1 / 53

Is there a role for chemotherapy in elderly patients? – YES

Pneumology. Istanbul, 7. 5. 2010. Is there a role for chemotherapy in elderly patients? – YES. Rudolf M. Huber. University of Munich. Age and gender distribution of lung cancer. Germany 2002.

kaori
Download Presentation

Is there a role for chemotherapy in elderly patients? – YES

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Pneumology Istanbul, 7. 5. 2010 Is there a role for chemotherapy in elderly patients? – YES Rudolf M. Huber University of Munich

  2. Age and gender distribution of lung cancer Germany 2002 GEKID Gesellschaft der epidemiologischen Krebsregister in Deutschland e. V. in Zusammenarbeit mit dem Robert Koch Institut. Krebs in Deutschland, Häufigkeiten und Trends. 5. überarbeitete, aktualisierte Ausgabe. Saarbrücken: GEKID, 2006 Huber

  3. Chemotherapy in Elderly Patients Quoix E: Chemotherapy in advanced NSCLC. In Spiro SG, Huber RM, Janes SM (eds.): Thoracic malignancies: EurRespir Mon, 2009, 44, 271–283. Huber Patients aged > 65 yrs represent about 50% of all patients with lung cancer and patients > 70 yrs about 30%. Elderly patients are under represented in clinical trials making any statement about the best treatment according to geriatric status very difficult

  4. What does “elderly” mean? Huber • Generally refers to a period of accelerated decline in physical functioning. • Definitions currently in use • Age > 70 years • Age> 65 years (East-Asian literature) • Elderly < 75 years • Very elderly > 75 years • The oldest old > 85 years

  5. Neurology CNS PNP Organ Systems Pneumology Cardio-vascular Age Gender BMI Infections Hematology Nephrology CrCl ultrasound Gastro- enterology Reduced drug metabolism and organ reserve Smoking and age cause damage to many organs Huber

  6. Chemotherapy in Elderly Patients • NSCLC – first-line • monotherapy • non-platinum doublets • platinum-based doublets • NSCLC – second-line • SCLC • Age vs. comorbidity

  7. Elderly* Lung Cancer Vinorelbine Italian Study Group (ELVIS) * > 70 yearsoldvinorelbine 30 mg/m2 d 1 and 8 J NatlCancerInst91 (1999) a6422 Huber

  8. BSC vs BSC plus vinorelbine for elderly advanced NSCLC: the ELVIS study BSC vs. vinorelbine Median survival: 21 wks vs. 28 wks; Survival at 6/12 months: 41/14% vs. 55/32% With vinorelbine significant improvement in QoL J Natl Cancer Inst. 1999; 91: 66–72 Huber

  9. Chemotherapy in Elderly NSCLC Patients • Gemcitabine is the second most studied drug in elderly patients with quite a number of phase II studies demonstrating its efficacy in this subpopulation of patients. Shepherd FA ea. Semin Oncol 1997; 24: Suppl. 7, S7-50–S7-55. Ricci S ea. Lung Cancer 2000; 27: 75–80. Quoix E ea. Lung Cancer 2005; 47: 405–412. Huber

  10. N=181 Elderly Patients withAdvanced NSCLC • Stratification: • Institution • Stage IV/IIIB • PS 0-1/2* Docetaxel vs. Vinorelbine in Elderly Patients (> 70 years old) median 76 years, range 70 – 86 y Docetaxel60 mg/m2 d 1, 22 Vinorelbine 25 mg/m2d 1, 8, 22, 29 Both treatments were repeatedover 4 cycles to disease progression *ECOG 0-1 98,9 vs 93,4% Kudoh et al. J Clin Oncol. 2006;24:3657-3663. Huber

  11. Docetaxel vs. Vinorelbine in Elderly Patients: Response and Survival Kudoh et al. J Clin Oncol. 2006;24:3657-3663. Huber

  12. Docetaxel vs. Vinorelbine in Elderly Patients (> 70 years old) Overall survival for patients treated with docetaxel (n = 89) or vinorelbine (n = 91) median progression-free survival (5.5 vs 3.1 months; P < .001) Kudoh, S. et al. J Clin Oncol; 24:3657-3663 2006 Huber

  13. Phase III Study of Docetaxel (n = 89)Compared With Vinorelbine (n = 91) in Elderly Patients With Advanced NSCLC Forest plot of odds ratio for global quality of life (QoL) and disease-related symptoms analyses b6502 Huber Kudoh S ea. J Clin Oncol; 24:3657-3663 2006

