elderly patients with advanced nsclc: emerging role of targeted therapy

Elderly Patients with Advanced NSCLC:Elderly Patients with Advanced NSCLC: Emerging Role of Targeted Therapy Emerging Role of Targeted Therapy

Corey J Langer MD, FACPCorey J Langer MD, FACPProfessor of MedicineProfessor of Medicine

Director of Thoracic OncologyDirector of Thoracic OncologyUniversity of Pennsylvania,University of Pennsylvania,

Philadelphia, PAPhiladelphia, [email protected]

Demographics of Lung Cancer in Demographics of Lung Cancer in the Older Patientthe Older Patient

Individuals > age 65: fastest growing segment of U.S. populationIndividuals > age 65: fastest growing segment of U.S. populationMore than 2/3 of patients with adv. lung cancer older than 65More than 2/3 of patients with adv. lung cancer older than 65**

Median age of diagnosis for lung cancer in the U.S. is 70Median age of diagnosis for lung cancer in the U.S. is 70**

35% of lung cancer patients 35% of lung cancer patients >> 75 75**

Likelihood of receiving treatment decreases with advancing ageLikelihood of receiving treatment decreases with advancing ageClinical trial participation also decreases with advancing ageClinical trial participation also decreases with advancing age– Analysis of SWOG trials 1993 – 1996 (Hutchins NEJM 341:2061,1999)Analysis of SWOG trials 1993 – 1996 (Hutchins NEJM 341:2061,1999)

39% of patients on lung trials > 65 vs. 66% of general population > 6539% of patients on lung trials > 65 vs. 66% of general population > 65– NCI analysis 1997 – 2000 (Lewis J Clin Oncol 21:1383, 2003)NCI analysis 1997 – 2000 (Lewis J Clin Oncol 21:1383, 2003)

42% of patients on lung trials > 65 vs. 70% of general population > 6542% of patients on lung trials > 65 vs. 70% of general population > 65

*SEER Data 2000 - 2003

Elderly Patients - Representation Elderly Patients - Representation in Clinical Trialsin Clinical Trials

65% of lung cancer patients are 65% of lung cancer patients are 65 6550% of lung cancer patients are 50% of lung cancer patients are 7070Elderly representation on US NSCLC TrialsElderly representation on US NSCLC Trials

StudyStudy % % 7070E5592E5592 15% 15%S9509/9305S9509/9305 19% 19%E1594E1594 20% 20%E4599E4599 26% 26%

CALGB 9730CALGB 9730 27% 27%

Chemotherapy in the Elderly Patient: Chemotherapy in the Elderly Patient:

Special ChallengesSpecial Challenges

Higher frequency of comorbid conditionsHigher frequency of comorbid conditions

Higher prevalence of polypharmacy increasing the risk of Higher prevalence of polypharmacy increasing the risk of adverse drug interactionsadverse drug interactions

Reduced hepatic, renal, lung function, immune Reduced hepatic, renal, lung function, immune competence and bone marrow reservecompetence and bone marrow reserve

Impaired social, emotional or financial resourcesImpaired social, emotional or financial resources

Prospective Phase III Chemotherapy Prospective Phase III Chemotherapy Trials in Elderly Patients with Trials in Elderly Patients with

Advanced NSCLCAdvanced NSCLC ELVIS (1999) (154 pts)ELVIS (1999) (154 pts)– vinorelbine vs. BSC: vinorelbine vs. BSC: improved survival and QOL with vinorelbineimproved survival and QOL with vinorelbine

SIOG (2000) (120 pts)SIOG (2000) (120 pts)– vinorelbine vs. vinorelbine + gemcitabine: vinorelbine vs. vinorelbine + gemcitabine: improved survival, but improved survival, but

enhanced toxicity with the combinationenhanced toxicity with the combination

MILES (2003) (698 pts)MILES (2003) (698 pts)– vinorelbine vs. gemcitabine vs. vinorelbine + gemcitabine: vinorelbine vs. gemcitabine vs. vinorelbine + gemcitabine:

overall survival similar among arms; combination regimen more overall survival similar among arms; combination regimen more toxictoxic

WJTOG (2006) (182 pts)WJTOG (2006) (182 pts)– vinorelbine vs. docetaxel: vinorelbine vs. docetaxel: improved response, PFS and survival improved response, PFS and survival

with docetaxel (though underpowered to show a statistically with docetaxel (though underpowered to show a statistically significant benefit wrt OS)significant benefit wrt OS)

Single Agent Chemotherapy in Elderly Patients with Advanced NSCLC

*Gridelli, J Natl Cancer Inst 1999; 85:365-376.‡Frasci et al, JCO 2000; 18(13): 2529-2536 Gridelli, J Natl Cancer Inst 2003; 95: No5

* p<0.05

Author Regimen N Response MS (mo) 1 YR Vinorelbine 78 20% 6.5 32%*

BSC 76 -- 4.9 14%

Gemcitabine + Vinorelbine 76 22% 7 30%*

Vinorelbine 76 15% 4.5 13%

Vinorelbine 233 18.4% 8.8 41% Gemcitabine 233 17.3% 6.6 26% Gemcitabine + Vinorelbine 237 20% 7.6 31%

Gridelli*

Frasci‡

Gridelli

TREATMENT SCHEMA – WJTOG TREATMENT SCHEMA – WJTOG 20052005

StratificationInstitutionStage IV/IIIBPS 0-1/2

StratificationInstitutionStage IV/IIIBPS 0-1/2

RANDOMIZE

RANDOMIZE

Docetaxel (D)Docetaxel (D)

Docetaxel60 mg/m2

Day 1 8 15 22 29

Day 1 8 15 22 29

Vinorelbine (V)Vinorelbine (V)

Vinorelbine25 mg/m2

Both treatments were repeated over 4 cycles to disease progression.

