Still Out Living His Life Annotated by OEM65

Page 12 Back Cover Summary

STRATEGIC OVERVIEW

Annotated SALES AID

An in-depth look at the new Hycamtin Capsules campaign and sales aid

New

Demonstrate the significant survival advantage achieved when new Hycamtin Capsules is added to BSC.

The first and only FDA-approved oral chemotherapy for relapsed small cell lung cancer (SCLC) in patients with a prior complete or partial response and who are at least 45 days from the end of first-line chemotherapy

HYCAMTIN Capsules proven to significantly increase overall survival vs BSC1,2

Overall Significant Survival Advantage

KEY TOUCH POINTS: WHY

• Approximately 2x longer median survival time1,2 — 25.9 weeks median survival with Hycamtin Capsules plus BSC (95% CI, 18.3 to 31.6) vs 13.9 weeks with BSC alone (95% CI, 11.1 to 18.6) (P=0.01)

• Now that you have had a chance to discuss the clinical data, utilize this page to close the call with the HCP. Recap the particular patient type you highlighted in the beginning of the call followed by key data points and safety information

• 49% 6-month survival rate1 — 6-month survival rate was higher in the Hycamtin Capsules plus BSC group vs BSC alone (49% vs 26%) • 36% lower risk of death1,3 — Unadjusted hazard ratio for overall survival with Hycamtin Capsules was 0.64 (95% CI, 0.45 to 0.90) relative to BSC alone • u65 years—survival benefit seen in elderly patients2 — Patients u65 years of age receiving Hycamtin Capsules plus BSC showed a survival benefit vs BSC alone — Drug-related diarrhea was more frequent in patients u65 years (28%) vs those <65 years (19%)2

– Approximately double overall survival vs BSC

Hematologic and Nonhematologic Adverse Events Profile2

– 49% survival at 6 months vs 26% with BSC alone

• Grade 3/4 neutropenia, thrombocytopenia, leukopenia, and anemia were common2

– 36% lower risk of death

Convenient Oral Dosing2

• Most common grade 3/4 nonhematologic toxicities were nausea, diarrhea, vomiting, and fatigue2

Recommended Dosing2

– A survival benefit was achieved in patients ≥65 years of age

2.3 mg/m2/day once daily* for 5 consecutive days, repeated every 21 days

– Drug-related diarrhea was more frequent in elderly patients

Days 1 2 3 4 5

• Grade 3/4 hematologic and nonhematologic adverse events

21 Repeat

Please see accompanying full Prescribing Information, including BOXED WARNING.

• Dosing Recommended Dosing/ Patient Profiles

• Example: “Dr. Jones, can you see how the patient we discussed today with relapsed SCLC could benefit from NEW the convenient oral dosing and improved overall survival offered by new Hycamtin Capsules? Would you be willing to prescribe new Hycamtin Capsules for your next relapsed SCLC patient?”

* The calculated oral daily dose should be rounded to the nearest 0.25 mg. Prescribe the minimum number of 1 mg and 0.25 mg capsules. The same number of capsules should be prescribed for each of the 5 dosing days.

The Takeaway New Hycamtin Capsules is the first and only FDA-approved oral chemotherapy agent for relapsed SCLC that is proven to significantly increase survival in patients with relapsed SCLC.

This Material is for Training Purposes Only. It is not for use in Detailing or otherwise to be shown to physicians or other healthcare providers.

Page 1 Cover

Introduction With the introduction of Hycamtin Capsules, you now have an exciting new therapy to discuss with your customers. The first and only oral chemotherapy agent for patients with relapsed small cell lung cancer (SCLC), new Hycamtin Capsules approximately doubles survival time vs best supportive care (BSC), a significant amount of time for patients with a devastating and terminal disease.

Strategic OvervieW

New The first and only FDA-approved oral chemotherapy for relapsed small cell lung cancer (SCLC) in patients with a prior complete or partial response and who are at least 45 days from the end of first-line chemotherapy

Hycamtin Capsules—proven to significantly increase overall survival vs best supportive care (BSC)1,2

WHEN

This guide is intended to help you become a Hycamtin Capsules expert and valuable resource for your customers and the brand.

“ Dr. Jones, Jack is a relapsed SCLC patient with sensitive disease. He responded well to 4 courses of first-line therapy with a complete remission and was off therapy for 7 months. Using new Hycamtin Capsules as a second-line agent could help him continue to outlive his cancer and still live his life.”

STRATEGIC OVERVIEW The strategic goal is to position Hycamtin Capsules as the treatment of choice for relapsed SCLC in patients with a prior complete or partial response and who are at least 45 days from the end of first-line chemotherapy.

Generate usage of new Hycamtin Capsules by convincing customers that they can give their patients with relapsed SCLC more time to live life.

STILL OUTLIVING HIS CANCER1,2

STILL LIVING HIS LIFE1,2

Key Touch Points: WHY • First and only FDA-approved oral agent indicated for relapsed SCLC • Significant increase in survival vs BSC

The Campaign

• Patients can continue to live their lives while outliving their cancer with new Hycamtin Capsules—an effective and convenient oral chemotherapy agent

The launch campaign for new Hycamtin Capsules truly gets to the heart of what healthcare professionals (HCPs) want for their patients—extended survival. The core graphic captures an “everyday moment” that becomes particularly special in the life of a cancer patient and the headline clearly communicates the patient benefit achieved with new Hycamtin Capsules—more precious time. The bracketed graphic frames the “everyday moment” and extends on each side (like a timeline) to represent the benefit of double survival time with new Hycamtin Capsules vs BSC alone. The graphic on the cover and the survival benefit are carried throughout the sales aid, appearing at the top of each spread.

• Safety information: it is always important to make customers aware of the warnings, precautions, and side effects of new Hycamtin Capsules

Hycamtin Capsules are indicated for the treatment of relapsed SCLC in patients with a prior complete or partial response and who are at least 45 days from the end of first-line chemotherapy.

WARNING: BONE MARROW SUPPRESSION See full Prescribing Information for complete boxed warning Hycamtin Capsules should be administered only to patients with baseline neutrophil counts of ≥1,500 cells/mm3 and a platelet count ≥100,000 cells/mm3. In order to monitor the occurrence of bone marrow suppression, blood cell counts should be monitored.