  14. Single-agent vs. Non-platinum based doublet FrasciG ea. J ClinOncol 2000; 18: 2529–2536 The South Italian Cooperative Oncology Group (SICOG) Phase III trial of vinorelbine (30 mg/m2; d 1 and 8, every 21 days) vs. vinorelbine/ gemcitabine doublet (vinorelbine: 30 mg/m2; gemcitabine 1200 mg/m2; both drugs on d 1 and 8, every 21 days) Huber

  15. Single-agent vs. Non-platinum based doublet Frasci G ea. J ClinOncol 2000; 18: 2529–2536 Frasci G ea. Lung Cancer 2001; 34 (4 Suppl): S65–S69. Huber • Prematurely terminated at interim analysis • Significant survival benefit for combination: • Median OS 29 wks vs 18 wks • Estimated 6-month and 1-year survival:56/30 compared with 32/13% (P < 0.01). • Multivariate Cox analysis, after adjustments:Risk of death in the combination arm 0.48 (95% CI 0.29 to 0.79; P < 0.01) • Symptoms and QoL deterioration more likely with monotherapy

  16. Chemotherapy in Elderly NSCLC PatientsMILES Gridelli C, Perrone F, Gallo C, et al. Chemotherapy for elderly patients with advanced non-small cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst 2003; 95: 362–372. The combination of vinorelbine and gemcitabine versus monotherapy with either of these two agents did not provide any benefit (n = 700 patients). Huber

  17. Vinorelbine, Gemcitabine or Vinorelbine+ Gemicitabine (MILES) Gridelli C ea. J Natl Cancer Inst 2003; 95: 362–372. Huber

  18. Gemcitabine with either paclitaxel or vinorelbine vspaclitaxel or gemcitabine alone for elderly or unfit advanced NSCLC Comella P ea. British Journal of Cancer (2004) 91, 489–497 Huber

  19. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced NSCLC Actuarial survival Comella P ea. British Journal of Cancer (2004) 91, 489–497 Huber

  20. Gemcitabine mono vs gemcitabine 3rd-generation doublet Russo A ea. Cancer 2009; 115: 1924–1931. Meta-analysis of a gemcitabine third-generation agent doublet versus single-agent treatment in elderly NSCLC patients Significantly higher overall response rate: combination vs. single agent; OR 0.65; P < 0.001 Trend toward higher survival in favor of combination treatment (OR 0.78; P = 0.169) Similar toxicity, except thrombocytopenia Huber

  21. Taiwan: cisplatin plus weekly paclitaxel or vinorelbine Median survival times 15 months in the younger patients (n=70) and 11.7 months in the elderly patients (n=70; p=0.598) Chen Y-M ea. CHEST 2005; 128:132–139 Huber

  22. NSCLC – platinum-based doublets Okamoto I ea. Jpn J ClinOncol 2005;35(4)188–194 Huber Twenty-five patients aged >70 years (median, 76; range, 70–83) with chemotherapy-naive advanced NSCLC were enrolled between January 2001 and July 2003. Patients received carboplatin at an AUC of 5 mg/ml/min and paclitaxel at 180 mg/m2 on the first day of consecutive 3 week periods.

  23. NSCLC – platinum-based doublets Treatment response and toxicity according to patient age Okamoto I ea. Jpn J ClinOncol 2005;35(4)188–194 Huber

  24. Chemotherapy in Elderly NSCLC Patients PujolJL ea. J ThoracOncol 2006; 1: 328–334. Huber Combined carboplatin and paclitaxel was found to be highly effective and safe in a phase II study. This approach is now being investigated in a randomised trial comparing single agent therapy (vinorelbine or gemcitabine) with carboplatin and paclitaxel (French Intergroup of Thoracic Oncology).

  25. Paclitaxelplus carboplatin versus single-agent paclitaxel Lilenbaum RC ea. J ClinOncol 2005; 23: 190–196. Huber • Subgroup analysis of a study comparing paclitaxelmonotherapy to paclitaxel/ carboplatin doublet • Elderly patients benefitted from the combination regimen median OS for monotherapyvs doublet:5.8 versus 8.0 months; P = nonsignificant • Lack of statistical significance likely due to the small numbers

  26. Single agent versus platinum-based doublet (JCOG0207) Tsukada H ea. Proc Am Soc Clin Oncol 2007; 25: (Abstr 7629) Randomized controlled trial comparing docetaxel (D)-cisplatin (P) combination with D alone in elderly with advanced NSCLC Pts ≥70 years old received either D/ P(D 20 mg/m2, P 25 mg/m2, d 1, 8, 15) or D (25 mg/m2, on the same schedule). Prematurely closed after only 63 patients per arm (interim analysis showed possible benefit with doublet in the 70–74 year subgroup). Huber