Takeda ASCO 2005, A-7009

Docetaxel vs Vinorelbine for Elderly Docetaxel vs Vinorelbine for Elderly Patients with Advanced NSCLCPatients with Advanced NSCLC

182 pts accrued182 pts accrued

Toxicities consistent with known profile of each agentToxicities consistent with known profile of each agent

Global QoL similar but overall symptom improvement Global QoL similar but overall symptom improvement better with D than V better with D than V

Higher ORR with D (23% vs. 10%; p=0.019)Higher ORR with D (23% vs. 10%; p=0.019)

Longer PFS with D (5.4 vs. 3.1 mo; p<0.001)Longer PFS with D (5.4 vs. 3.1 mo; p<0.001)

Survival:Survival: MST MST 1-y Surv1-y Surv– D D 14.3mo14.3mo 59% 59%

– V V 9.9 mo 37% 9.9 mo 37% HR=0.780 (0.561-1.085) p=0.138

WJTOG – ASCO 2005

Retrospective Analyses of Platinum-Retrospective Analyses of Platinum-based Doublets in Elderly (based Doublets in Elderly (>> 70) Patients 70) Patients

with Advanced NSCLCwith Advanced NSCLCSeveral subset analyses conducted assessing outcome in Several subset analyses conducted assessing outcome in patients patients >> age 70 age 70– SWOG 9509/9308 - carbo/paclitaxel vs. cis/vinorelbine (Kelly 2001)SWOG 9509/9308 - carbo/paclitaxel vs. cis/vinorelbine (Kelly 2001)– ECOG 5592 – carbo/etoposide vs. carbo/paclitaxel (Langer 2002)ECOG 5592 – carbo/etoposide vs. carbo/paclitaxel (Langer 2002)– CALGB 9730 – carbo/paclitaxel (Lilenbaum 2002)CALGB 9730 – carbo/paclitaxel (Lilenbaum 2002)– ECOG 1594 – four platinum doublets (Langer 2003)ECOG 1594 – four platinum doublets (Langer 2003)– TAX 326 – cis/docetaxel vs. cis/vinorebine vs. carbo/docetaxel TAX 326 – cis/docetaxel vs. cis/vinorebine vs. carbo/docetaxel

(Fossella 2003)(Fossella 2003)

No differences in survivalNo differences in survivalTrend for greater toxicity in some studies, particularly Trend for greater toxicity in some studies, particularly myelosuppressionmyelosuppressionTrend for improved tolerance of carboplatin vs. cisplatinTrend for improved tolerance of carboplatin vs. cisplatinMajor potential limitation – these elderly subsets may not be Major potential limitation – these elderly subsets may not be representative of the general elderly populationrepresentative of the general elderly population

JCOG phase III randomized trial in JCOG phase III randomized trial in advanced NSCLC elderly patientsadvanced NSCLC elderly patients

Age > 70 yrsIIIB-IV NSCLC PS 0- 1

Randomization

Weekly Docetaxel

Weekly CDDP+ Docetaxel

DOC 25 mg/m2

day 1, 8, 15every 4 weeks

CDDP 25 mg/m2

DOC 20 mg/m2

day 1, 8, 15every 4 weeksTsukada et al, ASCO ’07, A-7629

Phase II Trial of Cisplatin Phase II Trial of Cisplatin + Docetaxel in the Elderly+ Docetaxel in the Elderly

Results:Results:N= 33N= 33Median age: 77Median age: 77Median cycles: 3 Median cycles: 3 ORR: 52%ORR: 52%MS: 15.8 mosMS: 15.8 mos1 YR OS: 64%1 YR OS: 64%2 YR OS: 26%2 YR OS: 26%

Ohe Y et al: Ann Onc 15:45-50, 2004

Schema:Schema:CDDP 25 mg/m2CDDP 25 mg/m2DOC 20 mg/m2DOC 20 mg/m2Days 1, 8, 15Days 1, 8, 15Q 4 wksQ 4 wks

JCOG phase III randomized trial in JCOG phase III randomized trial in advanced NSCLC elderly patientsadvanced NSCLC elderly patientsPremature TerminationPremature Termination

Trial aborted after DSMC determined that the 70-74 Trial aborted after DSMC determined that the 70-74 age group benefitted from DP over Dage group benefitted from DP over D

ArmArm DocDoc Doc-DDPDoc-DDP

NoNo 6363 6363

PFS (mo)PFS (mo) 3.73.7 6.26.2

MS (mo)MS (mo) 10.710.7 1717

1-yr OS (%)1-yr OS (%) 45.245.2 66.666.6

Gr 3-4 ANCGr 3-4 ANC 4.94.9 13.113.1

Gr 3-4 HGBGr 3-4 HGB 1.61.6 16.416.4

Gr 3-4 AnorexiaGr 3-4 Anorexia 8.38.3 24.224.2

TRDTRD 00 11

Tsukada et al, ASCO ’07, A-7629

Molecularly Targeted Agents: Role in Elderly Molecularly Targeted Agents: Role in Elderly Patients with Advanced NSCLCPatients with Advanced NSCLC

Potential for increased use given “favorable” toxicity profilePotential for increased use given “favorable” toxicity profile

Limited prospective data to dateLimited prospective data to date

Retrospective analysis of BR21 showed that age did not dilute the survival benefit Retrospective analysis of BR21 showed that age did not dilute the survival benefit of erlotinib vs placebo in the 2of erlotinib vs placebo in the 2ndnd and 3 and 3rdrd line setting line setting

Prospective phase II trial with erlotinib suggests benefitProspective phase II trial with erlotinib suggests benefit

Subset analyses of extended access trials with single-agent gefitinib have Subset analyses of extended access trials with single-agent gefitinib have demonstrated clinical activity and modest toxicitydemonstrated clinical activity and modest toxicity

Phase II trial of gefitinib + gemcitabine or vinorelbine (Scagliotti ASCO 2004); Phase II trial of gefitinib + gemcitabine or vinorelbine (Scagliotti ASCO 2004); antineoplastic activity not enhanced; excessive toxicity for vinorelbine and gefitinibantineoplastic activity not enhanced; excessive toxicity for vinorelbine and gefitinib

Prospective phase III trial of gefitinib vs vinorelbine shows equivalent survival, Prospective phase III trial of gefitinib vs vinorelbine shows equivalent survival, improved QoL (IASLC ’07)improved QoL (IASLC ’07)

Retrospective analysis of bevacizumab combined with chemotherapy suggests Retrospective analysis of bevacizumab combined with chemotherapy suggests cautioncaution

BR.21: overall survivalBR.21: overall survival

Shepherd F, et al. N Engl J Med 2005.