NEW

Please see accompanying full Prescribing Information, including BOXED WARNING.

HOW • 2.3 mg/m2/day once a day for 5 consecutive days, repeated every 21 days

The Takeaway New Hycamtin Capsules is the first and only FDA-approved oral chemotherapy agent for relapsed SCLC that is proven to significantly increase survival in patients with relapsed SCLC.

This Material is for Training Purposes Only. It is not for use in Detailing or otherwise to be shown to physicians or other healthcare providers.

Page 2 Study Design

STRATEGIC OVERVIEW Educate customers about the pivotal trial for which new Hycamtin Capsules received approval so they appreciate the validity of the study results.

New

STRATEGIC OVERVIEW

New

The first and only FDA-approved oral The chemotherapy forFDA-approved relapsed small oral cell lung cancer (SCLC) in first and only chemotherapy for relapsed small cell lung cancer (SCLC) in patients with a prior complete or partial response whocomplete are at least daysresponse from theand endwho of are at least 45 days from the end of patients withand a prior or 45 partial first-line chemotherapy first-line chemotherapy

Hycamtin Capsules—proven to significantlyCapsules increase overall survival BSC1,2 Hycamtin —proven to vs significantly increase overall survival vs BSC1,2

• Primary end point was overall survival • Approximately one-third of patients were ≥65 years • Initially, study included patients with a treatment-free interval ≤90 days, but it was expanded to include patients with sensitive disease (TFI >90 days) • Be sure to define what was included in the BSC arm of the study as it adds validity to the study and supports the efficacy of new Hycamtin Capsules

Hycamtin Capsules + BSC (n=71)

—Majority of patients received prior —Majority therapy with cisplatin or carboplatin and etoposide ofeither patients received prior therapy with either cisplatin or carboplatin and etoposide —Patients were considered not suitable for further intravenous —Patients were considered(IV) notchemotherapy* suitable for further intravenous (IV) chemotherapy* 1 • The primary end point was overall survival (all-cause • The primary endmortality) point was overall survival (all-cause mortality)1

Characteristics

No. of patients Characteristics

Sex

52 Male 19 Female

Age, Years

TOTAL PATIENT POPULATION1,2

INITIAL INCLUSION CRITERIA1

• • • • • •

N=141 <65 years, n=97; u65 years, n=44

Extensive or limited relapsed SCLC Unsuitable for further IV chemotherapy* Refused further IV chemotherapy 1 prior chemotherapy regimen Treatment-free interval (TFI) ≤90 days Relapsed at least 45 days from the end of first-line chemotherapy

EXPANDED INCLUSION CRITERIA

• Sensitive SCLC (TFI >90 days) —Patients who refused further IV chemotherapy —Patients prohibited from further IV chemotherapy due to comorbidities

BSC Alone (n=70) EXPANDED INCLUSION CRITERIA 1

8 0 44 1 19 2

BSC Alone (n=70)

No. of patients

73 27

51 52 19 19

73 73 27 27

51 19

73 27

58.6 (43-79) 59.8 (37-76) 8.2 9.0

58.6 (43-79) 8.2

11 62 27

68 41 44 23 19

9 11 59 62 33 27

6 41 23

9 59 33

32 68

27 23 43 48

39 32 61 68

27 43

39 61

72 28

56 51 14 20

80 72 20 28

56 14

80 20

31 69 58 42

20 22 50 49 35 41 35 30

29 71 50 50

20 50 35 35

29 71 50 50

Disease Stage 23 Limited 48 Extensive Liver Metastases

No Yes

% %

Performance Status

Hycamtin Capsules + BSC1 (n=71) 1

Extensive or limited relapsed 2SCLC 2.3 mg/m /day for 5 consecutive days, 2.3 mg/m2/day for 5 consecutive days, 2 Unsuitable for further IV chemotherapy* every 21 days + BSC every 21 days + BSC Disease Stage Refused further IV chemotherapy Limited 1 prior chemotherapy regimen Extensive Treatment-free interval (TFI) ≤90 days RANDOMIZED RANDOMIZED Relapsed at least 45 days from the end Liver Metastases of first-line chemotherapy 1

No. No.ofofpatients patients

59.8 (37-76) Mean (range) SD 9.0

Performance Status

Hycamtin Capsules + BSC1 (n=71)

Age, Years

Mean (range) SD

N=141 <65 years, n=97; u65 years, n=44

BSC (n=70)

Sex

Male Female

—Analysis with Kaplan-Meier method—Analysis and comparisons using log-rank test and comparisons using log-rank test with Kaplan-Meier method

HycamtinBSC Capsules + BSC (n=70) (n=71)

Study Design/ Patient Characteristics

Overall Survival Advantage Achieved in a Phase III Clinical Trial of in a Phase III Clinical Trial of Broad Range of Patients, IncludingBroad Overall Survival Advantage Achieved ThoseRange With of Sensitive and Resistant Disease, Patients, Including Those With Sensitive and Resistant Disease, 1 1 Hycamtin Capsules Plus BSC vs BSC Alone Good and Poor Performance Status, andand Limited ExtensiveStatus, Diseaseand Hycamtin Capsules Plus BSC vs BSC Alone1 Good Poor and Performance Limited and Extensive Disease1 1 • Randomized, open-label, multicenter trial of 141 patients with multicenter relapsed SCLC • Randomized, open-label, trial of 141 patients with relapsed SCLC1

• Phase III clinical trial of new Hycamtin Capsules vs BSC

Study Design/ Patient Characteristics

KEY TOUCH POINTS: WHY

Page 3 Broad Range of Patients

51 No 20 Yes

TFI, Days† • RBC transfusions

TFI, Days

• Analgesics • RBC transfusions • Analgesics • Sensitive SCLC (TFI >90 days) • Antibiotics • Deep relaxation • Antibiotics • Deep relaxation≤60 —Patients who refused further IV therapy chemotherapy • Corticosteroids • Corticosteroids therapy >60 • Appetite stimulants • Palliative radiotherapy• Appetite stimulants • Palliative radiotherapy —Patients prohibited from further IV ≤90 Antidepressants or surgical procedures• Antidepressants or surgical procedures chemotherapy due• to comorbidities

