Original Study

Exploratory Subset Analysis of African Americans From the PointBreak Study: PemetrexedCarboplatin-Bevacizumab Followed by Maintenance Pemetrexed-Bevacizumab Versus Paclitaxel-Carboplatin-Bevacizumab Followed by Maintenance Bevacizumab in Patients With Stage IIIB/IV Nonsquamous NoneSmall-Cell Lung Cancer Craig H. Reynolds,1 Jyoti D. Patel,2 Edward B. Garon,3 Mark R. Olsen,4 Philip Bonomi,5 Ramaswamy Govindan,6 Eduardo J. Pennella,7 Jingyi Liu,7 Susan C. Guba,7 Shi Li,7 David R. Spigel,8 Robert C. Hermann,9 Mark A. Socinski,10 Coleman K. Obasaju7 Abstract The present exploratory analysis of the PointBreak trial showed no significant differences between African Americans and whites for overall survival, progression-free survival, overall response rate, or toxicity when treated with pemetrexed-carboplatin-bevacizumab and maintenance pemetrexed-bevacizumab. Consistent with the intent-to-treat population, the median overall survival was not superior for African Americans in either treatment arm. Introduction: African Americans have a greater incidence of lung cancer than whites and have been underrepresented in clinical trials. In the PointBreak trial (pemetrexed-carboplatin-bevacizumab and maintenance pemetrexedbevacizumab [PemCBev] vs. paclitaxel-carboplatin-bevacizumab and maintenance bevacizumab [PacCBev]), 10% of the patients were African American. PointBreak had negative findings; PemCBev did not demonstrate superior overall survival (OS). Materials and Methods: PointBreak subgroup efficacy and safety data were retrospectively analyzed: African Americans versus whites for PemCBev; PemCBev versus PacCBev in African Americans; and academic versus community settings for African Americans. Hazard ratios (HRs) and P values were derived from a multivariate Cox proportional hazards model after adjusting for covariates. Results: Of 939 intent-to-treat (ITT) patients, 94 were African American and 805 were white. African-American enrollment was uniform across the study sites (median, 1 African American per site). In the PemCBev arm, OS (HR, 1.125; P ¼ .525), progression-free survival (PFS)

1

US Oncology Research, Ocala, FL Northwestern University Feinberg School of Medicine, Chicago, IL 3 University of California, Los Angeles, David Geffen School of Medicine, Translational Research in Oncology-United States, Los Angeles, CA 4 Tulsa Cancer Institute, Tulsa, OK 5 Rush University Medical Center, Chicago, IL 6 Washington University School of Medicine, St Louis, MO 7 Eli Lilly and Company, Indianapolis, IN 8 Sarah Cannon Research Institute, Nashville, TN and Tennessee Oncology, PLLC, Nashville, TN 2

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9

Northwest Georgia Oncology Centers, PC, Marietta, GA Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 10

Submitted: Sep 2, 2014; Revised: Nov 9, 2014; Accepted: Nov 11, 2014; Epub: Nov 18, 2014 Address for correspondence: Craig H. Reynolds, MD, US Oncology Research, 433 SW 10 Street, Ocala FL 34471 E-mail contact: [email protected]

1525-7304/$ - see frontmatter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cllc.2014.11.004

(HR, 1.229; P ¼ .251), response (P ¼ .607), and toxicity profiles were similar in African Americans versus whites. For African Americans, OS (HR, 1.375; P ¼ .209), PFS (HR, 0.902; P ¼ .670), response (P ¼ 1.000), and toxicity profiles were similar in the PemCBev versus PacCBev arm. For African Americans, no significant differences were seen in OS (HR, 0.661; P ¼ .191) or PFS (HR, 0.969; P ¼ .915) in academic versus community practice settings. Conclusion: In the PemCBev arm, this exploratory analysis showed no significant differences between African Americans and whites for the efficacy outcomes or toxicity profiles. Consistent with the ITT population negative trial result, for African Americans, the median OS was not superior for either arm. For African Americans, PFS and OS were similar in the academic and community settings. Additional outcomes data for African Americans should be collected in lung cancer studies. Clinical Lung Cancer, Vol. 16, No. 3, 200-8 ª 2015 Elsevier Inc. All rights reserved. Keywords: Alimta, Avastin, Minority groups

