Lung cancer in the elderly D. Schrijvers, MD, PhD Ziekenhuisnetwerk - - PowerPoint PPT Presentation

Lung cancer in the elderly

• D. Schrijvers, MD, PhD

Ziekenhuisnetwerk Antwerpen(ZNA)-Middelheim Antwerp Belgium

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I ncidence and m ortality of all cancers and lung cancer in relation to age and gender ( US)

10,000 20,000 30,000 40,000 50,000 30- 34 35- 39 40- 44 45- 49 50- 54 55- 59 60- 64 65- 69 70- 74 75- 79 80- 84 Age category (years) Number of patients All-male Lung cancer-male All-women Lung cancer-women

National Program of Cancer Registries (NPCR) 2004

20,000 40,000 60,000 80,000 100,000 120,000 35- 39 40- 44 45- 49 50- 54 55- 59 60- 64 65- 69 70- 74 75- 79 80- 84 85+ Age category (years) Number of patients All-male Lung cancer-male All-women Lung cancer-women

Incidence Mortality

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Early-stage non-sm all cell lung cancer

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Surgery

Author ( year) N° pts Stage Positive prognostic factors Outcom e ~ Age Chang (07) 10.761 IA Tumor size (< 2.0 cm) 5-year survival Gender (women) 52 vs. 65% Age (< 67 years) Resection (anatomical) Ou (07) 19.702 IA-IB Age Gender (women) Socio-economic class Surgical treatment Histological differentation Tumor size (< 4 cm) (IB) Anatomical location (IB) Schneider (08) 2.021 NA ECOG PS Operative mortality 3.0% < 65 years 7.9% 65-75 years 10.5% > 75 years 5-year survival =

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Radiotherapy

Treatm ent Overall survival ( % ) No 6–14 (5-year) Conventional RT 34 (3-year) Stereotactic RT 70 (5-year)

Haasbeek CJ et al. Oncologist 2008

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Adjuvant cisplatin-based chem otherapy

Trial ALPI ANI TA BLT I ALT JBR.1 0 N° patients 1.101* 840 307 1.867 482 Eligibility Stage I-IIIA IB-IIIA I-III I-III IB-II Upper age limit None 75 None 75 None Total cisplatin dose (mg/ m² ) 300 400 240/ 150 300-400 400 + vinorelbine No Yes Yes Yes Yes + other agents Yes No Yes Yes No Hazard ratio 0.95 0.8 1.02 0.86 0.69 p .59 .02 .9 < .03 .04 Difference at 5 years (% ) No 8.6 No 4.1 15 * 1,209, minus 108 excluded from one center

Fruh M et al. J Clin Oncol 2008

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Adjuvant cisplatin-based chem otherapy:

• verall survival by treatm ent and age

Fruh M et al. J Clin Oncol 2008 HR death 0.86; 95% CI 0.78-94 HR death 0.90; 95% CI 0.70-1.16

All Elderly > 7 0 years

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Early-stage NSCLC in elderly patients

› Surgery › = standard of care › Feasible › Higher operative mortality in case of co-morbidity › Radiotherapy › Valuable option in selected patients › Adjuvant chem otherapy › No survival benefit > 70 years

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Advanced non-sm all cell lung cancer

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First-line treatm ent: com parison young- elderly

Author ( year) Treatm ent RR( % ) MOS ( m onths) Qol/ Tox Y E Y E Kelly (2001) Pacli-carbo NR NR 8.6 6.9 = Vino-cis Langer (2002) Pacli-carbo + G-CSF 22 23 9.1 8.5 > hemato Eto+ cis Schiller (2002) Pacli + cis 22.1 24.5 8.15 8.24 > grade 4 tox Gem + cis Doc + cis Pacli + carbo Lilenbaum (2005) Pacli 15 21 6.8 5.8 Pacli + carbo 28 36 9 8 Sandler (2005) Pacli + carbo 15 28.7 10.3 12.1 > tox with bev Pacli + carbo + bev 35 17.3 12.3 11.3

RR: response rate; MOS: median overall survival; Qol: quality of life; Tox: toxicity; Carbo: carboplatin; Pacli: paclitaxel; Cis: cisplatin; Bev: bevacizumab; Eto: etoposide; G-CSF: granulocyte-colony stimulating factor; Eto: etoposide; Gem: gemcitabine, Doc: docetaxel, Y: younger: E: elderly; NR: not reported

Avery et al. Cancer Treat Rev 2009

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First-line treatm ent in elderly patients: single agent

Author ( year) Treatm ent N pts RR( % ) MOS ( w ks) Qol/ Toxicity Elvis (99) BSC 78 21  Vino Vino 76 20 28 Kudoh (06) Vino 91 10 57

 D

Doc 91 23 39 Lilenbaum (07) Doc q 1w x3 q28 56 14 3 wks > w Doc q 3 wks 55 25 Leong (07) Gem 43 16 = Vino 45 20 Doc 46 22