†

22 49 41 30

>90

Median (range)

≤60 >60 ≤90 >90

84 (34-1996) Median (range)

31 69 58 42

90 (14 to 1409) 84 (34-1996)

Show customers that the trial included patients who may be less likely to benefit from chemotherapy as well as those for whom chemotherapy would be advantageous. KEY TOUCH POINTS: WHEN • Patient characteristics in Hycamtin Capsules group – Mean age of 59.8 years – Performance status 2 (27% of patients) – Extensive disease (68% of patients) – Liver metastases (28% of patients) – Treatment-free interval ≤90 days (58% of patients) • Note the questions for consideration when discussing this spread with your customers

90 (14 to 1409)

SD=standard deviation. SD=standard deviation. † Defined as time to progression since completion †of first-line chemotherapy. Defined as time to progression since completion of first-line chemotherapy.

• Safety information: it is always important to make customers aware of the warnings, precautions, and side effects of new Hycamtin Capsules

[ Questions for Consideration ]

What role does treatment-free interval play What in selecting a second-line agent? role does treatment-free interval play in selecting a second-line agent? In what situations do you provide patients with BSCsituations alone as an In what dooption? you provide patients with BSC alone as an option? What do you consider to be poor prognosticWhat factors? do you consider to be poor prognostic factors?

*Unsuitability was based on local policy concerning the unproven riskbased and benefit patients with resistant (short TFI) *Unsuitability was on localinpolicy concerning the unproven riskSCLC and and benefit in patients with resistant (short TFI) SCLC and assessed on an individual basis by the attending oncologist. assessed on an individual basis by the attending oncologist.

NEW

Please see accompanying full Prescribing Information, including BOXED WARNING. Please see accompanying full Prescribing Information, including BOXED WARNING.

[2]

[3]

[2]

[3]

The Takeaway

The phase III clinical trial of new Hycamtin Capsules vs BSC was valid and well designed.

Despite inclusion of difficult-to-treat patients, the pivotal trial for new Hycamtin Capsules demonstrated a significant survival advantage vs BSC alone.

This Material is for Training Purposes Only. It is not for use in Detailing or otherwise to be shown to physicians or other healthcare providers.

Page 4 Overall Survival Advantage

BSC alone 13.9 weeks

Approximately longerApproximately longer 1,2 median survival time1,2 median survival time Hycamtin Capsules + BSC 25.9 weeksCapsules + BSC 25.9 weeks Hycamtin • 25.9 weeks median survival•with Capsules plus BSC CI, 18.3 to 31.6) vs BSC (95% CI, 18.3 to 31.6) vs 25.9Hycamtin weeks median survival with(95% Hycamtin Capsules plus 1,2 13.9 weeks with BSC alone (95% 11.1 with to 18.6) 13.9CI, weeks BSC(P=0.01) alone (95% CI, 11.1 to 18.6) (P=0.01)1,2 Hycamtin Capsules IncreasedHycamtin 6-MonthCapsules Survival Rates When Added to BSC Rates When Added to BSC Increased 6-Month Survival 1

1 • 49% survival at 6 months with Hycamtin Capsules plus BSC 26% withCapsules BSC alone • 49% survival at 6 months withvsHycamtin plus BSC vs 26% with BSC alone1

6-Month Survival Rates

49%

Hycamtin Capsules plus BSC

6-Month Survival Rates

• Unadjusted hazard ratio for overall survival with Hycamtin was 0.64 (95% CI, 0.45Capsules to 0.90)was 0.64 (95% CI, 0.45 to 0.90) • Unadjusted hazard ratio forCapsules overall survival with Hycamtin 1,2 relative to BSC alone, indicatingrelative a 36%to lower of death (P=0.01) BSC risk alone, indicating a 36% lower risk of death (P=0.01)1,2 Kaplan-Meier Estimates for Overall Survival: Estimates for Overall Survival: Kaplan-Meier 1,2 Hycamtin Capsules Plus BSC vs Hycamtin BSC AloneCapsules Plus BSC vs BSC Alone1,2 1.0

1.0

0.8

0.6

0.4

0.2

49% 26%

• 36% lower risk of death with new Hycamtin Capsules plus BSC

0.8

Hycamtin Capsules (n=71)

BSC (n=70)

36%

Lower risk of death with Hycamtin Capsules

0.6

0.4

0.2

Overall Survival Advantage

• Safety information: it is always important to make customers aware of the warnings, precautions, and side effects of new Hycamtin Capsules

KEY TOUCH POINTS: WHY

1,2 Hycamtin Capsules AlmostHycamtin DoubledCapsules Overall Median Added to BSC Almost Survival DoubledWhen Overall Median Survival When Added to BSC1,2 Significant Overall Survival Advantage WithSurvival Hycamtin CapsulesWith Plus Hycamtin BSC1,2 Significant Overall Advantage Capsules Plus BSC1,2

Overall Survival Advantage

• 49% survival at 6 months with new Hycamtin Capsules plus BSC vs 26% with BSC alone

1,2 Hycamtin Capsules—proven to significantly increase overall vs BSC Hycamtin Capsules —proven tosurvival significantly increase overall survival vs BSC1,2

Cumulative Proportion Alive

• Approximately double overall survival vs BSC—new Hycamtin Capsules plus BSC achieved a median survival of 25.9 weeks vs only 13.9 weeks for BSC alone

Demonstrate the significant survival advantage achieved when new Hycamtin Capsules is added to BSC.

The first and only FDA-approved for relapsed small cell lung cancer (SCLC) in Theoral firstchemotherapy and only FDA-approved oral chemotherapy for relapsed small cell lung cancer (SCLC) in patients with a prior completepatients or partial response who are leastresponse 45 days from the end of least 45 days from the end of with a priorand complete or at partial and who are at first-line chemotherapy first-line chemotherapy

Cumulative Proportion Alive

KEY TOUCH POINTS: WHY

STRATEGIC OVERVIEW

New

Patients (%)

Demonstrate the significant survival advantage achieved when new Hycamtin Capsules is added to BSC.

