Survival of Stage IIIb and IV Non-Small Cell Lung Cancer Patients on ...

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TABLES. Table 1. Type of incident trachea, bronchus and lung cancer cases by year of diagnosis and sex, Manitoba 1997-2000.
Survival of Stage IIIb and IV Non-Small Cell Lung Cancer Patients on Best Supportive Care in Manitoba, Canada

Erich Kliewer Alain Demers Sri Navaratnam Coreen Hildebrand Grace Musto

Report for AstraZeneca Canada Inc. October, 2002

TABLE OF CONTENTS

1. BACKGROUND.............................................................................................................. 1 2. METHODS....................................................................................................................... 2 2.1 Population.................................................................................................................... 2 2.2 Data ............................................................................................................................. 2 2.3 Analysis ....................................................................................................................... 3 3. RESULTS ......................................................................................................................... 4 3.1 Lung cancer in Manitoba............................................................................................. 4 3.2 Age and stage of BSC NSCLC cases .......................................................................... 5 3.3 Representativeness of BSC NSCLC cases .................................................................. 9 3.4 Chemotherapy ........................................................................................................... 10 3.5 Metastases ................................................................................................................. 17 3.6 Performance status .................................................................................................... 18 3.7 Survival ..................................................................................................................... 19 4. DISCUSSION................................................................................................................. 22 5. REFERENCES .............................................................................................................. 25

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TABLES Table 1. Type of incident trachea, bronchus and lung cancer cases by year of diagnosis and sex, Manitoba 1997-2000..................................................................................4 Table 2. Morphology of the trachea, bronchus and lung cancer cases by year of diagnosis and sex, Manitoba 1997-2000..................................................................................5 Table 3. Age at diagnosis of NSCLC cases by year of diagnosis and sex, Manitoba 1997-2000 ................................................................................................................................6 Table 4. Age at diagnosis of BSC NSCLC cases by year of diagnosis and sex, Manitoba January 1997 - June 2000 ........................................................................................7 Table 5. Stage distribution of BSC NSCLC cases by year of diagnosis and sex, Manitoba 1997 - June, 2000 ....................................................................................................8 Table 6. Stage distribution of BSC NSCLC cases by age at diagnosis and sex, Manitoba 1997 - June 2000 .....................................................................................................8 Table 7. Characteristics of all Manitoba NSCLC cases and 150 BSC NSCLC cases ....................9 Table 8. Length (days) of chemotherapy lines and time between lines........................................10 Table 9. Patients who had changes in their chemotherapy drugs by number of changes and line...................................................................................................................................10 Table 10. Reason for changing the chemotherapy drug by line ...................................................11 Table 11. Reason for stopping chemotherapy by line...................................................................11 Table 12. Type of chemotherapy by year of diagnosis and line (intent to treat) ..........................12 Table 13. Type of chemotherapy administered to the BSC NSCLC cases by stage at diagnosis and line (intent to treat)..........................................................................................13 Table 14. Distribution of chemotherapy by dose (intent to treat) and line for BSC NSCLC cases .........................................................................................................................14 Table 15. Distribution of chemotherapy by dose (intent to treat) and line for stage IIIb BSC NSCLC cases.................................................................................................................15 Table 16. Distribution of chemotherapy by dose (intent to treat) and line for stage IV BSC NSCLC cases.................................................................................................................16 Table 17. Sequence of chemotherapy treatments for the BSC NSCLC cases who received line 2 and line 3 treatments......................................................................................17 Table 18. Number of metastases in the BSC NSCLC cases by site .............................................17 Table 19. Performance status of BSC NSCLC cases....................................................................18 Table 20. Number of person-weeks accrued by BSC NSCLC cases from diagnosis date, first and last chemotherapy date and BSC date.............................................................19 Table 21. Survival of BSC NSCLC patients from diagnosis date, by stage at diagnosis and line...................................................................................................................................21 Table 22. Survival of BSC NSCLC patients from first date of chemotherapy, by stage at diagnosis and line...............................................................................................................21 Table 23. Survival of BSC NSCLC patients from last day of chemotherapy, by stage at diagnosis and line...............................................................................................................21 Table 24. Survival of BSC NSCLC patients from BSC date, by stage at diagnosis and line .........................................................................................................................................22