HR=0.70 (0.58–0.85) Stratified log-rank p<0.001

100

80

60

40

20

0

Per

cent

age

0 6 12 18 24 30

ErlotinibPlacebo

At riskErlotinib 488 255 145 23 4

0 Placebo 243 107 50 9 0

0

Time (months)

Forest plot of survival by subsetsForest plot of survival by subsets

erlotinib:placeboPS 0–1PS 2–3

MaleFemale

<65 years65 years

AdenocarcinomaSquamous-cell carcinoma

Other histologyPrior weight loss <5%

Prior weight loss 5–10%Prior weight loss >10%

Never-smokerCurrent/ex-smoker

1 prior regimen2+ prior regimens

0 1 2 3 4

HR

Erlotinib for advanced non-small-cell lung cancer in Erlotinib for advanced non-small-cell lung cancer in the elderly: an analysis of the National Cancer Institute the elderly: an analysis of the National Cancer Institute

of Canada Clinical Trials Group Study BR.21of Canada Clinical Trials Group Study BR.21No significant demographic differences between age groups randomly assigned to erlotinib or placebo No significant demographic differences between age groups randomly assigned to erlotinib or placebo

Response rates were similar between age groups. Response rates were similar between age groups.

Elderly patients, compared with young patients, had significantly more overall and severe (grade 3 and Elderly patients, compared with young patients, had significantly more overall and severe (grade 3 and 4) toxicity (35% v 18%; P < .001), were more likely to discontinue treatment as a result of treatment-4) toxicity (35% v 18%; P < .001), were more likely to discontinue treatment as a result of treatment-related toxicity (12% v 3%; P < .0001), and had lower relative dose-intensity (64% v 82% received > related toxicity (12% v 3%; P < .0001), and had lower relative dose-intensity (64% v 82% received > 90% planned dose; P < .001). 90% planned dose; P < .001).

Conclusion: Elderly pts treated with erlotinib have similar survival and QOL benefits compared to Conclusion: Elderly pts treated with erlotinib have similar survival and QOL benefits compared to younger pts, with somewhat greater toxicityyounger pts, with somewhat greater toxicity

J Wheatley-Price P, Ding K, Seymour L, Clark GM, Shepherd FA JCO 2008 May 10;26(14):2350-7.

Elderly No PFS OS

Erlotinib 112 3.0 7.6

Placebo 51 2.1 5.0

P value 0.009 0.67

HR (95% CI) 0.63 (0.44-0.90) 0.92 (0.64-1.34)

Younger No PFS OS

Erlotinib 376 2.1 6.4

Placebo 192 1.8 4.7

P value < 0.0001 0.014

HR (95% CI) 0.64 (0.53-0.76) 0.73 (0.61-0.89)

Phase II Study of Erlotinib in Elderly Patients Phase II Study of Erlotinib in Elderly Patients with Previously Untreated Advanced NSCLC. with Previously Untreated Advanced NSCLC.

PIs: PIs: Janne, Jackman & Johnson MDJanne, Jackman & Johnson MDLocation:Location: Dana Farber and MGH Dana Farber and MGHRegimenRegimen: single agent 150 mg/d in chemo-naïve, PS 0-2 pts: single agent 150 mg/d in chemo-naïve, PS 0-2 pts

≥ ≥70yrs until PD or toxicity70yrs until PD or toxicityNN = 80; median age 76 (70-91); 63% Adenoca or BAC; 95% = 80; median age 76 (70-91); 63% Adenoca or BAC; 95%

never/former smokersnever/former smokersToxicities: Toxicities: gr gr >> 1 1 rash 79%; grade 3 rash (5); diarrhea 69%;rash 79%; grade 3 rash (5); diarrhea 69%;

9 pts D/C for toxicity; ILD (4), 1 fatality 9 pts D/C for toxicity; ILD (4), 1 fatality OR%:OR%: 10% -- of 8 responders, 5 female, 2 never and 6 10% -- of 8 responders, 5 female, 2 never and 6 former smokers; all had rashformer smokers; all had rashDC%:DC%: 51%; TTP: 3.5 mos 51%; TTP: 3.5 mosMedian Survival:Median Survival: 10.9 mos (95% CI 7.8 – 14.6 mo) 10.9 mos (95% CI 7.8 – 14.6 mo)1yr OS: 1yr OS: 46%: 46%: 2yr OS: 2yr OS: 19%19%EGFr Mutations:EGFr Mutations: (+) in 9/43 tested, corelated with RR, DC, TTP and OS (+) in 9/43 tested, corelated with RR, DC, TTP and OS

Jackman D ASCO-2005, A-7148, JCO ‘07

Conclusions: SA Erlotinib in Conclusions: SA Erlotinib in Elderly NSCLC Elderly NSCLC

Single agent activity and survival in Tx-Single agent activity and survival in Tx-naïve pts matches that observed with naïve pts matches that observed with conventional cytotoxicsconventional cytotoxics

Untoward toxicity not observed; no Untoward toxicity not observed; no unusual safety concernsunusual safety concerns

Jackman D ASCO-2005, A-7148, JCO ‘07

Gefitinib in Elderly NSCLC Gefitinib in Elderly NSCLC (Japanese experience)(Japanese experience)

Retrospective comparison comparing toxicity, response and survival Retrospective comparison comparing toxicity, response and survival outcomes for gefitinib in patients aged 75 years or older (elderly group) with outcomes for gefitinib in patients aged 75 years or older (elderly group) with patients aged younger than 75 years. patients aged younger than 75 years.

350 patients were eligible for this analysis, 350 patients were eligible for this analysis,

Multivariate analysis revealed elderly patients with lower Brinkman index Multivariate analysis revealed elderly patients with lower Brinkman index tended to be more sensitive to gefitinib (odds ratio: 4.57, 95% confidence tended to be more sensitive to gefitinib (odds ratio: 4.57, 95% confidence interval: 0.91-22.72, p = 0.0642). interval: 0.91-22.72, p = 0.0642).

Conclusions: Tx with gefitinib appeared to be as safe and effective in Conclusions: Tx with gefitinib appeared to be as safe and effective in elderly patients (aged 75 or older) with NSCLC as in non-elderly patientselderly patients (aged 75 or older) with NSCLC as in non-elderly patients

Hotta K, Ueoka H, Kiura K, Tabata M, Ogino A, Umenura S, Harita S, Gemba K, Yonei T, Bessho A, Maeda T, Tanimoto M

Acta Oncol. 2005;44(7):717-22 (Okayamo)

Age Cohort

No Gr 3-4 AEs

OR% MST

Elderly 92 9% 17 7.6m

Young 258 9% 21 9.3m

Gefitinib in the Elderly with NSCLCGefitinib in the Elderly with NSCLCProspective study of gefitinib 250 mg/d in advanced chemo-exposed NSCLC pts Prospective study of gefitinib 250 mg/d in advanced chemo-exposed NSCLC pts >> 70. 70. From August 2001 to May 2003, From August 2001 to May 2003,

40 consecutive pts enrolled from three Italian institutions from 8/01 to 5/03 40 consecutive pts enrolled from three Italian institutions from 8/01 to 5/03

OR% - 5% (1 CR, 1 PR) 18 disease stabilizations (NC: 45%) lasting at least 2 mos OR% - 5% (1 CR, 1 PR) 18 disease stabilizations (NC: 45%) lasting at least 2 mos

– six patients (15%) who had disease stabilisation of 6 months or longer, six patients (15%) who had disease stabilisation of 6 months or longer,

– median duration of response was 4.4 months (range 1.7-9.2). median duration of response was 4.4 months (range 1.7-9.2).

