 (0.41-0.79) p=.001 Pem + Carbo Pem alone Lilenbaum, ASCO 2012, Abstr 7506

  15. Overall Survival, elderly subset from PS2 trial Lilenbaum, ASCO 2012, Abstr 7506

  16. Carbo/paclitaxel vs. Carbo/Nab-paclitaxel Albumin-bound paclitaxel 100 mg/m2 d1, 8, 15 Carboplatin AUC 6 d1 21 Day Cycles No Premedication Stage IIIb/IV NSCLC No prior therapy for metastatic disease PS 0-1 N = 1,050 1:1 Paclitaxel 200 mg/m2 d1 Carboplatin AUC 6 d1 21 Day Cycles With Premedication of Dexamethasone + Antihistamines Patients had no active brain metastases or ≥ grade 2 neuropathy at baseline Socinski, et al. 2010 ASCO LBA7511

  17. Carbo/paclitaxel vs. Carbo/Nab-paclitaxel Socinski, et al. JCO 30:17, 2012

  18. Overall Survival ab-P/C P/C * Subgroup analyses exploratory in nature Socinski et al, ASCO 2011, Abstr 7551

  19. Ongoing Second Line Phase II trial (LCCC1210) • Sites: • UNC • Cleveland Clinic • Upitt • Highlands Oncology • Rex Hospital • Fox Chase • Swedish Cancer Institute • Bon Secours • Inclusion: • At least 70 years of age • Prior non-taxane doublet • 1 targeted agent allowed if mutation + • PS0-2 • Adequate end-organ fxn (relatively liberal criteria) NCT01702844

  20. Randomized Phase II First Line Trial Carboplatin AUC 6 D1 Nab-paclitaxel 100mg/m2 D1, 8, 15 Randomization Carboplatin AUC 6 D1 Nab-paclitaxel 100 mg/m2 D1, 8 • Inclusion • 1st line NSCLC • At least 70 years of age NCT02151149

  21. CDDP/Pem vs. CDDP/Gem elderly data (Nonsquamous patients) HR OS (all favor pem): Subgroup <65: .89 Subgroup >65: .75 Subgroup <70: .83 Subgroup >70: .85 Gridelli et al, Clinical Lung Cancer, 13:5, 2012.

  22. JMEN elderly data: Pem vs. placebo HR OS (all favor pem): Subgroup <65: .62 Subgroup >65: .87 Subgroup <70: .63 Subgroup >70: .81 Gridelli et al, Clinical Lung Cancer, 13:5, 2012.

  23. Treatment Scheme of ECOG 4599 R A N D O M I Z E Carboplatin (AUC 6) Paclitaxel 200 mg/m2 Bevacizumab 15 mg/kg* Non-squamous NSCLC Absence of brain metastasis ECOG PS 0 or 1 Informed consent Carboplatin (AUC 6) Paclitaxel 200 mg/m2 * Bevacizumab continued as monotherapy for CR/PR/SD after 6 cycles Ramalingam, JCO 26:1, 2008

  24. Efficacy of bevacizumab in Elderly in E4599 (carbo/paclitaxel +/- bev) PFS OS mOS 12.1 PC, 11.3 PCB, HR .87 mPFS 4.5PC, 5.9m PCB, HR .76, p.063 Ramalingam, JCO 26:1, 2008

  25. Pem vs doce elderly Hanna data: OS <70 years HR 1.02 Pem 7.8m Doce 8m >70 years HR .86 Pem 9.5m Doce 7.7m Weiss et al, JCO 24:27, 2008.

  26. Specific Drugs in Elderly Lung CA Weiss, Expert Rev. Anticancer Ther. 12:1, 2012.

  27. 6 FEB 2002 11 FEB 2002

  28. 2009 Perspective Mok, NJEM 2009

  29. Crizotinib vs Standard Chemotherapy in ALK+ NSCLC (PROFILE 1007): PFS in 2nd or 3rd Line 100 80 60 Probability of Survival Without Progression (%) 40 20 0 0 5 10 15 20 25 Mos Pts at Risk, nCrizotinibChemotherapy 173174 9349 3815 114 21 00 Shaw AT, et al. N Engl J Med. 2013;368:2385-2394.

  30. PROFILE 1014: Crizotinib vs Pemetrexed/ Platinum in Advanced Untreated NSCLC Adv ALK-pos nonsquamous NSCLC not previously treated(N = 343) Crizotinib 250 mg BID Primary endpoint: PFS Pemetrexed + Cisplatin or Carboplatinq3w x 6 cycles 100 80 60 40 20 PFS (%) 0 0 5 10 15 20 25 30 35 Solomon BJ, et al. N Engl J Med. 2014;371:2167-2177. Mok T, et al. ASCO 2014. Abstract 8002.

  31. Nivolumab in SqCC Lung Brahmer, NEJM 2015

  32. Nivolumab in non-SqCC NSCLC Paz-Ares ASCO 2015

  33. Toxicity of PD1 Brahmer, NEJM 2015

  34. THANK YOU! For more information: www.cancergrace.org For advocacy: www.lungcancerinitiativenc.org

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