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FIGURES Figure 1. Age (at diagnosis) distribution of BSC NSCLC cases by sex......................................... 7 Figure 2. Survival distribution of BSC NSCLC cases by diagnosis date, dates of first and last chemotherapy and BSC date. ......................................................................................... 20

APPENDICES Appendix 1. Classification of lung cancer according to morphology ..........................................29 Appendix 2. Morphology of the trachea, bronchus and lung cancer cases diagnosed in Manitoba, 1997-2000.............................................................................................................30 Appendix 3.1 Distribution of chemotherapy according to schedule (line and cycle) for BSC NSCLC cases.................................................................................................................31 Appendix 3.2 Distribution of chemotherapy according to schedule (line and cycle) for stage IIIb BSC NSCLC cases ................................................................................................32 Appendix 3.3 Distribution of chemotherapy according to schedule (line and cycle) for stage IV BSC NSCLC cases ..................................................................................................33 Appendix 3.4 First line chemotherapy for the 17 stage IIIb and IV BSC NSCLC cases who received second line chemotherapy .......................................................................................34 Appendix 3.5 First and second line chemotherapy for the stage IV BSC NSCLC cases who received second line chemotherapy ...............................................................................35

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1. BACKGROUND Lung cancer is the second most common form of cancer in Canadian men and women and the leading cause of cancer death.1 It has been estimated that 21,200 Canadians were diagnosed with lung cancer cases in 2001.1 The two predominant types encountered are non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is a heterogeneous aggregate of distinct histological types of lung cancer, including squamous cell carcinoma, adenocarcinoma, large cell carcinoma and some rare subtypes such as adenosquamous cell carcinoma, mucoepidermoid carcinoma and adenoid cystic carcinoma. NSCLC tends to be extremely lethal and respond poorly to chemotherapy. SCLC includes pure small and large cell cancer, mixed small cell carcinoma and combined (small cell and squamous) carcinoma.2 These cancers are more responsive to chemotherapy than NSCLC.3,4 Approximately 75 to 80% of lung cancers are NSCLC 50% to 65% are of stage IIIb and IV,

7-10

2,5-7

and of these, approximately

depending on the study population. Most people

diagnosed with lung cancer die of the disease. It was reported that only 14% of Canadian men and 17% of Canadian women diagnosed with lung cancer in 1992 survived five years or more.11 Survival, however, varies considerably according to the stage at which tumors are diagnosed. While 38% to 61% of stage I lung cancer patients are expected to survive five years, only 1% of stage IV cancer patients are expected to live that long.3, 5 As noted by Dranitsaris et al.12, “The role of chemotherapy in advanced NSCLC became more clearly defined with the publication of four meta-analyses that showed a prolongation of survival after chemotherapy compared with best supportive care”.13-16 Clinical guidelines from several countries have recommended chemotherapy for stage IIIB and IV NSCLC patients who have a relatively good performance status (ECOG 0,1 and select 2).17-21 The meta-analysis by the Non-Small Cell Lung Cancer Collaborative Group indicated that late stage NSCLC patients receiving BSC plus chemotherapy had a 10% increase in one-year survival or an increased median survival of 1.5 months relative to patients on BSC only.16 According to Giaccone, the use of chemotherapy for patients with stage III NSCLC and malignant pleural effusion, or with stage IV disease, can result in a 1-year survival of about 35-40% and a median survival of approximately 9 months.22 However, once a patient has progressed on or relapsed after chemotherapy, s/he is treated with best supportive care (BSC) which usually consists of symptomatic therapy and palliative radiation in some cases. 1

This report focuses on patients diagnosed with late stage (stages IIIb and IV) NSCLC in Manitoba during the period 1997 to June, 2000 and who were receiving BSC. The objective of the report is to define the characteristics of the BSC patients and their tumors, their chemotherapy treatment prior to being placed on BSC, and their survival. A second report will examine the treatment received during BSC and will estimate the costs associated with treatment patients receive during BSC.