No data on PFS or OSNo data on PFS or OSSide effects generally mild and consisted of diarrhoea and skin toxicity.Side effects generally mild and consisted of diarrhoea and skin toxicity.

– Grade 1-2 diarrhoea in 23.6%; one pt experienced grade 4 diarrhoea, requiring Grade 1-2 diarrhoea in 23.6%; one pt experienced grade 4 diarrhoea, requiring hospitalization. hospitalization.

– Grade 1-2 skin toxicity, including rash, pruritus, dry skin, and acne in 20 pts (50%). Grade 1-2 skin toxicity, including rash, pruritus, dry skin, and acne in 20 pts (50%).

Conclusions: Gefitinib is safe and well tolerated in elderly pretreated NSCLC patients with Conclusions: Gefitinib is safe and well tolerated in elderly pretreated NSCLC patients with reasonable disease control rate.reasonable disease control rate.

Cappuzzo F, Bartolini S, Ceresili GL, Tamberi S, Spreafico A, Lombardo L, Gergorc V, Toschi L, Calandri C, Villa E, Crino L Br J Cancer. 2004 Jan 12;90(1):82-6

INVITE trial in advanced NSCLC elderly (>70 yrs) pts with PS < 2

Vinorelbine 30 mg/m2 days 1 + 8

Gefitinib(250 mg/d)

Prim. Obj.= time to progression

Crino et al IASLC ’07 Crino L, Cappuzzo F, Zatloukal R et al J Clin Oncol. 2008 Sep 10;26(26):4253-60

RP2RP2

INVITE trial in advanced NSCLC elderly (>70 yrs) pts with PS < 2

ArmArm NoNo PS 2PS 2 DCRDCR TOITOI PSIPSI Gr 3-5 Gr 3-5 ANCANC RashRash

VNRVNR 9999 16%16% 5454 1111 3131 42%42% 44%44% 4%4%

GEFGEF 9797 24%24% 4343 2323 3636 13%13% 0%0% 34%34%

HR for Gef vs VnrPFS: 1.19 (0.85, 1.69)OS: 0.98 (0.66, 1.47)

HR for Vnr vs Gef for 54 FISH (+)PFS: 3.13 (1.45, 6.73)OS: 2.88 (1.21, 6.83)

Crino et al IASLC ’07 Crino L, Cappuzzo F, Zatloukal R et al J Clin Oncol. 2008 Sep 10;26(26):4253-60

Conclusions: • Gefitinib and vinorelbine similar efficacy• Gefitinib better tolerated• Paradoxical benefit for VNR in FISH (+) pts

*PSI – Pulmonary symptom improvement

Phase II randomized trial of IRESSA + Phase II randomized trial of IRESSA + GEM or VNR in elderly NSCLC ptsGEM or VNR in elderly NSCLC pts

GEM+Gefitinib

GEM 1200 mg/m2, i.v., d 1-8, q21 IRESSA 250 mg/die, p.o., until to

PD

VNR+Gefitinib

VNR 30 mg/ m2, i.v., d 1-8, q21 IRESSA 250 mg/die p.o., until to

PD

Study Coordinators: C. Gridelli – G.V. Scagliotti

Accrual completed

RR

Randomized Phase II of Gefitinib in Randomized Phase II of Gefitinib in Combination with Vinorelbine or Combination with Vinorelbine or

Gemcitabine in Elderly Pts with NSCLCGemcitabine in Elderly Pts with NSCLCGr 3-4 ADRs in 87.5% in the 1Gr 3-4 ADRs in 87.5% in the 1stst 24 pts on VG 24 pts on VG– Including 72% gr 3-4 neutropenia Including 72% gr 3-4 neutropenia – 3 deaths which may have been Tx-related (1 septic 3 deaths which may have been Tx-related (1 septic

shock and cerebral infarct)shock and cerebral infarct)

ResultsResults VGVG GGGGNoNo 2424 3535CR/PRCR/PR 1/31/3 3 3TTP (d)TTP (d) 9191 9494MS (d)MS (d) 371371 275275

Phase 2 trial of docetaxel and gefitinib in Tx-Phase 2 trial of docetaxel and gefitinib in Tx-naïve pts with advanced NSCLC naïve pts with advanced NSCLC >> 70 yrs of age 70 yrs of age

Eligibility: Eligibility: chemotherapy-naïve NSCLC patients, 70 years of age or olderchemotherapy-naïve NSCLC patients, 70 years of age or older

Tx Design:Tx Design:– Docetaxel 75 mg/m(2) every 3 weeks - 2 cycles beyond maximal responseDocetaxel 75 mg/m(2) every 3 weeks - 2 cycles beyond maximal response– Gefitinib 250 mg po until PDGefitinib 250 mg po until PD

Primary endpoint - response rate (RR); Secondary endpoints : OS and PFS Primary endpoint - response rate (RR); Secondary endpoints : OS and PFS

RESULTS: RESULTS: 44 patients initiated therapy between March 2003 and May 2005. 44 patients initiated therapy between March 2003 and May 2005.

Seventeen patients (40%; 95% confidence interval [CI], 26%-57%) had a partial response Seventeen patients (40%; 95% confidence interval [CI], 26%-57%) had a partial response

48% had stable disease. 48% had stable disease.

Median PFS was 6.9 months (95% CI, 3.95-7.8 months). Median PFS was 6.9 months (95% CI, 3.95-7.8 months).

Median survival time was 9.6 months (95% CI, 4.6-16.3 months). Median survival time was 9.6 months (95% CI, 4.6-16.3 months).

Univariate analyses: sex; ECOG PS, and Charlson comorbidities index (CCI) score proved predictors of Univariate analyses: sex; ECOG PS, and Charlson comorbidities index (CCI) score proved predictors of improved survivalimproved survival

Multivariate analyses: female sex was a statistically significant predictor of survival. Multivariate analyses: female sex was a statistically significant predictor of survival. – median survivals were 22.8 months in women and 4.8 months in men. median survivals were 22.8 months in women and 4.8 months in men.