New

Patients (%)

STRATEGIC OVERVIEW

Page 5 Overall Survival Advantage

0 24

120

24 144

48168

72192

Time (weeks)

120

144

168

192

Time (weeks)

• A survival benefit was achieved in elderly patients with new Hycamtin Capsules plus BSC • Drug-related diarrhea was more frequent in elderly patients • Note the questions for consideration when discussing this spread with customers

Study randomly assigned patients with relapsed SCLC not assigned considered as candidates for SCLC not considered as candidates for Study randomly patients with relapsed standard IV therapy to BSC alone (n=70) or Hycamtin Capsulesto(2.3 standard IV therapy BSCmg/m alone2/day, (n=70) or Hycamtin Capsules (2.3 mg/m2/day, days 1 through 5, every 21 days) plus BSCdays (n=71). 1 through 5, every 21 days) plus BSC (n=71).

26%

Survival Benefit in Elderly Patients With Hycamtin Capsules PlusWith BSC2Hycamtin Capsules Plus BSC2 Survival Benefit in Elderly Patients • Among elderly patients (u65•years), those receiving Hycamtin Capsules BSC showed Among elderly patients (u65 years), thoseplus receiving Hycamtin Capsules plus BSC showed 2 a survival benefit compared with those receiving BSC alonewith a survival benefit compared those receiving BSC alone2 BSC aloneCapsules Hycamtin plus BSC

BSC alone

— Drug-related diarrhea was more frequent in diarrhea patients was u65 more years frequent of age (28%) compared — Drug-related in patients u65with years of age (28%) compared with those <65 years of age (19%)2 those <65 years of age (19%)2

[ Questions for Consideration []Questions for Consideration ] What outcome is most importantWhat to yououtcome when treating SCLC? is mostrelapsed important to you when treating relapsed SCLC? Of the data presented from this Phase IIIdata trial,presented which do from you find Of the this most Phasecompelling? III trial, which do you find most compelling? Will these results influence how you relapsed Willtreat these results SCLC? influence how you treat relapsed SCLC? years of age)?SCLC patients (u65 years of age)? Do you have any concerns about treating elderly SCLC patients (u65 Do you have any concerns about treating elderly

NEW

Please see accompanying full PrescribingPlease Information, including BOXED WARNING. see accompanying full Prescribing Information, including BOXED WARNING.

[4]

[5] [4]

[5]

The Takeaway

New Hycamtin Capsules plus BSC approximately double overall survival vs BSC alone with almost half of the patients surviving 6 months.

New Hycamtin Capsules plus BSC provided a significant survival advantage with a 36% lower risk of death compared with BSC alone.

This Material is for Training Purposes Only. It is not for use in Detailing or otherwise to be shown to physicians or other healthcare providers.

Page 6 Hematologic AEs

STRATEGIC OVERVIEW Educate customers about the safety of new Hycamtin Capsules.

Page 7 Nonhematologic AEs

New

STRATEGIC OVERVIEW

New

Educate customers about the safety of new Hycamtin Capsules.

The first only FDA-approved oralsmall chemotherapy for relapsed The first and only FDA-approved oral and chemotherapy for relapsed cell lung cancer (SCLC) small in cell lung cancer (SCLC) in patients withresponse a prior complete response patients with a prior complete or partial and who or arepartial at least 45 daysand fromwho theare endatofleast 45 days from the end of first-line chemotherapy first-line chemotherapy 1,2 Hycamtin Capsules —proven to significantly increase overall survival vs BSC1,2 Hycamtin Capsules—proven to significantly increase overall survival vs BSC

KEY TOUCH POINTS: WHY • Hematologic toxicities associated with Hycamtin Capsules were common. Bone marrow suppression (primarily neutropenia) is the doselimiting toxicity of Hycamtin Capsules; however, neutropenia is not cumulative over time

Nonhematologic Adverse Events2 Nonhematologic Adverse Events2

• It is important to note with the HCP that nonhematologic adverse events were generally mild to moderate. Grade 3/4 nonhematologic adverse events occurred in <5% of patients

of Adverse in SCLC Patients Treated With Hycamtin Capsules Incidence (u5%) of AdverseIncidence (u5%) of Adverse in SCLC Patients Treated With Hycamtin Capsules Incidence (u5%) of AdverseIncidence Reactions(u5%) in SCLC PatientsReactions Treated With Hycamtin Capsules Reactions in SCLC PatientsReactions Treated With Hycamtin Capsules BSCStudies and in 24*†Thoracic Cancer Studies2*† BSCStudies and in 24§ll Thoracic Cancer Studies2§ll Plus BSC and in 4 ThoracicPlus Cancer Plus BSC and in 4 ThoracicPlus Cancer Adverse Reactions

Adverse Reactions Hycamtin Capsules + BSC SCLC Population (N‡=70) All Grades

Grade 3

Hycamtin Capsules + Capsules BSC Hycamtin Capsules Hycamtin SCLC Population Thoracic Cancer Population Thoracic Cancer Population ‡ ‡ (N‡=682) (N =70)(N =682)

All4Grades Grade 3 Grade Grade All 4Grades Grade All Grades 3 4 Grade

Grade 3

Adverse Reactions Hycamtin Capsules + BSC SCLC Population (N¶=70)

Adverse Reactions

Grade 4

All Grades

Grade 3

Hycamtin Capsules + BSC Hycamtin Capsules Hycamtin Capsules SCLC Population Thoracic Cancer Population Thoracic Cancer Population ¶ ¶ (N¶=682) (N =70) (N =682)

