lung cancer in the elderly - siog · number of patients all-male lung cancer-male all-women lung...

Lung cancer in the elderly

D. Schrijvers, MD, PhDZiekenhuisnetwerk Antwerpen(ZNA)-Middelheim

AntwerpBelgium

1 30

Incidence and mortality of all cancers and lung cancer in relation to age and gender (US)

0

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)

Num

ber o

f pat

ient

s

All-male Lung cancer-male All-women Lung cancer-women

National Program of Cancer Registries (NPCR) 2004

0

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)

Num

ber o

f pat

ient

s

All-male Lung cancer-male All-women Lung cancer-women

Incidence Mortality

2 30

Early-stage non-small cell lung cancer

3 30

Surgery

Author (year) N° pts Stage Positive prognostic factors Outcome ~ 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 =

4 30

Radiotherapy

Treatment Overall survival (%)

No 6–14 (5-year)

Conventional RT 34 (3-year)

Stereotactic RT 70 (5-year)

Haasbeek CJ et al. Oncologist 2008

5 30

Adjuvant cisplatin-based chemotherapy

Trial ALPI ANITA BLT IALT JBR.10

N° patients 1.101* 840 307 1.867 482Eligibility

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

6 30

Adjuvant cisplatin-based chemotherapy: overall survival by treatment 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 > 70 years

7 30

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 chemotherapy› No survival benefit >70 years

8 30

Advanced non-small cell lung cancer

9 30

First-line treatment: comparison young-elderly

Author (year) Treatment RR(%) MOS (months) 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

10 30

First-line treatment in elderly patients: single agent

Author (year) Treatment N pts RR(%) MOS (wks) 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

11 30

First-line treatment in elderly patients: combinations


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 23RR: 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

12 30

First-line treatment in elderly patients: platinum compounds/targeted agents

Author (year) Treatment N pts RR(%) MOS (wks) 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

13 30

Second-line treatment in elderly patients


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

14 30

Advanced NSCLC in elderly patients

› First-line chemotherapy› 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 › Similar median overall survival or 1-year survival rates › Slightly more toxic

› Platinum combinations› Cisplatin more toxic than carboplatin

› Targeted agents› Bevacizumab more toxic

› Second-line chemotherapy› Targeted agents are treatment option

15 30

Small cell lung cancer: limited disease

16 30

First-line treatment

Author (year) Age N°pts Treatment MST 5YS p(years) (months) (%)

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

Rossi A et al. Oncologist 2005

17 30

First-line treatment: chemoradiation

Author (year) Age N°pts Treatment RR MST(years) (%) (months)

Murray (98) >70 55 CAV (1 cycle) + PE (1 cycle) 89 12.620–30 Gy

Jeremic (98) 72 72 cPE (2 cycles) 75 1545 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


18 30

First-line treatment: chemoradiation

› 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

19 30

First-line treatment: single agent


Smit (89) > 70 13 Oral etoposide 84 16Bork (97) > 70 32 Oral etoposide 7

30 Oral etoposide 7.5

Quoix (92) > 70 18 Epirubicin 50

Cerny (88) > 70 16 Teniposide 37.5 7.5Tummarello (92) > 70 13 Teniposide 61 10 Cascinu (97) > 65 12 Teniposide 30 8

MST = median survival time; NR = not reported; RR = response rate


20 30

First-line treatment: carboplatin combinations


Evans (95) > 65 11 carbo + etoa 88 12.2 Matsui (98) > 70 16 carbo + etoa 93 15.1Okamoto (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


21 30

First-line treatment: single agent versus combinations

Study (year) N° pts Age, years Treatment 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

22 30

Auperin A et al. N Engl J Med 1999

Indirect and Subgroup Analyses

Characteristic Relative risk of death Relative risk of brain metastases

Age (years) (95% CI) (95% 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 treatment: pancranial radiotherapy

23 30

Limited disease SCLC in elderly patients

› Chemoradiation › Same benefit in elderly as in younger patients › Higher toxicity

› The role of thoracic radiotherapy seems less important in older patients

› Single agent chemotherapy is active› Carboplatin combinations are feasible› Combination chemotherapy results in higher responses and

longer median survival than single agent› Prophylactic pancranial radiotherapy is effective in

reducing brain metastasis

24 30

Small cell lung cancer: extensive disease

25 30

First-line treatment: single agent


Smit (89) > 70 22 Oral etoposide 63 9Bork (97) > 70 30 Oral etoposidea 4.6

25 Oral etoposideb 7.2

Quoix (92) > 70 22 Epirubicin 45

Cerny (88) > 70 16 Teniposide 25 1.7Tummarello (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


26 30

First-line treatment: combinations


Gridelli (02) > 65 38 Carbo + vino +G-CSF 39.3 7.9Westeel (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


27 30

Slotman B et al. N Engl J Med 2007

Indirect and Subgroup AnalysesFirst-line treatment: pancranial radiotherapy

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

28 30

Extensive disease SCLC in elderly patients

› Single agent chemotherapy is active› Platinum combinations are feasible › Prophylactic pancranial radiotherapy is effective

29 30

Treatment 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 benefitsanti-cancer treatmentIADLNutritional statusSocial structure

Risks < Benefits Risks > Benefits

Anti-cancer treatment

Follow up Palliative care

Cancer influences QoLNo influence of cancer on QoL

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lung cancer in the elderly - siog · number of patients all-male lung cancer-male all-women lung...

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