Most common adverse events being hyperglycemia, fatigue. Most common adverse events being hyperglycemia, fatigue.

CONCLUSIONSCONCLUSIONS: Combination docetaxel and gefitinib: active and well tolerated in patients with advanced : Combination docetaxel and gefitinib: active and well tolerated in patients with advanced NSCLC who are 70 years of age and older; merits further investigation especially in womenNSCLC who are 70 years of age and older; merits further investigation especially in women

Simon et al Cancer. 2008 May 1;112(9):2021-9.

Randomised phase II trial in NSCLC pts unsuitable for Plat-based CT (Elderly or PS 2)

Cetuximab + Gemcitabine X 6

cycles

Gemcitabine Cetuximab at PD

Gridelli C, Mencoboni M, Carrozza F et al. C225 and Gemcitabine in elderly or adult PS 2 advanced NSCLC pts : the CALC-1 randomized phase II trials. JCO 2008: 2(15S): 452s (A8117)

RR

ResultsResults

Arm PFS (mo) MS 1 yr OS

G + C 3 6 41%

G C* 4 9 31%

Elderly (n=58)

PS 2 (n=42)

Arm PFS (mo) MS 1 yr OS

G + C 5.7 10.2 27%

G C* 2.2 6.5 35%

* 34% of elderly and 60% of PS 2 pts were unable to start C225 maintenance or 2nd line Tx.

Gridelli C, Mencoboni M, Carrozza F et al. C225 and Gemcitabine in elderly or adult PS 2 advanced NSCLC pts : the CALC-1 randomized phase II trials. JCO 2008: 2(15S): 452s (A8117)

NCCTG: N0422: Cetuximab (C225) and RT in Elderly NCCTG: N0422: Cetuximab (C225) and RT in Elderly &/or Poor Performance Status Patients with Stage III &/or Poor Performance Status Patients with Stage III

NSCLC: A Phase II Study to Evaluate Survival & ToxicityNSCLC: A Phase II Study to Evaluate Survival & Toxicity

Eligibility:Eligibility:– >65 yrs old or younger and PS=2>65 yrs old or younger and PS=2– Stage III NSCLCStage III NSCLC– Adequate organ functionAdequate organ function

TreatmentTreatment– Cetuximab, 400 mg/mCetuximab, 400 mg/m2: 2: Day 1Day 1– Then, Cetuximab 250 mg/mThen, Cetuximab 250 mg/m2: 2: Days 8, 15, 22, 29, Days 8, 15, 22, 29,

36, 43+ concurrent RT(60 Gy/30 fxs)36, 43+ concurrent RT(60 Gy/30 fxs)

Major endpoint: survivalMajor endpoint: survival

Human CRC xenograft modelHuman CRC xenograft model

– Anti-VEGF mAb–treated animals showed significant Anti-VEGF mAb–treated animals showed significant reductions in the mean number of metastases per liver reductions in the mean number of metastases per liver

(10-fold less) and tumor volume (nearly 20-fold (10-fold less) and tumor volume (nearly 20-fold less)less)

Warren et al. J Clin Invest. 1995;95:1789–1799.

VEGF mAb Control mAb

Growth of experimental liver metastases

VEGF mAb

Control mAb

226

22

Tum

ors

per

liver

, no

.Inhibition of Tumor Vascularization:Inhibition of Tumor Vascularization:

Reduced Metastases and Tumor VolumeReduced Metastases and Tumor Volume

0

50

100

150

200

250

rhuMAb VEGF (Recombinant rhuMAb VEGF (Recombinant Humanized Monoclonal Humanized Monoclonal Antibody to VEGFAntibody to VEGF) aka ) aka

BevacizumabBevacizumabHumanized to avoid Humanized to avoid immunogenicity (93% immunogenicity (93% human, 7% murine).human, 7% murine).

Recognizes all isoforms of Recognizes all isoforms of vascular endothelial growth vascular endothelial growth factor, Kfactor, Kdd = 8 x 10 = 8 x 10-10-10 M M

Terminal half life 17-21 Terminal half life 17-21 daysdays

12 mo. 24 mo.44.4% 15.4%51.0% 22.0%

0.0

0.2

0.4

0.6

0.8

1.0

Survival by Tx ArmP

roba

bilit

y

PCPCB

P = 0.003

0 6 12 18 24 30 36

Months

Medians: 10.3, 12.3

HR: 0.80 (0.65, 0.93)

Sandler et al NEJM 12/06

E4599: Outcome*E4599: Outcome*

Arm CbP CbPB

RR % 15 35

PFS (mo) 4.5 6.2

MS (mo) 10.3 12.3

1yr OS % 43.7 51.9

2 y OS % 16.9 22.1

* All Differences were statistically significant p< 0.05

Outcomes for Elderly Advanced Stage Non-small Outcomes for Elderly Advanced Stage Non-small Cell Lung Cancer Patients Treated With Cell Lung Cancer Patients Treated With

Bevacizumab in Combination with Carboplatin and Bevacizumab in Combination with Carboplatin and Paclitaxel: Analysis of ECOG 4599 Study Paclitaxel: Analysis of ECOG 4599 Study

Abstract # 7535, ASCO ‘07Abstract # 7535, ASCO ‘07

S. RamalingamS. Ramalingam11, S. E. Dahlberg, S. E. Dahlberg22, C. J. Langer, C. J. Langer33, R. Gray, R. Gray22, C. P. , C. P. BelaniBelani11, J. R. Brahmer, J. R. Brahmer44, A. Sandler, A. Sandler55, J. H. Schiller, J. H. Schiller66, D. H. , D. H.

JohnsonJohnson55

11University of Pittsburgh Cancer Institute, Pittsburgh, PA, University of Pittsburgh Cancer Institute, Pittsburgh, PA, 22 Dana Farber Cancer Institute, Boston, MA. Dana Farber Cancer Institute, Boston, MA.

33 Fox Chase Cancer Center, Philadelphia, PA. Fox Chase Cancer Center, Philadelphia, PA.44 The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD. The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.

55 Vanderbilt-Ingram Cancer Center, Nashville, TN. Vanderbilt-Ingram Cancer Center, Nashville, TN. 66 University of Texas Southwestern Medical Center, Dallas, TX. University of Texas Southwestern Medical Center, Dallas, TX.