All 4GradesAll Grades Grade 3 Grade Grade All 4Grades Grade 3 4 Grade

Grade 3

Grade 4

Anemia 94%

15%

10%94%

98%15%

10% 18%

7% 98%

18%

Nausea

Nausea 27%

0% 27%

33% 1%

3%0%

0% 33%

Leukopenia25% 90%

16%90%

86%25%

16% 29%

15%86%

29%

15%

Diarrhea

Diarrhea 14%

1% 14%

22% 4%

4%1%

0.4%22%

0.4%

Neutropenia

Neutropenia 91% 28%

33%91%

83%28%

33% 24%

32%83%

24%

32%

Vomiting

Vomiting 19%

0% 19%

21% 1%

3%0%

0.4%21%

0.4%

Thrombocytopenia

Thrombocytopenia 81% 30%

7% 81%

81%30%

29%7%

6% 81%

29%

Alopecia

Alopecia 10%

0% 10%

20% 0%

0.1%0%

0% 20%

0.1%

Fatigue

Fatigue 11%

0% 11%

19% 0%

4%0%

0.1%19%

0.1%

Anorexia

Anorexia 7%

0% 7%

14% 0%

2%0%

0% 14%

Asthenia

Asthenia 3%

0% 3%

7% 0%

2%0%

0% 7%

Pyrexia 7%

0% 7%

5% 1%

1%0%

1% 5%

* The safety ofin Hycamtin Capsules been cancer evaluated in 682 patients with thoracic cancer (3 recurrent SCLC studies and 1 recurrent * The safety of Hycamtin Capsules has been evaluated 682 patients withhas thoracic (3 recurrent SCLC studies and 1 recurrent non-small cell lung cancer [NSCLC] study) who received at least 1 dose of Hycamtin Capsules. non-small cell lung cancer [NSCLC] study) who received at least 1 dose of Hycamtin Capsules. † Adverse reactions were(NCI) graded using National Adverse reactions were graded using National Cancer Institute Common ToxicityCancer Criteria.Institute (NCI) Common Toxicity Criteria. ‡ N=total number of patients treated. ‡ N=total number of patients treated.

†

• Febrile neutropenia—information from the thoracic cancer studies was included because of the smaller sample size of the SCLC trial

• Febrile neutropenia occurredHycamtin in 4% ofCapsules patients in receiving Hycamtin Capsules in the 4 thoracic • Febrile neutropenia occurred in 4% of patients receiving the 4 thoracic malignancy studies2 malignancy studies2

• Dose modifications were used in the phase III SCLC trial to manage hematologic toxicities. Note that the PI states that the median day for neutrophil, red blood cell, and platelet nadirs occurred on day 15

• Dose occurred delays of in Hycamtin occurred in commonly 20% of courses from (41)—most commonly from • Dose delays of Hycamtin Capsules 20% of Capsules courses (41)—most hematologic hematologic toxicity (25 courses, 12%) toxicity (25 courses, 12%)

1 Dose population) Modifications (SCLC study population)1 Dose Modifications (SCLC study

Pyrexia §

Dose reduction of in Hycamtin Capsules(16)—most occurred inreductions 8% of courses • Dose reduction of Hycamtin• Capsules occurred 8% of courses were (16)—most reductions were duecourses, to hematologic toxicity (13 courses, 6%) due to hematologic toxicity (13 6%)

Dose escalation of in Hycamtin occurred in 14% of courses (39) • Dose escalation of Hycamtin• Capsules occurred 14% of Capsules courses (39)

ll ¶

0% 0% 1%

The safety ofin Hycamtin Capsules been cancer evaluated in 682 patients with thoracic cancer (3 recurrent SCLC studies and 1 recurrent The safety of Hycamtin Capsules has been evaluated 682 patients withhas thoracic (3 recurrent SCLC studies and 1 recurrent NSCLC study) who received at least 1 dose of Hycamtin Capsules. NSCLC study) who received at least 1 dose of Hycamtin Capsules. ll Adverse reactions were graded using NCI Common Toxicity Criteria. Adverse reactions were graded using NCI Common Toxicity Criteria. ¶ N=total number of patients treated. N=total number of patients treated. §

References: MER, Ciuleanu T-E, Tsekov H, etcare al. Phase trialsupportive comparingcare supportive References: 1. O’Brien MER, Ciuleanu T-E, Tsekov H,1.etO’Brien al. Phase III trial comparing supportive aloneIII with with oralcare alone with supportive care with oral topotecan patients with relapsed small-cell lung cancer.2.J Hycamtin Clin Oncol.Capsules 2006;24(34):5441-5447. topotecan in patients with relapsed small-cell lung in cancer. J Clin Oncol. 2006;24(34):5441-5447. [package insert]. 2. Hycamtin Capsules [package insert]. Research Triangle Park, M, NC:Eckardt GlaxoSmithKline; 2008. 3. O’Brien M,with Eckardt J, Ramlau R. Recent advances with topotecan Research Triangle Park, NC: GlaxoSmithKline; 2008. 3. O’Brien J, Ramlau R. Recent advances topotecan in the treatment of lung cancer. Oncologist. 2007;12:1194-1204. in the treatment of lung cancer. Oncologist. 2007;12:1194-1204.

NEW

Adverse Events

Anemia Leukopenia

Adverse Events

• Grade 3/4 hematologic toxicities in SCLC population: – Anemia—15% and 10% – Leukopenia—25% and 16% – Neutropenia—28% and 33% – Thrombocytopenia—30% and 7%

KEY TOUCH POINTS: WHY 2 Hematologic Adverse Events2 Hematologic Adverse Events

• Drug-related diarrhea was more frequent in patients ≥65 years (28%) vs those <65 years (19%). The PI states that should diarrhea occur during treatment, HCPs are advised to aggressively treat it. Clinical guidelines describing the aggressive management of diarrhea include patient education and awareness, recognition of early warning signs, use of antidiarrheals and antibiotics, changes in fluid intake and diet, and a need for hospitalization. Be proactive in discussing this adverse event with the HCP

NEW

Please see accompanying Prescribing Information, including BOXED WARNING. Please see accompanying full Prescribing Information, including full BOXED WARNING.

[6]

[7] [6]

[7]

The Takeaway

The most frequently occurring grade 3/4 hematologic adverse events with new Hycamtin Capsules were neutropenia, thrombocytopenia, leukopenia, and anemia.

The most frequent grade 3/4 nonhematologic adverse events with new Hycamtin Capsules occurred in <5% of patients.

This Material is for Training Purposes Only. It is not for use in Detailing or otherwise to be shown to physicians or other healthcare providers.

Page 8 Important Safety Information

STRATEGIC OVERVIEW

New

Page 9 Important Safety Information

New

Ensure customers know the contraindications, warnings, and precautions of new Hycamtin Capsules.