RR: response rate; MOS: median overall survival; wks: weeks; Qol: quality of life: BSC: best supportive care; Vino: vinorelbine; Doc: docetaxel; Gem: gemcitabine; : better than; = : equal to; > more toxic than

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First-line treatm ent in elderly patients: com binations

Author ( year) Treatm ent N pts RR( % ) MOS ( w ks) Qol/ Toxicity Frasci (00) Vino 60 15 18  Vino + Gem Vino+ Gem 60 22 29 Gridelli (03) Vino 223 18 36 = Gem 223 16 28 Vino+ Gem 232 21 30 Comella (04) Gem + Pacli 65 32 9.2 mo = Gem + Vino 68 23 9.7 mo Pacli 63 13 6.4 mo Gem 68 18 5.1 mo Hainsworth (07) Doc 345 20 = Doc + Gem 22 Gridelli (07) Pem 44 4.5 18 = Pem + Gem 43 11.6 23

RR: response rate; MOS: median overall survival; wks: weeks; Qol: quality of life: Vino: vinorelbine; Gem: gemcitabine; Doc: docetaxel; Pem: pemetrexed; : better with; = : equal to: > more toxic; mo: months

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First-line treatm ent in elderly patients: platinum com pounds/ targeted agents

Author ( year) Treatm ent N pts RR( % ) MOS ( w ks) QolToxicity Chen (06) Carbo + Pacli 40 40 41 Cis > Carbo Cis + Pacli 41 39 42 Ramalingam (08) Carbo + Pacli 113 17 49  B Carbo + Pacli + B 111 29 45 Reck (09) Cis + Gem 112 20 NA  B Cis + Gem + B 192 30-34* NA

RR: response rate; MOS: median overall survival; wks: weeks; Qol: quality of life: Carbo: carboplatin; Pacli: paclitaxel; Cis: cisplatin; Gem: Gemcitabine; B: bevacizumab;  : worse with: > more toxic

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Second-line treatm ent in elderly patients

Author ( year) Treatm ent N pts RR( % ) MOS ( w ks) Qol/ Toxicity Wheatley (08) Erlotinib 112 7.6 31  E Placebo 51 NA 20

RR: response rate; MOS: median overall survival; wks: weeks; Qol: quality of life: E: erlotinib: paclitaxel; Cis: cisplatin;  : higher than

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Advanced NSCLC in elderly patients

› First-line chem otherapy › Single-agent vinorelbine, gemcitabine, or taxanes (paclitaxel and docetaxel) are first-line treatment options › Non-platinum combinations vs single agent

› Higher response rates and/ or disease-free survival › Sim ilar m edian overall survival or 1 -year survival rates › Slightly m ore toxic

› Platinum combinations

› Cisplatin m ore toxic than carboplatin

› Targeted agents

› Bevacizum ab m ore toxic

› Second-line chem otherapy › Targeted agents are treatment option

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Sm all cell lung cancer: lim ited disease

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First-line treatm ent

Author ( year) Age N°pts Treatm ent MST 5 YS p ( years) ( m onths) ( % ) Siu (96) < 70 580 CAV/ PE + RT 8 NS > 70 88 11 Jara (99) < 70 20 PE + RT 12.3 NS > 70 12 14.9 Yuen (00) < 70 271 PE + either BID/ QD RT 19 NS > 70 50 16 Ludbrook (03) < 65 55 CT + RT 37* .003 > 65–74 76 22* > 75 43 19* Schild (04) < 70 209 PE + either BID/ QD RT 22 NS > 70 54 17

BID: twice-daily; CAV: cyclophosphamide + doxorubicin + vincristine; CT: chemotherapy; HDEP: high- dose epirubicin + cisplatin; MST: median survival time; NS: not significant; PE: cisplatin + etoposide; QD:

• nce-daily; RT = radiotherapy; * : 2-year survival, 5YS: 5-year survival

Rossi A et al. Oncologist 2005

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First-line treatm ent: chem oradiation

Author ( year) Age N°pts Treatm ent RR MST ( years) ( % ) ( m onths) Murray (98) > 70 55 CAV (1 cycle) + PE (1 cycle) 89 12.6 20–30 Gy Jeremic (98) 72 72 cPE (2 cycles) 75 15 45 ACC HFX

ACC HFX = accelerated hyperfractionated radiotherapy; CAV = cyclophosphamide + doxorubicin + vincristine; cPE = carboplatin + oral etoposide; RR: response rate; MST = medial survival time; PE = cisplatin + etoposide Rossi A et al. Oncologist 2005

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First-line treatm ent: chem oradiation

› Role of thoracic irradiation › 13 randomized trials › 2140 patients

› 3 -year survival › 8.9 % CT alone › 14.3% CT+ RT › Relative risk of death › < 55 years: 0.72 (95% CI 0.56-0.93) › > 70 years: 1.07 (95% CI 0.70-1.64)

Pignon et al. N Engl J Med 1992

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First-line treatm ent: single agent