IntroductionIntroductionElderly patients (Elderly patients (>> 70 years) account for approximately 70 years) account for approximately 50% of all cases of lung cancer 50% of all cases of lung cancer Elderly patients with a good performance status can be Elderly patients with a good performance status can be treated with platin-based two drug combinations treated with platin-based two drug combinations Two drug combinations appear to have superior efficacy Two drug combinations appear to have superior efficacy when compared to monotherapy for the elderly when compared to monotherapy for the elderly (Lilenbaum (Lilenbaum et al, J Clin Oncol 2005; Sederholm et al J Clin Oncol 2005)et al, J Clin Oncol 2005; Sederholm et al J Clin Oncol 2005)

In general, when compared to younger patients, the In general, when compared to younger patients, the elderly have:elderly have:– Reduced hepatic and renal functionReduced hepatic and renal function– Altered volume of distributionAltered volume of distribution– More co-morbid illnessMore co-morbid illness

ObjectivesObjectivesTo compare the outcomes between carboplatin To compare the outcomes between carboplatin and paclitaxel combination (PC) chemotherapy and paclitaxel combination (PC) chemotherapy and PC with Bevacizumab (PCB) for elderly and PC with Bevacizumab (PCB) for elderly patients enrolled to ECOG 4599.patients enrolled to ECOG 4599.

To study the differences in safety and efficacy To study the differences in safety and efficacy between elderly and younger patients treated between elderly and younger patients treated with PCB in ECOG 4599with PCB in ECOG 4599

MethodsMethods

Subset analysis of ECOG 4599 databaseSubset analysis of ECOG 4599 database

Elderly patients defined as those Elderly patients defined as those >> 70 years of 70 years of age at the time of study entryage at the time of study entry

< 70 years comprised the non-elderly group< 70 years comprised the non-elderly group

Data available as of November 1, 2005 (same Data available as of November 1, 2005 (same release date as that used for the final ECOG release date as that used for the final ECOG technical report for the study)technical report for the study)

ResultsResults

Eligible cases = 850 (PC : n=433; PCB : n=417)Eligible cases = 850 (PC : n=433; PCB : n=417)>> 70 years: n=224 (26%) 70 years: n=224 (26%)>> 80 years: 1.6% 80 years: 1.6%Median age:Median age:– Non-elderly: 63 yearsNon-elderly: 63 years– Elderly: 74 yearsElderly: 74 years

Median number of cycles of therapy for patients Median number of cycles of therapy for patients >> 70 yrs 70 yrs– PC : 5 cyclesPC : 5 cycles– PCB : 7 cyclesPCB : 7 cycles

Baseline CharacteristicsBaseline Characteristics

PC PCB

< 70 yrs > 70 yrs < 70 yrs > 70 yrs

N 320 113 306 111

Female 44%* 34% 53%* 41%

PS 1 61% 60% 56% 70%

Stage IIIB 13% 12% 12% 12%

Adeno/NOS 87% 91% 87% 89%

* Indicates statistically significant difference

EfficacyEfficacyElderly (> 70) Non-Elderly (< 70)

PC PCB PC PCB

CR+PR 17% 29% 14% 36%

SD 50% 39% 50% 39%

Median PFS

4.9 m 5.9 m

P=0.063

4.4 m 6.2 m

P<0.001

1-Yr Survival

50% 46% 42% 53%

Median survival

12.1 m 11.3 m

P = 0.4

9.6 m 12.8 m

P = 0.0027

PFS in Elderly: PCB vs. PCPFS in Elderly: PCB vs. PC

Hazard ratio: 0.76 (0.57,1.01)

Overall Survival in Elderly: PCB vs. PCOverall Survival in Elderly: PCB vs. PC

Toxicity Data for Elderly PatientsToxicity Data for Elderly Patients

Worst Grade Toxicity: PC: 61%; PCB: 87% (P < 0.001)

Grade 4 PC PCB P Value

Neutropenia 22% 34% 0.06

Fever with Neutropenia 0.9% 6.2% 0.03

Thrombocytopenia 0 3.5% 0.06

Non-Hematological Toxicity in Non-Hematological Toxicity in Elderly PatientsElderly Patients

PC PCB P Value

Hypertension 0.9% 6.2% 0.03

Proteinuria 0 7.9% 0.002

Hemorrhage 1.7% 7.9% 0.03

Nausea 0 4.4% 0.03

Anorexia 0.9% 7.9% 0.01

Fatigue 12.9% 20.2% 0.16

Treatment-related Deaths among Elderly Treatment-related Deaths among Elderly PatientsPatients

PC N = 2 (1.8%)Infection (n=1)

Cardiac ischemia, Melena/GI bleeding, liver failure (n=1)

PCB N = 7 (6.3%)*Infection (n=2)

Hemoptysis (n=2)

Hematemesis (n=1)

Cerebrovascular ischemia (n=1)

Febrile neutropenia (n=1)

* P = not significant

Toxicity on PCB Arm: Elderly vs. Toxicity on PCB Arm: Elderly vs. Non-ElderlyNon-Elderly

Grade 3/4 > 70 yrs < 70 yrs P

Neutropenia (Gr 4) 34% 22% 0.02

Melena/GI Bleed 3.5% 0.9% 0.005

Proteinuria 7.9% 1.3% 0.001

Muscle weakness 7.8% 2.2% 0.02

Motor neuropathy 3.5% 0.6% 0.05

Dizziness 7.9% 1.6% 0.003

Worst Grade 87% 70% < 0.001

TRDs 6.3% 2.6% 0.08

Representation of Elderly Patients in Representation of Elderly Patients in ECOG phase III Trials for NSCLCECOG phase III Trials for NSCLC

Study N > 70 yrs Proportion MS

ECOG 5592

574 86 15% 8.5 m

ECOG 1594

1207 227 20% 8.2 m

ECOG 4599

850 224 26% 11.3 m

Conclusions: Elderly Conclusions: Elderly enrolled in E 4599enrolled in E 4599

Proportion of elderly patients on ECOG 4599 is the highest Proportion of elderly patients on ECOG 4599 is the highest recorded among ECOG phase III trials.recorded among ECOG phase III trials.PCB is associated with higher degree of toxicity in elderly PCB is associated with higher degree of toxicity in elderly patients, when compared to treatment with PC alone.patients, when compared to treatment with PC alone.No significant improvement in survival or PFS was noted with No significant improvement in survival or PFS was noted with PCB over PC for the elderly PCB over PC for the elderly (but PC out-performed historic (but PC out-performed historic controls in this study).controls in this study).When compared to younger patients, the elderly experienced When compared to younger patients, the elderly experienced more toxicity and more TRDsmore toxicity and more TRDs with PCB.with PCB.The observations are limited by the post-hoc, retrospective nature The observations are limited by the post-hoc, retrospective nature of this analysis.of this analysis.The safety and efficacy of bevacizumab-chemotherapy The safety and efficacy of bevacizumab-chemotherapy combinations in elderly patients with NSCLC merits further combinations in elderly patients with NSCLC merits further scrutiny.scrutiny.