  27. Gemcitabine plus carboplatin versus single-agent gemcitabine Sederholm C ea. J ClinOncol 2005; 23: 8380–8388. A preplanned subgroup analysis of elderly patients (n = 121): both young and elderly patients showed benefit in OS when treated with the combination regimen. Elderly patients experienced more hematological toxicity when compared with younger patients. Huber

  28. Comparison of platinum-doublets Gridelli C ea. J ClinOncol 2007; 25: 4663–4669. • Two doublets were evaluated in 159 elderly (aged ≥ 70 years) NSCLC patients: • cisplatin/gemcitabine • cisplatin/ vinorelbine • Both doublets were shown to be feasible and active in elderly patients. Huber

  29. NSCLC – platinum-based doublets Pallis AG ea. Ann Oncol 21: 692–706, 2010 No elderly-specific platinum-based prospective phase III trials have been conducted Retrospective age-specific subgroup analyses of several phase III trials indicate outcome measures, namely response rate, PFS and OS, do not differ significantly between age groups Regarding severe toxicity (grade ≥ 3), some studies report a higher incidence in elderly patients, while others do not Huber

  30. NSCLC – second-line Weiss GJ ea. J ClinOncol 2006; 24: 4405–4411 Age-specific subgroup analysis of a randomized phase III trial comparing pemetrexed with docetaxel in pretreated patients with NSCLC. The original trial randomized 571 patients. Eighty-six of those (15%) were ≥70 years old. Huber

  31. NSCLC – second-line Weiss GJ ea. J ClinOncol 2006; 24: 4405–4411 Objective response rates, median PFS and OS were not significantly different between younger and elderly patients. Elderly pts had a median OS of 9.5/7.7 months for pemetrexed / docetaxel arms In younger pts the OS was 7.8/8.0 months for pemetrexed/docetaxel arms No significant difference between younger and elderly patients regarding toxicity Huber

  32. Efficacy and safety of pemetrexed in elderly cancer patients Kulkarni PM ea. CritRevOncol/Hematol (2008) Huber

  33. Efficacy and safety of pemetrexed in elderly cancer patients Non-haematological toxicities: no significant differences Kulkarni PM ea. Crit Rev Oncol/Hematol (2008) Huber

  34. Erlotinib second-line in elderly Wheatley-Price P ea. J Clin Oncol 2008; 26: 2350–2357. Subgroup analysis of BR.21 study 163 (22% of the original cohort; 112 on erlotinib, 51 on placebo), pts ≥70 years old Nosignificant difference between young and elderly pts in RR, PFS and OS (erlotinib: 6.4/ 7.6 mo.; P = 0.85) Elderly patients experienced significantly more ≥ grade 3 toxic effects (35% vs. 18% for elderly vs. young patients; P < 0.001) Huber

  35. NSCLC – second-line Di Maio M ea. Eur J Cancer (2009), doi:10.1016/j.ejca.2009.12.013 Individual data from nine randomised trials of 2nd-line treatment in advanced NSCLC were analysed. Primary end-point was overall survival. 1197 pts (97%) had complete data sets. Prognosis of pts eligible for 2nd-line treatment of advanced NSCLC is significantly dependent on gender, PS, histology, stage, previous use of platinum and response to first-line. Huber

  36. 2009 ASCO Recommendations • Recommendation A4. The evidence does not support the selection of a specific first-line chemotherapy drug or combination based on age alone. • Recommendation B2. The evidence does not support the selection of a specific second-line chemotherapy drug or combination based on age alone. Huber

  37. NCCN Practice Guidelines NCCN Practice Guidelines 2008 Advanced NSCLC: Fit elderly merit appropriate treatment Single agent therapy or platinum-based combinations are a reasonable alternative in PS 2 patients or the elderly Unfit of any age (performance status 3 – 4) do not benefit from cytotoxic treatment Huber

  38. Chemotherapy in Elderly NSCLC Patients • In patients with stage IV NSCLC who are elderly (> 70 to 79 years) single-agent chemotherapy is recommended for most patients. Grade of recommendation, 1A • However, in patients with stage IV NSCLC who are elderly (> 70 to 79 years) and have a good PS and lack significant comorbidities, two-drug combination chemotherapy is recommended as an option. Grade 1B • In patients with stage IV NSCLC who are > 80 years old, the benefit of chemotherapy is unclear and should be decided on based on individual circumstances. Grade 2C ACCP 2007 Huber

  39. NSCLC elderly patients – recommendations German Society ofPneumology. Pneumologie 2010; 64, Supplement 2: e1– e164 Huber Older age should not exclude patients from a treatment modality (chemotherapy, radiotherapy, surgery). Comorbidity is more relevant (Level C).