The first only FDA-approved oralsmall chemotherapy for relapsed cell lung cancer (SCLC) in The first and only FDA-approved oral and chemotherapy for relapsed cell lung cancer (SCLC) small in patients with a prior complete or partial patients with a prior complete or partial response and who are at leastresponse 45 days and fromwho the are endatofleast 45 days from the end of first-line chemotherapy first-line chemotherapy

KEY TOUCH POINTS: WHY

Important Safety Information Important Safety Information

• Indication • Boxed warning: bone marrow suppression • Contraindications • Other warnings and precautions • Drug interactions • Adverse events • Always provide full prescribing information

1,2 Hycamtin Capsules —proven to significantly increase overall survival vs BSC1,2 Hycamtin Capsules—proven to significantly increase overall survival vs BSC

Indication Diarrhea, including severe diarrhea hospitalization, has been reported during treatment with Indication Diarrhea: Diarrhea, includingDiarrhea: severe diarrhea requiring hospitalization, has requiring been reported during treatment with Hycamtin are for thecell treatment of relapsed small cellalung with a prior Hycamtin Capsules are indicated for theCapsules treatment ofindicated relapsed small lung cancer in patients with priorcancer in patientsHycamtin Hycamtin Capsules. with patientsregarding prior to drug administration regarding these side effects and Capsules. Communication with patientsCommunication prior to drug administration these side effects and complete or partial and who are at 45 days from the end of first-line chemotherapy. complete or partial response and who are at leastresponse 45 days from the end of least first-line chemotherapy. proactive management of earlyofand all signs and symptoms of diarrhea is important. proactive management of early and all signs and symptoms diarrhea is important. Treatment-related diarrhea Treatment-related diarrhea is associated morbidity Should and may be life-threatening. diarrhea is associated with significant morbidity andwith maysignificant be life-threatening. diarrhea occur during Should treatment with occur during treatment with WARNING: BONE MARROW SUPPRESSION WARNING: BONE MARROW SUPPRESSION Capsules, physicians are advised to aggressively manage diarrhea. Drug-related diarrhea was more Hycamtin Capsules, physiciansHycamtin are advised to aggressively manage diarrhea. Drug-related diarrhea was more Seefor fullcomplete Prescribing Information See full Prescribing Information boxed warning for complete boxed warning frequent patients ≥65 years of age (28%) to those <65 years of age (19%). frequent in patients ≥65 years of age in (28%) compared to those <65 yearscompared of age (19%). Capsules be administered only to patients withofbaseline neutrophil counts of Hycamtin Capsules should beHycamtin administered onlyshould to patients with baseline neutrophil counts patients experience Grade 3Capsules or 4 diarrhea, the Hycamtin Capsules For patients who experience For Grade 3 or 4who diarrhea, the Hycamtin dose should be reduced by dose should be reduced by 3 3 3 and a platelet cells/mm . In orderofto monitor the occurrence of 2 ≥1,500 cells/mm count ≥100,000 cells/mm . Incount order≥100,000 to monitor the occurrence ≥1,500 cells/mm3 and a platelet for subsequent Patients withto Grade 2 diarrhea 0.4courses. mg/m2/day Patients with Grade courses. 2 diarrhea may need follow the samemay doseneed to follow the same dose 0.4 mg/m /day for subsequent bone cell marrow suppression, blood cell counts should be monitored. bone marrow suppression, blood counts should be monitored. modification guidelines. modification guidelines. Pregnancy – Pregnancy D: Hycamtin Capsules may cause fetal when administered to a pregnant – Pregnancy D: Hycamtin Capsules may cause fetal harm when administered to aharm pregnant Hycamtin Capsules arewho contraindicated inof patients severe Contraindications: HycamtinContraindications: Capsules are contraindicated in patients have a history severe who have a history of Pregnancy woman. Women of childbearing potential should bepregnant advised to avoidtherapy becoming pregnant during therapy woman. Women of childbearing potential should be advised to avoid becoming during hypersensitivity anaphylactoid to topotecan or to any of its ingredients. hypersensitivity reactions (e.g., anaphylactoidreactions reactions)(e.g., to topotecan or to reactions) any of its ingredients. with Hycamtin Capsules. with Hycamtin Hycamtin should not pregnant be used in who are or with breastfeeding, or in patients with Capsules. Hycamtin Capsules should not be used Capsules in patients who are orpatients breastfeeding, orpregnant in patients severe bone marrow depression. severe bone marrow depression.

Experience: In theHycamtin 682 patients who in received Hycamtin Capsules in the 4 thoracic cancer studies, Clinical Trials Experience: InClinical the 682Trials patients who received Capsules the 4 thoracic cancer studies,

deaths within daysmedication after the last of study for a reason other than progressive 39 deaths occurred within 3039 days afteroccurred the last dose of30 study for dose a reason othermedication than progressive and suppression Precautions:(primarily Bone marrow suppression neutropenia) is a dose-limiting Warnings and Precautions: Warnings Bone marrow neutropenia) is a (primarily dose-limiting disease; 13 of these deaths were attributed to hematologic 5 were attributed to nonhematologic 13 of these deaths were attributed to hematologic toxicity, 5 were attributed to toxicity, nonhematologic toxicity of Hycamtin Neutropenia is not cumulative on toxicity of Hycamtin Capsules. Neutropenia is notCapsules. cumulative over time. The following dataover on time. The following datadisease; toxicity, and 21 were attributed to other causes. One patient death (68 years of age) was attributed to toxicity, and 21 were attributed to other causes. One patient death (68 years of age) was attributed to myelosuppression are based on an integrated safety databasestudies from 4(Nthoracic myelosuppression are based on an integrated safety database from 4 thoracic malignancy = 682) malignancy studies (N = 682) treatment-related diarrhea andattributed one deathdiarrhea (68 years age) attributed diarrhea treatment-related diarrhea and one death (68 years of age) asof a contributory event; bothas a contributory event; both 2 /daymedian for 5 consecutive days. Thered median day for neutrophil, red using Hycamtin Capsules at 2.3 mg/m /day for 5 consecutive days. 2The day for neutrophil, using Hycamtin Capsules at 2.3 mg/m patients received Hycamtin Capsules. patients received Hycamtin Capsules. cell, on andday platelet blood cell, and platelet nadirsblood occurred 15. nadirs occurred on day 15.