2. METHODS 2.1 Population Manitoba residents diagnosed with trachea, bronchus and lung cancer (ICD-9 162) between 1997 and June, 2000 were identified from the Manitoba Cancer Registry. It was possible to identify which of these cases were NSCLC from the morphology information recorded in the registry. The morphology codes used to define NSCLC cases are shown in Appendix 1. The charts of patients with NSCLC were reviewed in order to determine those who had been diagnosed at stage IIIb and had pleural effusions or supraclavicular involvement, or those who had been diagnosed at stage IV.

Of these patients, those who had been on

chemotherapy and who survived 28 or more days after their last chemotherapy were considered to be in the BSC phase of their disease. Four weeks was chosen in order to ensure the patient was no longer on chemotherapy. 2.2 Data The information for this report was derived from a variety of sources including the Manitoba Cancer Registry (MCR), the OpTx system and chart review. The MCR is legally mandated to collect information on people diagnosed with cancer in Manitoba, as well as information on their tumor and treatment. Although the MCR does include some treatment information, it is incomplete. Vital status is recorded in the registry based on death records provided by the provincial Department of Vital Statistics. The MCR has been population-based since 1956. OpTx is a software package that has been specifically developed for cancer treatment centers for the purposes of tracking patients' appointments, treatment and other health care use. 2

Patient demographic and diagnostic information is also contained in OpTx. Not all Manitoba cancer cases are included in OpTx as it is primarily used for patients seen at CancerCare Manitoba or at one of the regional sites associated with the Manitoba Community Cancer Network. In order to identify cases of NSCLC that met our BSC definition we first obtained a listing of 300 records from the Manitoba Cancer Registry that included only the NSCLC cases diagnosed in Manitoba between January 1, 1997 and December 31, 1999 and who received chemotherapy. The electronic registry abstract, progress notes, and progression screens of these 300 cases were reviewed to determine eligibility according to the study proposal (stage IIIb with either pleural effusion or supraclavicular lymph node metastasis) or stage IV (distant metastatic disease). Ninety cases did not meet these criteria. The OpTx and paper records of the resulting 210 cases were reviewed to assess BSC and to confirm staging. Cases where the staging or progression could not be confirmed by electronic record review were also included in the paper chart review. Approximately 120 cases were eligible for the study. Since we required a minimum of 150 cases, this process was repeated for lung cases diagnosed between January 1, 2000 and June 20, 2000 (approximately 100 electronic records, 40 paper records). A detailed chart review was done in four Winnipeg hospitals for 50 cases (diagnosis years 1997 through 2000) for whom insufficient data could be obtained from the CancerCare Manitoba records in order to determine BSC status. The procedure, ancillary drug, hospital/clinic admission, radiotherapy treatment, and chemotherapy dates and dosage data were abstracted from the paper and electronic records and recorded on an access database. 2.3 Analysis Survival time was measured from the initial cancer diagnosis date, from the dates of first and last chemotherapy, as well as from the time at which a patient entered into the BSC phase (i.e. had been diagnosed at stage IIIb with pleural effusions or supraclavicular involvement, or had been diagnosed at stage IV and had been on chemotherapy and had survived at least 28 days from date of last chemotherapy). The end date was either the death date, emigration date (derived form the Manitoba Health Population Registry) or the study end date of March 31, 2002. Survival was calculated by the Kaplan-Meier method using SAS v8.223. 3

3. RESULTS 3.1 Lung cancer in Manitoba In the four-year period 1997-2000 there were 3,091 new cases of trachea, bronchus and lung cancer diagnosed in Manitoba. Of these, 35 were second primaries. The cases consisted predominantly of cancers of the upper lobe (46.6%), followed by the lower lobe (23.4%). These percentages were similar for males and females (Table 1). The majority (79.7%) of these cancers were NSCLC (Table 2). The proportion of cancers that were NSCLC was similar in males (80.3%) and females (78.8%). The distribution of first primary cases by detailed morphology is provided in Appendix 2. Table 1. Type of incident trachea, bronchus and lung cancer cases by year of diagnosis and sex, Manitoba 1997-2000 1997 ICD-9