  40. SCLC Owonikoko TK ea. JNCCN 2008;6:333–344 Huber Approximately 40% of SCLC cases are diagnosed in patients older than 70 years, and this proportion continues to rise in contrast to the continued decline in incidence of SCLC among the general population. In the United States 10% are diagnosed in patients older than 80 years.

  41. SCLC – extensive disease Gridelli C ea. J ClinOncol 25 (2007):1898-1907 Prospective trials have specifically addressed elderly patients with SCLC, and carboplatin plus etoposide is the most investigated regimen (Quoix E 2001, Larive S 2002) The same chemotherapy as used in younger patients induces reasonable activity, albeit with increased toxicity, in the elderly. Huber

  42. SCLC – extensive disease (etoposide phosphate and carboplatin) Main issues according to age Quoix E ea. Ann Oncol 12:957-962, 2001 Huber

  43. USA: Chemotherapy and Survival Benefit in Elderly (> 65 yrs) With Advanced NSCLC First-line: Distribution by type of chemotherapy Source: Surveillance, Epidemiology and End Results–Medicare, 1997-2002. Davidoff AJ ea. J Clin Oncol; 28:2191-2197 2010 Huber

  44. Adjusted survival benefit of chemo-therapy for elderly advanced NSCLC Chemo vs BSC: A: Proportional hazards; B: nonproportional hazards Platinum-doublet vs single-agent: C: proportional hazards Source: Surveillance, Epidemiology and End Results–Medicare, 1997-2002. Davidoff AJ ea. J ClinOncol; 28:2191-2197 2010 Huber

  45. Effect of comorbidity on treatment and prognosis of elderly with NSCLC Janssen-Heijnen MLG ea. Thorax 2004;59:602–607 All patients with NSCLC diagnosed between 1995 and 1999 in the southern part of the Netherlands (n = 4072) were included In patients with non-localised NSCLC the proportion receiving chemotherapy was considerably higher for those aged less than 60 years (24%) than in those aged 80 or older (2%). Huber

  46. Treatment of non-localised NSCLC according to age, and comorbidity Janssen-Heijnen MLG ea. Thorax 2004;59:602–607 Huber

  47. Adverse Events Among the Elderly Receiving Chemotherapy for Advanced NSCLC Chrischilles EA ea. J Clin Oncol; 28:620-627 2010 • Of 1,371 patients, 58% received chemotherapy and 35% had AEs. • Age < 55 years: 72% received chemotherapy • Age > 75 years: 47% received chemotherapy • Platinum-based therapies were less common in the older-age groups. Huber

  48. Adverse Events Among the Elderly Receiving Chemotherapy for Advanced NSCLC* *Cancer Care Outcomes Research and Surveillance Consortium Chrischilles EA ea. J Clin Oncol; 28:620-627 2010 • Pretreatment medical event rates: • 18.6% for pts < 55 yrs • 9.2% for pts ≥ 75 yrs (adjusted rate ratio 0.49) • Older pts were more likely to have AEs during chemotherapy. • Adjusted rate ratios compared with < 55 yrs • 1.70 for 65- to 74-yr-olds • 1.34 for those ≥75 yrs Huber

  49. Age and Comorbidity As Independent Prognostic Factors in NSCLC Therapy Asmis TR ea. J ClinOncol 26 (2008):54-59. Two large, prospectively randomized Canadian trials of systemic chemotherapy (adjuvant/palliative setting) for NSCLC. 1,255 patients were included The median age was 61 yrs (range: 34 - 89 yrs); 34% of patients were elderly (>= 65 yrs) 31% had comorbid conditions. Huber

  50. Age and Comorbidity As Independent Prognostic Factors in NSCLC Therapy Asmis TR ea. J ClinOncol 26 (2008):54-59. Although age did not influence overall survival, the CCIS appeared prognostic (CCIS 1 v 0; hazard ratio 1.28; 95%CI, 1.09 to 1.5; P=.003). In these large, randomized trials, the presence of comorbid conditions (CCIS ≥ 1), rather than age more than 65 years, was associated with poorer survival. Huber

More Related