Introduction The percentage of African Americans in the US population was approximately 13% in 2012.1 From 2006 to 2010 (Surveillance, Epidemiology, and End Results [SEER] Program, 18 areas), the ageadjusted male incidence of lung cancer was greater for African Americans than for whites (95.8/100,000 vs. 74.5/100,000). However, the female incidence of lung cancer was slightly lower for African Americans than for whites (52.2/100,000 vs. 54.6/100,000).2 Likewise, the age-adjusted US mortality rate from invasive lung cancer was greater for African Americans than for whites, with African American males accounting for most of this disparity.2 At diagnosis, African Americans are more likely to be younger and to present with more advanced disease than whites.3,4 From 2002 to 2008, the relative 5-year survival was lower for African Americans than for whites with localized and regional disease and for all lung cancer stages combined.5 When diagnosed with earlystage disease, African Americans are less likely than whites to receive potentially life-saving surgery.6-8 A lack of regular medical care and the presence of comorbidities has been associated with lower surgical rates among African Americans.7 African Americans with late-stage cancer are less likely to receive chemotherapy than whites for multifactorial reasons.8 The disparities in outcome between African Americans and whites, particularly among males, emphasize the need to improve the enrollment of African Americans in lung clinical trials. Historically, African Americans have been underrepresented in clinical trials.9,10 The National Institutes of Health (NIH) Revitalization Act of 1993 mandated inclusion of minorities and women in phase III NIH-funded clinical trials. This law was enacted to address disparities in clinical trial accrual11; however, racial disparities in clinical trial accrual remain. The reasons for poor accrual of African Americans into clinical trials include an inability to meet the eligibility criteria owing to comorbidities, fear of experiencing harm, distrust of the medical profession, lower education and income levels, religious beliefs, lack of access to appropriate clinical trials, and provider attitudes.12-16 Although distrust of the medical profession among African Americans has been largely blamed on the US Public Health Service Tuskegee Syphilis Study experience, the distrust is complex and multifactorial.17-19 Nonetheless, the low accruals of African Americans have made it difficult to perform subset analyses to determine whether treatment-by-ethnicity interactions exist.

PointBreak was a large randomized phase III trial that compared the efficacy and safety of pemetrexed-carboplatin-bevacizumab followed by maintenance pemetrexed-bevacizumab (PemCBev) with paclitaxel-carboplatin-bevacizumab followed by maintenance bevacizumab (PacCBev) in chemotherapy-naive patients with advanced non-squamous nonesmall-cell lung cancer (NSCLC).20 The primary endpoint of improved overall survival (OS) in the pemetrexedcontaining arm was not met in the trial. Approximately 10% of the enrolled patients in PointBreak were African American. To determine whether treatment-by-ethnicity effects were present, we performed a retrospective subset analysis of the African-American and white populations in the PointBreak trial.

Materials and Methods Patients The eligibility criteria for PointBreak have been previously described.20 The key eligibility criteria included age  18 years, measurable or nonmeasurable histologically or cytologically confirmed non-squamous NSCLC, stage IIIB with pleural effusion or stage IV (American Joint Committee on Cancer, version 6) disease,21 no previous treatment, and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. Stable, treated brain metastases were allowed. The exclusion criteria were significant vascular disease; coagulopathy; the use of full-dose anticoagulants at randomization; a history of gastrointestinal fistula, perforation, abscess, inflammatory bowel disease, or diverticulitis; a serious cardiac condition; and a history of hemoptysis within 3 months of study entry. The study was conducted in accordance with the Good Clinical Practice guidelines and the Declaration of Helsinki. Each participating center’s ethical review board approved the protocol. The patients provided written informed consent before treatment.

