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

Explore the benefits and challenges of treating elderly patients with metastatic NSCLC, debunking common misconceptions and discussing the use of chemotherapy to alleviate cancer symptoms. Learn about ongoing clinical trials and the importance of tailored treatment regimens. Stay informed on survival rates, side effects, and supportive care for elderly lung cancer patients.

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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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