Drug Interactions: P-glycoprotein inhibitors (e.g., cyclosporine A, elacridar, Drug Interactions: P-glycoprotein inhibitors (e.g., cyclosporine A, elacridar, ketoconazole, ritonavir, and ketoconazole, ritonavir, and occurred in 32% of patients with a median Neutropenia: Grade 43neutropenia cells/mm ) occurred in(<500 32% of patients3) with a median Neutropenia: Grade 4 neutropenia (<500 cells/mm saquinavir) significant increases in topotecanuse exposure. The concomitant use of P-glycoprotein saquinavir) can cause significant increasescan in cause topotecan exposure. The concomitant of P-glycoprotein duration of 7 days and was most common during course 1 of treatment duration of 7 days and was most common during course 1 of treatment (20% of patients). Infection, (20% of patients). Infection, inhibitors with Hycamtin Capsules should be avoided. inhibitors with Hycamtin Capsules should be avoided. sepsis, and febrile occurred in 17%, 2%, and Death 4% of patients, sepsis, and febrile neutropenia occurred in 17%,neutropenia 2%, and 4% of patients, respectively. due to respectively. Death due to sepsisPancytopenia occurred in 1% patients. Pancytopenia has been reported. Topotecan-induced neutropenia sepsis occurred in 1% of patients. hasofbeen reported. Topotecan-induced neutropenia (inhibitor of ABCB1with and Hycamtin ABCG2) administered with Hycamtin Capsules increased topotecan Elacridar (inhibitor of ABCB1Elacridar and ABCG2) administered Capsules increased topotecan canFatalities lead to neutropenic colitis. Fatalities duebeen to neutropenic have been reported. In patients can lead to neutropenic colitis. due to neutropenic colitis have reported. Incolitis patients exposureoftocontrol. approximately 2.5-fold of control. A (inhibitor ABCB1, ABCC1 [MRP-1], and exposure to approximately 2.5-fold Cyclosporine A (inhibitor of Cyclosporine ABCB1, ABCC1 [MRP-1], of and presenting fever, neutropenia, and a compatible pattern of abdominal pain, the possibility of presenting with fever, neutropenia, and with a compatible pattern of abdominal pain, the possibility of CYP3A4) with Hycamtin Capsules increased exposurePatients to 2- to should 3-fold of control. Patients should CYP3A4) with Hycamtin Capsules increased topotecan exposure to 2- totopotecan 3-fold of control. neutropenic colitis should beneutropenic considered. colitis should be considered. be carefully monitored for adverse reactions Hycamtinwith Capsules are administered with a drug known be carefully monitored for adverse reactions when Hycamtin Capsules arewhen administered a drug known to inhibit 3 ) occurred in 6% of patients, with athese transporters.to inhibit these transporters. Grade 4 cells/mm thrombocytopenia ) occurred(<10,000 in 6% of cells/mm patients,3with a Thrombocytopenia: Grade 4 Thrombocytopenia: thrombocytopenia (<10,000 median duration of 3 days. median duration of 3 days.

Adverseserious Events: The most common serious adverse event is myelosuppression. Adverse Events: The most common adverse event is myelosuppression.

Grade 3 or 4inanemia g/dL) occurred in 25% of patients. Anemia: Grade 3 or 4 anemiaAnemia: (<8 g/dL) occurred 25% of(<8 patients.

Safety

The most common Gradereactions 3 or 4 hematologic adverse reactions Hycamtin(61%), Capsules were neutropenia (61%), The most common Grade 3 or 4 hematologic adverse with Hycamtin Capsules werewith neutropenia leukopenia (41%), anemia (25%).non-hematologic The most common (≥10%) non-hematologic leukopenia (41%), thrombocytopenia (37%) andthrombocytopenia anemia (25%). The(37%) mostand common (≥10%) of Bone Marrow Capsules be administered only in patients Monitoring of Bone MarrowMonitoring Function: Hycamtin CapsulesFunction: should beHycamtin administered only should in patients reactions (allvomiting grades) were nausea (27%), vomiting (19%), diarrhea (14%), fatigue (11%), and alopecia adverse were nausea (27%), (19%), diarrhea (14%), fatigue (11%), and alopecia 3 3 andreactions (all grades) adverse adequate bonea marrow including baselinecells/mm neutrophil count of u1,500 cells/mm and with adequate bone marrow with reserves, including baselinereserves, neutrophil count ofa u1,500 (10%). These adverse reactions are reported only for the Hycamtin (10%).beThese adverse reactions are reported only for the Hycamtin Capsules + BSC group, N=70.Capsules + BSC group, N=70. 3 3 . Frequent monitoring of should peripheral a platelet count u100,000 cells/mm . Frequent monitoring of peripheral blood cell counts be blood cell counts should a platelet count u100,000 cells/mm instituted during treatment with Hycamtin Capsules. instituted during treatment with Hycamtin Capsules.

Patients should notcourses be treated with subsequent of Hycamtin Capsules Patients should not be treated with subsequent of Hycamtin Capsulescourses until neutrophils recover to until neutrophils recover to 3 3 3 , platelets recover to >100,000levels cells/mm , and >1,000to cells/mm >100,000 cells/mm , and hemoglobin recover tohemoglobin u9.0 g/dL levels recover to u9.0 g/dL >1,000 cells/mm3, platelets recover (with transfusion if necessary). (with transfusion if necessary). 3 associated with fever or For patients who experience severe neutropenia (neutrophils <500 cells/mm with fever or For patients who experience severe neutropenia (neutrophils <500 cells/mm3 associated 3 for 7 days or more)500 or neutropenia (neutrophils 500 to 1,000 cells/mm3 lasting beyond lasting beyond infection or lasting for 7 days infection or more) or or lasting neutropenia (neutrophils to 1,000 cells/mm 2 day the 21 of the treatment course), the Hycamtin Capsules dose should reduced by 0.4 mg/m2/day for /daybefor day 21 of the treatment course), Hycamtin Capsules dose should be reduced by 0.4 mg/m subsequent courses. Dosesifshould be similarly if the platelet count3.falls below 25,000 cells/mm3. subsequent courses. Doses should be similarly reduced the platelet count reduced falls below 25,000 cells/mm

NEW [8]

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NEW

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The Takeaway Bone marrow suppression (primarily neutropenia) is a dose-limiting toxicity of new Hycamtin Capsules. Neutropenia is not cumulative over time.