Study Design, Endpoints, and Treatment PointBreak (ClinicalTrials.gov identifier NCT00762034) was a multicenter, open-label, randomized, phase III trial.20 The primary endpoint was OS. The secondary endpoints included progressionfree survival (PFS), interval to progressive disease, overall response rate (ORR), and safety. Eligible patients randomly received (1:1) up to four 21-day cycles of induction therapy followed by maintenance therapy until progression or treatment discontinuation. The experimental arm received intravenous (I.V.) pemetrexed (Alimta, Eli Lilly and

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Exploratory Subset Analysis of African Americans From PointBreak Company) 500 mg/m2 plus carboplatin area under the curve (AUC) 6 plus bevacizumab (Avastin, Genentech) 15 mg/kg on day 1 as induction therapy. This was followed by I.V. pemetrexed 500 mg/m2 plus bevacizumab 15 mg/kg as maintenance therapy (PemCBev). The control arm received I.V. paclitaxel 200 mg/m2 plus carboplatin AUC 6 plus bevacizumab 15 mg/kg on day 1 as induction therapy. This was followed by I.V. bevacizumab 15 mg/kg as maintenance therapy (PacCBev). The patients received premedication in accordance with the pemetrexed and paclitaxel labeling.22,23 The pemetrexed arm also received folic acid and vitamin supplementation in accordance with the labeling.22

Statistical Analysis The efficacy and safety data from the PointBreak trial were retrospectively evaluated in the following subgroup analyses: (1) African American versus white patients in the PemCBev arm, (2) PemCBev versus PacCBev in the African American patients, and (3) academic versus community practice settings for the African American patients. The study sites that were associated with universities were considered “academic” sites, and the others were considered “community” sites. The Veterans Health Administration (VHA) hospitals were considered academic for the purposes of the present analysis. The hazard ratios (HR) and P values were derived from a multivariate Cox proportional hazards model, adjusting for disease

stage, sex, ECOG PS, and measurable and nonmeasurable disease. The response rates and adverse events (AEs) were compared using Fisher’s exact test.

Results Patient Characteristics Of the 939 intent-to-treat (ITT) patients,20 805 were white (409, PemCBev; 396 PacCBev) and 94 were African American (42 PemCBev; 52 PacCBev). In the PemCBev arm, differences were present between the whites and African Americans in sex (females, 47.9% vs. 38.1%), age ( 65 years, 49.9% vs. 71.4%), smoking status (never, 10.3% vs. 2.4%), ECOG PS (0, 43.8% vs. 33.3%), and disease stage (IIIB, 9.3% vs. 19.0%; Table 1). Of the 94 African Americans, 20 were enrolled in 13 academic centers and 74 in 38 community centers. The African American enrollment rate between the community and academic sites was similar (median, 1 African American per site).

Efficacy African Americans Versus Whites in PemCBev Arm. In the PemCBev arm, the median OS was 12.4 months (95% confidence interval [CI], 8.9-17.9) for the African Americans and 12.3 months (95% CI, 11.1-13.9) for the whites (HR, 1.125; 95% CI, 0.7831.616; P ¼ .525; Figure 1, Table 2). The median PFS was 4.6

Table 1 Baseline Characteristics of White and African American Subpopulations (Intent-to-Treat Population) PemCBev

PacCBev

White (n [ 409)

African American (n [ 42)

White (n [ 396)

African American (n [ 52)

Female

196 (47.9)

16 (38.1)

186 (47.0)

25 (48.1)

Male

213 (52.1)

26 (61.9)

210 (53.0)

27 (51.9)

65

204 (49.9)

30 (71.4)

195 (49.2)

31 (59.6)

>65

205 (50.1)

12 (28.6)

201 (50.8)

21 (40.4)