An Open-label, Phase II Trial of An Open-label, Phase II Trial of nab-paclitaxel, Carboplatin, and nab-paclitaxel, Carboplatin, and

Bevacizumab in first-line Bevacizumab in first-line Patients with Advanced Non-Patients with Advanced Non-

Squamous Non-Small Cell Lung Squamous Non-Small Cell Lung CancerCancer

Reynolds C, Barrera D, Vu DQ, et al.

ASCO 2007, Abstract # 7610

Open label, Open label, nonrandomizednonrandomized, multicenter Phase II study. , multicenter Phase II study. Intravenous (IV) Abraxane 300 mg/m2, carboplatin IV Intravenous (IV) Abraxane 300 mg/m2, carboplatin IV AUC=6, and Bevacizumab 15 mg/kg on Day 1 of each 21-AUC=6, and Bevacizumab 15 mg/kg on Day 1 of each 21-day cycle.day cycle.Responding patients received minimum of 4 cycles of Responding patients received minimum of 4 cycles of treatment. treatment. Bevacizumab was Bevacizumab was notnot continued after completion of continued after completion of chemotherapychemotherapyPatients with progressive disease or intolerable toxicity Patients with progressive disease or intolerable toxicity came off study. Responses were assessed every two came off study. Responses were assessed every two cyclescycles

Study Design: ABX036Study Design: ABX036

Patient CharacteristicsPatient Characteristics

Overall ResponsesOverall Responses

ToxicitiesToxicities

Progression Free SurvivalProgression Free Survival

Estimated Median PFS (95% CI) 9.8 (6.1, 11.5) months

SurvivalSurvival

Median overall survival15.8 months (95% CI: 10.4, NA))

Median overall survival15.8 months (95% CI: 10.4, NA))

Combination Bevacizumab Combination Bevacizumab and Erlotinib: Results (n=40)and Erlotinib: Results (n=40)

Overall response rate 20% in 2Overall response rate 20% in 2ndnd and 3 and 3rdrd line line settingsetting

Median TTP = 7.0 monthsMedian TTP = 7.0 months– 38% FFP @ 12 mos38% FFP @ 12 mos

Median survival = 12.6 monthsMedian survival = 12.6 months

No unexpected toxicitiesNo unexpected toxicities

Herbst RS et al. J Clin Oncol. 2005;23:2544

Bevacizumab and ErlotinibBevacizumab and Erlotinib

Phase II Trial in two separate Tx-Phase II Trial in two separate Tx-naïve cohorts:naïve cohorts:– PS 2PS 2– ElderlyElderly

SchemaSchema– Erlotinib: 150 mg/dErlotinib: 150 mg/d– Bevacizumab: 10 mg/kg Q 2wksBevacizumab: 10 mg/kg Q 2wks– Tx until PD or unacceptable toxicityTx until PD or unacceptable toxicity

PI: H Borghaei, CJ Langer

Receptor Tyrosine Kinase InhibitorsReceptor Tyrosine Kinase InhibitorsInhibitor Manufacturer

VEGFR1 VEGFR2

TVEGFR3

argetPDGFR cKIT FGFR Other

Vatalanib PTK787/ZK222584

Novartis-Schering + + + + +

ZD2171 AstraZeneca + + + +

GW786034 GlaxoSmithKline + + +

Sunitinib SU11248

Pfizer / Sugen - + - + + +

AxitinibAG013736

Pfizer + + + + + -

BAY43-9006(Sorafenib) Bayer - + - +

RAF /

MEKERK

VandetanibZD6474

AstraZeneca - + - - EGFR

Efficacy Comparison for Antiangiogenic AgentsEfficacy Comparison for Antiangiogenic Agents(Without Chemotherapy)(Without Chemotherapy)

ZD6474ZD647411

SunitinibSunitinib22

SorafanibSorafanib33

ErlotinibErlotinib44

BevacizumabBevacizumab55

Docetaxel/Docetaxel/

PremetrexedPremetrexed66

ZD6474

Gefitinib

Erlotinib

Placebo

Docetaxel

Premetrexed

83

85

63

52

488

283

288

283

19

n

8.0

1.0

9.5

0.0

8.9

< 1

8.8

9.1

0.0

PR (%) SD (%)

43

59

46.4

45.8

45.0

34.0

45.0

-

NA

DCR

11.0

8.1

11.3

11.7

9.7

7.7

12.6

12.6

PFS*

-

-

-

-

-

-

-

-

-

12

Crossover

-

23.9

29.5

29.0

20.3

34.0

35.9

OS†

-

*Weeks; †Median weeks; 1Natale RB, ASCO 2006 (abstr 7000); 2Socinski AM, ASCO 2006 (abstr 7001);3Gatzemeier U, ASCO 2006 (abstr 7002); 4Shepherd FA, NEJM 353(2):123-32, 2005; 5Johnson DH, J Clin Oncol 22(11):2184-88, 2004; 6Hannah N, J Clin Oncol 22(9):158997, 2004

Early Stage NSCLC in the Early Stage NSCLC in the ElderlyElderly

Implications of the BR10 SubanalysisImplications of the BR10 Subanalysis

LACE Meta-analysisLACE Meta-analysis

Ongoing Trials evaluating Targeted Ongoing Trials evaluating Targeted TherapiesTherapies

JBR.10 JBR.10 –– Outcomes by Patient Outcomes by Patient AgeAge

T1-2, N0-1 NSCLC N2 nodes sampledN = 482

Stratified by:N0 vs N1Ras pos, neg, or unknown

Cisplatin 50 mg/m2 d1, 8Vinorelbine 30*25 mg/m2/wk x4N = 242 (*-18 excl. for Vin 30/m2) = 224 Young (≤ 65 years) = 157 Elderly (> 65 years) = 67

RANDOMIZED

No chemotherapy/ObservationN = 240 Young (≤ 65 years) = 162 Elderly (> 65 years) = 78