Author ( year) Age N°pts Treatm ent RR MST ( years) ( % ) ( m onths) Smit (89) > 70 13 Oral etoposide 84 16 Bork (97) > 70 32 Oral etoposide 7 30 Oral etoposide 7.5 Quoix (92) > 70 18 Epirubicin 50 Cerny (88) > 70 16 Teniposide 37.5 7.5 Tummarello (92) > 70 13 Teniposide 61 10 Cascinu (97) > 65 12 Teniposide 30 8

MST = median survival time; NR = not reported; RR = response rate Rossi A et al. Oncologist 2005

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First-line treatm ent: carboplatin com binations

Author ( year) Age N°pts Treatm ent RR MST ( years) ( % ) ( m onths) Evans (95) > 65 11 carbo + etoa 88 12.2 Matsui (98) > 70 16 carbo + etoa 93 15.1 Okamoto (99) > 70 16 carbo + eto 63 11.6 Goss (91) > 60 17 carbo + teni 72

a: oral etoposide; carbo: carboplatin; eto: etoposide; RR: response rate; MST = median

survival time; teni: teniposide

Rossi A et al. Oncologist 2005

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First-line treatm ent: single agent versus com binations

Study ( year) N° pts Age, years Treatm ent RR MS ( range) ( % ) Medical Research 339 67 (35–82) Oral etoposide 45 * 130 d* Council (96) 68 (45–83) IV Chemotherapy 51 183 d (EV or CAV) Souhami (97) 155 66 (50–86) Oral etoposide 33* 4.8 m* 67 (49–80) IV Chemotherapy 46 5.9 m (PE or CAV)

Yrs: years; RR: response rate; MS: median survival; IV: intravenous; EV: Etoposide and vincristine; CAV: Cyclophosphamide, doxorubicin, vincristine; PE: Cisplatin and etoposide; * : p< 0.05

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Auperin A et al. N Engl J Med 1999

Indirect and Subgroup Analyses

Characteristic Relative risk of death Relative risk of brain m etastases Age ( years) ( 9 5 % CI ) ( 9 5 % CI ) < 55 0.84 (0.65–1.02) 0.55 (0.39–0.77) 55–64 yr 0.90 (0.73–1.11) 0.49 (0.35–0.68) > 65 yr 0.79 (0.60–1.03) 0.37 (0.24–0.59)

First-line treatm ent: pancranial radiotherapy

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Lim ited disease SCLC in elderly patients

› Chem oradiation › Same benefit in elderly as in younger patients › Higher toxicity › The role of thoracic radiotherapy seem s less im portant in

• lder patients

› Single agent chem otherapy is active › Carboplatin com binations are feasible › Com bination chem otherapy results in higher responses and longer m edian survival than single agent › Prophylactic pancranial radiotherapy is effective in reducing brain m etastasis

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Sm all cell lung cancer: extensive disease

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First-line treatm ent: single agent

Author ( year) Age N°pts Treatm ent RR MST ( years) ( % ) ( m onths) Smit (89) > 70 22 Oral etoposide 63 9 Bork (97) > 70 30 Oral etoposidea 4.6 25 Oral etoposideb 7.2 Quoix (92) > 70 22 Epirubicin 45 Cerny (88) > 70 16 Teniposide 25 1.7 Tummarello (92) > 70 11 Teniposide 49 9 Cascinu (97) > 65 10 Teniposide 10 6

a: prolonged administration; b: every 3 weeks; MST = median survival time; NR = not reported; RR = response rate Rossi A et al. Oncologist 2005

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First-line treatm ent: com binations

Author ( year) Age N°pts Treatm ent RR MST ( years) ( % ) ( m onths) Gridelli (02) > 65 38 Carbo + vino + G-CSF 39.3 7.9 Westeel (89) > 65 41 PAVE 87 10.8

carbo: carboplatin; vino: vinorelbine; G-CSF: granulocyte colony stimulating factor; PAVE: cisplatin, doxorubicin; vincristine, etoposide; RR: response rate; MST = median survival time Rossi A et al. Oncologist 2005

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Slotman B et al. N Engl J Med 2007

Indirect and Subgroup Analyses

First-line treatm ent: pancranial radiotherapy

Irradiation (N = 143); median age (years) (range): 62 (37-75); control (N = 143); median age (years) (range): 63 (39–75)

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Extensive disease SCLC in elderly patients

› Single agent chem otherapy is active › Platinum com binations are feasible › Prophylactic pancranial radiotherapy is effective

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Treatm ent of lung cancer in the elderly

Geriatric frailty

• ADL dependency
• > 3 co-morbidities
• Geriatric syndrome

Life expectancy based on

• Age
• Co-morbidity

Life expectancy > cancer survival Life expectancy < cancer survival Contra-indications anti-cancer treatment Risk and benefits anti-cancer treatment IADL Nutritional status Social structure Risks < Benefits Risks > Benefits Anti-cancer treatment Follow up Palliative care Cancer influences QoL No influence of cancer on QoL

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