Characteristic Sex

Age (years)

Smoking status Never Ever

42 (10.3)a a

1 (2.4)

42 (10.7)b

11 (21.2)

b

366 (89.7)

41 (97.6)

351 (89.3)

41 (78.8)

0

179 (43.8)

14 (33.3)

169 (42.8)c

26 (50.0)

1

230 (56.2)

28 (66.7)

226 (57.2)c

26 (50.0)

390 (96.8)d

40 (95.2)

385 (98.7)e

47 (92.2)f

ECOG PS

Measurable disease Yes No

d

e

4 (7.8)f

13 (3.2)

2 (4.8)

5 (1.3)

38 (9.3)

8 (19.0)

36 (9.1)c

5 (9.6)

371 (90.7)

34 (81.0)

359 (90.9)c

47 (90.4)

Disease stage IIIB with pleural effusion IV

Data presented as n (%). Abbreviations: ECOG PS ¼ Eastern Cooperative Oncology Group performance status; PacCBev ¼ paclitaxel-carboplatin-bevacizumab followed by maintenance bevacizumab; PemCBev ¼ pemetrexedcarboplatin-bevacizumab followed by maintenance pemetrexed-bevacizumab. a Number of patients, 408. b Number of patients, 393. c Number of patients, 395. d Number of patients, 403. e Number of patients, 390. f Number of patients, 51.

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Craig H. Reynolds et al respectively, for the African Americans and 96.6%, 96.0%, and 100%, respectively, for the whites. During the maintenance phase, the mean dose intensity of pemetrexed and bevacizumab was 96.3% and 100.7%, respectively, for the African Americans and 95.1% and 99.4%, respectively, for the whites. During the entire study, the percentage of African American patients experiencing dose delays for pemetrexed, carboplatin, and bevacizumab was 51.2%, 29.3%, and 46.3%, respectively. The percentage of white patients was 51.0%, 26.6%, and 50.5% for pemetrexed, carboplatin, and bevacizumab, respectively. The percentage of African American patients experiencing any dose adjustment (reduction, discontinuation, omission) for pemetrexed, carboplatin, and bevacizumab was 12.2%, 9.8%, and 22.0%, respectively. The corresponding percentages were 28.9%, 20.8%, and 21.6% for the white patients. In the PemCBev arm, numeric differences were present in the incidence of some drug-related grade 1 and 2 and grade 3 and 4 AEs in the whites versus African Americans. However, with the exception of grade 3 to 4 thrombocytopenia (25.5% vs. 9.8%; P ¼ .022), none of these differences were statistically significant (Table 4).

months (95% CI, 3.1-8.2) for the African Americans and 6.0 months (95% CI, 5.6-6.9) for the whites (HR, 1.229; 95% CI, 0.864-1.749; P ¼ .251). The ORR was 38.1% (95% CI, 23.6%54.4%) for the African Americans and 33.3% (95% CI, 28.7%38.0%) for the whites (P ¼ .607). PemCBev Versus PacCBev in African Americans. For African Americans, the median OS was 12.4 months (95% CI, 8.9-17.9) with PemCBev and 13.7 months (95% CI, 10.1-16.3) with PacCBev (HR, 1.375; 95% CI, 0.837-2.258; P ¼ .209; Table 3). The median PFS was 4.6 months (95% CI, 3.1-8.2) with PemCBev and 5.1 months (95% CI, 4.3-6.3) with PacCBev (HR, 0.902; 95% CI, 0.560-1.451; P ¼ .670). The ORR was 38.1% (95% CI, 23.6%-54.4%) with PemCBev and 38.5% (95% CI, 25.3%53.0%) with PacCBev (P ¼ 1.000). African Americans in Academic Versus Community Centers. For African Americans (in both arms combined), the median OS was 16.5 months (95% CI, 10.6-26.3) in the academic sites and 11.4 months (95% CI, 9.2-14.4) in the community sites (HR, 0.661; 95% CI, 0.355-1.229; P ¼ .191). For African Americans (in both arms combined), the median PFS was 6.9 months (95% CI, 2.8-8.2) in the academic sites and 4.6 months (95% CI, 4.1-5.8) in the community sites (HR, 0.969; 95% CI, 0.544-1.726; P ¼ .915).