Pepe, J Clin Oncol. 2007 Apr 20;25(12):1553-61

JBR-10 Outcomes by AgeJBR-10 Outcomes by Age

Worse PS in olderWorse PS in older;; fewer PS0 fewer PS0 >65 >65 (53% vs 41%, = 0.01)(53% vs 41%, = 0.01)adeno>squam in younger, squam>adeno in older pts.adeno>squam in younger, squam>adeno in older pts.Patients >65 received significantly less chemoPatients >65 received significantly less chemo– no significant diffno significant diffss in toxicity, or growth factor support in toxicity, or growth factor support– mmore elderly patients refused treatmentore elderly patients refused treatment

Older patients (>75) had worst survivalOlder patients (>75) had worst survival regardless of Rx regardless of Rx, , but same when corrected for disease-specific survivalbut same when corrected for disease-specific survival

OS 46% vs. 66% for obs. vs. chemo in pts. >65OS 46% vs. 66% for obs. vs. chemo in pts. >65OS 58% vs. 70% for obs. vs. chemo in pts OS 58% vs. 70% for obs. vs. chemo in pts <<6565Benefit from chemo not seen in pts >75 (?harmful)Benefit from chemo not seen in pts >75 (?harmful)– However, patient numbers are too small to answer clearlyHowever, patient numbers are too small to answer clearly


Elderly Specific Analyses - BR10: ToxicityElderly Specific Analyses - BR10: Toxicity

Pepe et al ASCO ’06, A-7009Pepe et al ASCO ’06, A-7009

Other differences re: elderlyOther differences re: elderly– Fewer doses of VNR (p=0.014) and DDP (p=0.006)Fewer doses of VNR (p=0.014) and DDP (p=0.006)– Fewer completed Tx; more refused Tx (p=0.03)Fewer completed Tx; more refused Tx (p=0.03)– Less myalgias/arthralgias and mood alterationsLess myalgias/arthralgias and mood alterations

No significant difference with respect to other toxicities, No significant difference with respect to other toxicities, G-CSF use, and hospitalizationsG-CSF use, and hospitalizations

Cohort Young (< 65) Elderly (> 65) P value

No 150 63 NA

Mean DI - VNR 13.2 9.9 0.0004

Mean DI - DDP 18 14.1 0.001

Non Ca COD 4.8% 16.9%

BR10: Overall SurvivalBR10: Overall Survival by Age by Age GroupGroup

0 2 4 6 8 10 12

0.0

0.2

0.4

0.6

0.8

1.0

Time (Years)

Pro

bab

ility >75 N = 23

71-75 N = 48

66-70 N = 84

0-65 N = 327

0 2 4 6 8 10 12

0.0

0.2

0.4

0.6

0.8

1.0

>75 N = 23

75 N = 459

Log-Rank, p = 0.0006

H-R = 2.38

26%

63%


E1505: Phase III Trial of Adjuvant E1505: Phase III Trial of Adjuvant Chemotherapy +/- BevacizumabChemotherapy +/- Bevacizumab

RANDOMIZE

Stratification:StageHistologyGenderType of Chemo

Chemotherapy*X 4 cyclesEligibility:

#Resected IB - IIIALobectomyNo prior chemoNo planned XRTNo h/o CVA/TIANo ATE w/in 12 mo

Chemo* x 4 cycles +

Bevacizumabx 1 year

N=1500

.

*Specified regimens• Cisplatin and docetaxel• Cisplatin and vinorelbine• Cisplatin and gemcitabine• Cisplatin and pemetrexed

^ > 4 cm

• Primary endpoint: overall survival

- 1500 pts to detect 26.5 % difference in Med OS with 85% power and 2.5% type 1 significance level

• Secondary endpoints: disease-free survival, safety[bleeding and arterial thromboembolic events (ATEs)]

• Biomolecular correlatives

• No age cut-offs

Elderly patients with Advanced Elderly patients with Advanced NSCLC: Treatment PrinciplesNSCLC: Treatment Principles

Age alone should not be a criterion for treatment Age alone should not be a criterion for treatment selection in advanced diseaseselection in advanced diseasePS is the primary determinant of prognosis in PS is the primary determinant of prognosis in elderly patients with advanced NSCLCelderly patients with advanced NSCLCDedicated trials in patients aged 70 to 79 with PS Dedicated trials in patients aged 70 to 79 with PS 0-1 0-1 maymay no longer be necessary, but we have yet no longer be necessary, but we have yet to show the superiority of a platinum-based to show the superiority of a platinum-based regimen compared to a single agent in an elderly regimen compared to a single agent in an elderly specific trialspecific trialDedicated studies are urgently needed in Dedicated studies are urgently needed in octogenariansoctogenariansAssessment of co-morbidities and potential Assessment of co-morbidities and potential impact on outcome is an important research goal impact on outcome is an important research goal

Targeted Tx in Elderly Patients with Targeted Tx in Elderly Patients with Advanced NSCLC: Basic TenetsAdvanced NSCLC: Basic TenetsErlotinib as a single agent is safe and feasible in both Erlotinib as a single agent is safe and feasible in both the Tx-naïve setting and in the 2the Tx-naïve setting and in the 2ndnd/3/3rdrd line venue line venueBevacizumab in combination with standard Bevacizumab in combination with standard chemotherapy in Tx-naïve NSCLC yields chemotherapy in Tx-naïve NSCLC yields – improved OR% and a trend toward increased PFS, but improved OR% and a trend toward increased PFS, but – demonstrates no survival advantage in post-hoc analysisdemonstrates no survival advantage in post-hoc analysis– And it causes significantly more toxicity, including And it causes significantly more toxicity, including

neutropenia, FN, GI bleeding, proteinuria, motor neuropathy, neutropenia, FN, GI bleeding, proteinuria, motor neuropathy, dizziness, and TRDs.dizziness, and TRDs.

E1505, while it allows elderly pts to be enrolled, does E1505, while it allows elderly pts to be enrolled, does not permit carboplatin-based therapy.not permit carboplatin-based therapy.The role of other molecular-targeted agents and angio-The role of other molecular-targeted agents and angio-inhibitory agents merits further investigation in the inhibitory agents merits further investigation in the adjuvant setting, especially in the elderly, who are adjuvant setting, especially in the elderly, who are likely to be under-represented in current chemo-based likely to be under-represented in current chemo-based adjuvant efforts adjuvant efforts

You are never too old to sign up for this protocol !

You are never too old to You are never too old to sign up for this protocol !sign up for this protocol !

Doc, Give me the pen……..

Doc, Give me the pen……..

You are never too old to sign up for this protocol !You are never too old to You are never too old to sign up for this protocol !sign up for this protocol !

But first I have to

sign those damn HIPAA forms

But first I have to

sign those damn HIPAA forms

elderly patients with advanced nsclc: emerging role of targeted therapy

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