This Material is for Training Purposes Only. It is not for use in Detailing or otherwise to be shown to physicians or other healthcare providers.

Page 10 Dosing

STRATEGIC OVERVIEW Educate customers about how to dose new Hycamtin Capsules.

Pocket Inserts Case Studies

Approximately 11 months ago, Jack was diagnosed with extensive stage small cell lung cancer (hilar mass in the right upper lobe).

KEY TOUCH POINTS: HOW • 2.3 mg/m /day once a day for 5 consecutive days (pills shown not actual size) – Cycles repeat every 21 days – Two oral dosage strengths: 1 mg and 0.25 mg capsules • This information is helpful for HCPs in educating patients on how they should take Hycamtin Capsules • How to manage patients with renal impairment, grade 3/4 neutropenia, or grade 3/4 diarrhea with dose modifications • Be sure to provide HCPs with a dosing card for reference when prescribing Hycamtin Capsules

His Treatment History

Convenient Oral Dosing2

Elderly Patient With Impaired Renal Function

• Four cycles of etoposide and carboplatin with complete remission, then off therapy for 7 months

Recommended Dosing2

• May be taken with or without food2

His Current Status

• Must be swallowed whole (do not chew, crush, or divide)2 2.3 mg/m2/day once daily* for 5 consecutive days, repeated every 21 days

Days 1 2 3 4 5

Encourage customers to consider appropriate patients for whom they would prescribe new Hycamtin Capsules.

Jack Nykuns: 59-year-old grandfather, runs a successful country store.

Hycamtin Capsules—proven to significantly increase overall survival vs BSC1,2

STRATEGIC OVERVIEW

Patient With Sensitive Disease

• If the patient vomits after taking the dose of Hycamtin Capsules, the patient should not take a replacement dose2

• Relapsed with limited disease, performance status 1 • Symptoms include cough and shortness of breath

One year ago, Dave was diagnosed with small cell lung cancer (right hilar enlargement).

His Next Treatment • What treatment would you choose for Jack?

His Treatment History

21 Repeat

Dave Smith: 71-year-old decorated veteran with limited mobility.

Patient With Poor Performance Status

• What dose/schedule would you use for that treatment? • Six cycles of etoposide and carboplatin with partial response to therapy, • What type of response would you anticipate from that treatment? then off therapy for 6 months • What side effects would you anticipate from that treatment?

Sue Johnson: 47-year-old waitress, single mom of 2 daughters.

His Current Status

• Relapsed with adrenal masses, impaired renal function, performance status 2

• Symptoms include cough with hemoptysis, shortness of breath, pain in upper Sue was right chest, and fatigue

diagnosed with small cell lung cancer (4 cm left hilar mass) 7 months ago.

Dosage Adjustments2 Hycamtin Capsules is known to be excreted by the kidney, and the risk of toxic reactions to Hycamtin Capsules may be greater in patients with impaired renal function. Renal Function Impairment: a dose adjustment of Hycamtin Capsules to 1.8 mg/m2/day is predicted to adjust the area under the curve (AUC) to the normal range for patients with moderate renal impairment (CLcr = 30-49 mL/min). Insufficient data are available in patients with severe renal impairment (CLcr <30 mL/min) to provide a dosage recommendation for Hycamtin Capsules.2

His Next Treatment • What treatment, if any, would you choose Dave? Herfor Treatment

History

• What dose/schedule would you use for that treatment? • Four cycles of etoposide and carboplatin with complete remission, then off • What type of response would you anticipate from treatment? therapy forthat 3 months • What side effects would you anticipate from that treatment?

Her Current Status • Relapsed with brain metastases, performance status 2

Patients should not be treated with subsequent courses of Hycamtin until neutrophils recover to >1,000 cells/mm3, platelets recover to >100,000 cells/mm3, and hemoglobin levels recover to u9.0 g/dL (with transfusion if necessary).2

• Symptoms include recurrent cough with hemoptysis, left-sided nonexertional chest pain, and mild intermittent headache

For patients who experience severe neutropenia (neutrophils <500 cells/mm3 associated with fever or infection or lasting for 7 days or more) or neutropenia (neutrophils 500 to 1,000 cells/mm3 lasting beyond day 21 of the treatment course), the Hycamtin Capsules dose should be reduced by 0.4 mg/m2/day for subsequent courses. Doses should be similarly reduced if the platelet count falls below 25,000 cells/mm3.2

KEY TOUCH POINTS: WHEN • In addition to the patient described earlier, 2 patient profiles are included to help you paint the picture of the appropriate patients with HCPs • Patient diagnosis and treatment history • Current status, including complications, performance status, and symptoms • Questions about each patient’s next treatment that can help you engage customers in a discussion regarding appropriate use of new Hycamtin Capsules

Her Next Treatment • What treatment, if any, would you choose for Sue? • What dose/schedule would you use for that treatment? • What type of response would you anticipate from that treatment?

Grade 3 or 4 Diarrhea: the Hycamtin Capsules dose should be reduced by 0.4 mg/m2/day for subsequent courses. Patients with grade 2 diarrhea may need to follow the same dose modification guidelines.2

• What side effects would you anticipate from that treatment?

Please see accompanying full Prescribing Information, including BOXED WARNING.

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The Takeaway

The dosing of new Hycamtin Capsules is 2.3 mg/m2/day once a day for 5 consecutive days, repeated every 21 days. Special considerations and dose adjustments may be necessary for patients with renal impairment, grade 3/4 neutropenia, or grade 3/4 diarrhea.

New Hycamtin Capsules is the first and only FDA-approved oral chemotherapy agent for relapsed SCLC in patients with prior complete or partial response and who are at least 45 days from the end of first-line chemotherapy.

This Material is for Training Purposes Only. It is not for use in Detailing or otherwise to be shown to physicians or other healthcare providers.