PemCBev Versus PacCBev in African Americans. For African Americans, some numerical differences were present in the incidence of AEs between the 2 treatment arms. However, these differences (PemCBev vs. PacCBev) were only statistically significant for drug-related grade 1 and 2 alopecia (2.4% vs. 34.0%; P < .001) and sensory neuropathy (12.2% vs. 32.0%; P ¼ .044; Table 5) and were also seen in the ITT population.20 A numerically greater incidence of grade 3 to 4

Drug Delivery and Safety African Americans Versus Whites in PemCBev Arm. During the induction phase, the mean dose intensity of pemetrexed, carboplatin, and bevacizumab was 97.8%, 94.6%, and 99.5%,

Figure 1 Overall Survival for African American (AA) Versus White (Cau) Population in the Pemetrexed-Carboplatin-Bevacizumab and Maintenance Pemetrexed-Bevacizumab (PemCBev) Arm (Intent-to-Treat Population)

1.0 0.9 0.8

Probability of Survival

Caucasian African American 12.3 (11.1-13.9) 12.4 (8.9-17.9) 1.125 (0.783-1.616) 0.525

mOS (95% CI), months Adjusted HR (95% CI) P-value

0.7 0.6 0.5 0.4 0.3 0.2 0.1

0

AA

Cau

Race

0.0

3

6

9

12

15

18

21

24

27

30

33

36

32 0

18 0

8 0

1 0

39

Months Since Randomization Risk set Cau AA

409 42

353 36

297 29

244 25

196 20

155 16

127 13

84 6

62 3

Abbreviations: CI ¼ confidence interval; HR ¼ hazard ratio; mOS ¼ median overall survival.

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Exploratory Subset Analysis of African Americans From PointBreak Table 2 Efficacy Outcomes in PemCBev Arm (Intent-to-Treat Population) PemCBev (African American vs. White) Variable

ITT (n [ 472)

African American (n [ 42)

White (n [ 409)

Adjusted HR (95% CI)

P Value

Median OS (mo)

12.6 (11.3-14.0)

12.4 (8.9-17.9)

12.3 (11.1-13.9)

1.125 (0.783-1.616)

.525a

Median PFS (mo)

6.0 (5.6-6.9)

4.6 (3.1-8.2)

6.0 (5.6-6.9)

1.229 (0.864-1.749)

.251a

34.1 (29.8-38.6)

38.1 (23.6-54.4)

33.3 (28.7-38.0)

e

.607b

Best response (%) ORR CR

0.4 (0.1-1.5)

0.0 (0.0-8.4)

0.2 (0.0-1.4)

e

e

PR

33.7 (29.4-38.1)

38.1 (23.6-54.4)

33.0 (28.5-37.8)

e

e

SD

31.8 (27.6-36.2)

21.4 (10.3-36.8)

33.3 (28.7-38.0)

e

e

PD

13.8 (10.8-17.2)

23.8 (12.1-39.5)

13.0 (9.9-16.6)

e

e

20.4

16.7

20.5

e

e

Unknown/missing

Data in parentheses are 95% CIs. Abbreviations: CI ¼ confidence interval; CR ¼ complete response; ECOG PS ¼ Eastern Cooperative Oncology Group performance status; HR ¼ hazard ratio; ITT ¼ intent-to-treat; ORR ¼ overall response rate; OS ¼ overall survival; PemCBev ¼ pemetrexed, carboplatin, and bevacizumab followed by pemetrexed and bevacizumab; PD ¼ progressive disease; PFS ¼ progression-free survival; PR ¼ partial response; SD ¼ stable disease. a P value from multivariate Cox proportional hazards model; the Cox proportional hazards model included covariates of disease stage, sex, measurable versus nonmeasurable disease, and ECOG PS. b Fisher’s exact test for African American versus white within PemCBev arm.

anemia was seen in the PemCBev arm (7.3% vs. 0.0% in the PacCBev arm), but the difference was not statistically significant (P ¼ .088).

Discussion Historically, African Americans have been underrepresented in clinical trials.9,10 The frequency of African American enrollment in PointBreak (approximately 10%) was similar to the frequency of African Americans with invasive lung and bronchus cancer in the SEER database (w10%).24 Given the disparate outcomes between African Americans and whites with advanced NSCLC, an analysis of the safety and efficacy data of the African American population in PointBreak has added to the available outcome data of African Americans with this disease. The relatively high enrollment of African Americans in PointBreak underscores the importance and

ability of study centers to enroll minority patients in both academic and community sites. Consistent with the ITT population,20 the median OS for PemCBev was not superior to that for PacCBev in African Americans enrolled in PointBreak. Likewise, among African Americans, no between-arm differences were seen for ORR and PFS. This is in contrast to the PointBreak ITT population for which the PFS was significantly longer for PemCBev than for PacCBev (HR, 0.83; 95% CI, 0.71-0.96; P ¼ .012).20 This difference might have resulted from the low patient numbers (20 African Americans enrolled at the academic centers vs. 74 African Americans at the community centers) in the present analysis, imbalances between the treatment groups among the African Americans, or other confounding variables. These issues should be considered when formulating conclusions regarding treatment effects.

Table 3 Efficacy Outcomes in African Americans (Intent-to-Treat Population) African Americans: PemCBev Versus PacCBev Variable

ITT (PemCBev; n [ 472)

ITT (PacCBev; n [ 467)

African American, PemCBev (n [ 42)

African American, PacCBev (n [ 52)

Adjusted HR (95% CI)

P Value

Median OS (mo)

12.6 (11.3-14.0)

13.4 (11.9-14.9)

12.4 (8.9-17.9)

13.7 (10.1-16.3)

1.375 (0.837-2.258)

.209a

Median PFS (mo)

6.0 (5.6-6.9)

5.6 (5.4-6.0)

4.6 (3.1-8.2)

5.1 (4.3-6.3)

0.902 (0.560-1.451)

.670a

34.1 (29.8-38.6)

33.0 (28.7-37.4)

38.1 (23.6-54.4)

38.5 (25.3-53.0)

e

1.000b

Best response (%) ORR CR

0.4 (0.1-1.5)

0.9 (0.2-2.2)

0.0 (0.0-8.4)

0.0 (0.0-6.8)

e

e

PR

33.7 (29.4-38.1)

32.1 (27.9-36.6)

38.1 (23.6-54.4)

38.5 (25.3-53.0)

e

e

SD

31.8 (27.6-36.2)

36.8 (32.4-41.4)

21.4 (10.3-36.8)

30.8 (18.7-45.1)

e

e

PD

13.8 (10.8-17.2)

10.7 (8.1-13.9)

23.8 (12.1-39.5)

17.3 (8.2-30.3)

e

e

20.4

19.4

16.7

13.5

e

e

Unknown/missing

Data in parentheses are 95% CIs. Abbreviations: CI ¼ confidence interval; ECOG PS ¼ Eastern Cooperative Oncology Group performance status; HR ¼ hazard ratio; ITT ¼ intent-to-treat; ORR ¼ overall response rate; OS ¼ overall survival; PacCBev ¼ paclitaxel, carboplatin, and bevacizumab followed by bevacizumab; PemCBev ¼ pemetrexed, carboplatin, and bevacizumab followed by pemetrexed and bevacizumab; PFS ¼ progression-free survival. a P value from multivariate Cox proportional hazards model; the Cox proportional hazards model included covariates of disease stage, sex, measurable versus nonmeasurable disease, and ECOG PS. b Fisher’s exact test for PemCBev versus PacCBev within African American subpopulation.

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Table 4 Select Possibly Drug-Related Treatment-Emergent Adverse Events in PemCBev Arm (Safety Population) PemCBev: African American Versus White

Variable

Safety (n [ 442): Grade 1-2

Safety (n [ 442): Grade 3-4

African American (n [ 41): Grade 1-2

White (n [ 384): Grade 1-2

P Valuea

African American (n [ 41): Grade 3-4

White (n [ 384): Grade 3-4

P Valuea .173

Laboratory Hemoglobin

137 (31.0)

64 (14.5)

13 (31.7)

116 (30.2)

.859

3 (7.3)

61 (15.9)

Platelets

79 (17.9)

103 (23.3)

6 (14.6)

70 (18.2)

.672

4 (9.8)

98 (25.5)

.022

Neutrophils

65 (14.7)

114 (25.8)

5 (12.2)

56 (14.6)

.817

13 (31.7)

97 (25.3)

.355

Leukocytes

54 (12.2)

31 (7.0)

4 (9.8)

48 (12.5)

.803

2 (4.9)

28 (7.3)

.755

186 (42.1)

48 (10.9)

.290

Nonlaboratory Fatigue

161 (41.9)

.620

2 (4.9)

44 (11.5)

52 (11.8)

0 (0)

5 (12.2)

44 (11.5)

.800

0 (0.0)

0 (0.0)

e

Hypertension

49 (11.1)

15 (3.4)

1 (2.4)

45 (11.7)

.107

2 (4.9)

13 (3.4)

.647

Alopecia

29 (6.6)

0 (0.0)

1 (2.4)

26 (6.8)

.498

e

e

e

Pulmonary hemorrhage

10 (2.3)

3 (0.7)

1 (2.4)

9 (2.3)

1.000

1 (2.4)

2 (0.5)

.263

GI hemorrhage

7 (1.6)

13 (2.9)

0 (0.0)

5 (1.3)

1.000

1 (2.4)

5 (1.3)

.458

Thrombosis

2 (0.5)

14 (3.2)

1 (2.4)

1 (0.3)

.184

2 (4.9)

12 (3.1)

.635

Febrile neutropenia

1 (0.2)

6 (1.4)

0 (0.0)

1 (0.3)

1.000

0 (0.0)

6 (1.6)

1.000

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Data presented as n (%). Abbreviations: GI ¼ gastrointestinal; PemCBev ¼ pemetrexed, carboplatin, and bevacizumab followed by pemetrexed and bevacizumab. a Fisher’s exact test for African American versus white.

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19 (46.3)

Sensory neuropathy

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Exploratory Subset Analysis of African Americans From PointBreak Table 5 Select Possibly Drug-Related Treatment-Emergent Adverse Events in African Americans (Safety Population) African Americans: PemCBev Versus PacCBev

Variable

PemCBev (n [ 41): Grade 1-2

PacCBev (n [ 50): Grade 1-2

P Valuea

PemCBev (n [ 41): Grade 3-4

PacCBev (n [ 50): Grade 3-4

P Valuea

Laboratory Hemoglobin

13 (31.7)

13 (26.0)

.643

3 (7.3)

0 (0.0)

.088

Platelets

6 (14.6)

8 (16.0)

1.000

4 (9.8)

2 (4.0)

.403

Neutrophils

5 (12.2)

4 (8.0)

.726

13 (31.7)

22 (44.0)

.281

Leukocytes

4 (9.8)

5 (10.0)

1.000

2 (4.9)

3 (6.0)

1.000

Nonlaboratory Fatigue Sensory neuropathy

19 (46.3)

20 (40.0)

.671

2 (4.9)

2 (4.0)

1.000

5 (12.2)

16 (32.0)

.044

0 (0.0)

2 (4.0)

1.000