1620 1622 1623 1624 1625 1628 1629

Site

Trachea Main bronchus Upper lobe Middle lobe Lower lobe Other parts Unspecified Total

1620 1622 1623 1624 1625 1628 1629

Trachea Main bronchus Upper lobe Middle lobe Lower lobe Other parts Unspecified Total

1620 1622 1623 1624 1625 1628 1629

Trachea Main bronchus Upper lobe Middle lobe Lower lobe Other parts Unspecified Total

N 1 24 194 13 102 24 71 429 2 19 154 20 72 16 48 331 3 43 348 33 174 40 119 760

1998 %

0.2 5.6 45.2 3.0 23.8 5.6 16.6 100.0 0.6 5.7 46.5 6.0 21.8 4.8 14.5 100.0 0.4 5.7 45.8 4.3 22.9 5.3 15.7 100.0

N

-42 204 13 110 31 60 460 1 17 159 17 82 16 40 332 1 59 363 30 192 47 100 792

1999 %

N

Total1

2000 %

N

%

N

%

-9.1 44.3 2.8 23.9 6.7 13.0 100.0

Males 2 0.4 49 11.0 201 45.1 16 3.6 84 18.8 15 3.4 79 17.7 446 100.0

-27 212 14 114 9 70 446

-6.1 47.5 3.1 25.6 2.0 15.7 100.0

3 142 811 56 410 79 280 1781

0.2 8.0 45.5 3.1 23.0 4.4 15.7 100.0

0.3 5.1 47.9 5.1 24.7 4.8 12.0 100.0

Females 1 0.3 23 7.2 152 47.6 17 5.3 79 24.8 10 3.1 37 11.6 319 100.0

1 17 163 14 80 8 45 328

0.3 5.2 49.7 4.3 24.4 2.4 13.7 100.0

5 76 628 68 313 50 170 1310

0.4 5.8 47.9 5.2 23.9 3.8 13.0 100.0

0.1 7.4 45.8 3.8 24.2 5.9 12.6 100.0

Total 3 0.4 72 9.4 353 46.1 33 4.3 163 21.3 25 3.3 116 15.2 765 100.0

1 44 375 28 194 17 115 774

0.1 5.7 48.4 3.6 25.1 2.2 14.9 100.0

8 218 1439 124 723 129 450 3091

0.3 7.1 46.6 4.0 23.4 4.2 14.6 100.0

1. 3056 individuals were diagnosed with a total of 3091 primary cancers

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Table 2. Morphology of the trachea, bronchus and lung cancer cases by year of diagnosis and sex, Manitoba 1997-2000 1997 Type1

N

NSCLC SCLC Other Total NSCLC SCLC Other Total NSCLC SCLC Other Total

353 40 36 429

1998 %

82.3 9.3 8.4 100.0

N 373 51 36 460

1999 %

N

Total2

2000 %

N

%

N

%

81.1 11.1 7.8 100.0

Males 342 76.7 58 13.0 46 10.3 446 100.0

363 46 37 446

81.4 10.3 8.3 100.0

1431 195 155 1781

80.3 10.9 8.7 100.0

Females 253 79.6 41 12.9 24 7.5

258 43 27

78.7 13.1 8.2

1032 171 106

78.8 13.1 8.1

253 46 32

76.4 13.9 9.7

268 41 23

80.7 12.3 6.9

331

100.0

332

100.0

318

100.0

328

100.0

1309

100.0

80.9 11.6 7.4 100.0

Total 595 77.9 99 13.0 70 9.2 764 100.0

621 89 64 774

80.2 11.5 8.3 100.0

2463 366 261 3090

79.7 11.8 8.4 100.0

606 86 68 760

79.7 11.3 8.9 100.0

641 92 59 792

1. There was one case who had an unknown tumor type 2. 3056 individuals were diagnosed with a total of 3091 primary cancers

The majority of Manitoba NSCLC cases were males (58.1%). The age distribution of the NSCLC cases are shown in Table 3. NSCLC is concentrated in individuals over the age of 54. Compared to females (64.4%), a somewhat greater proportion of men (69.7%) were 65 years of age and over. 3.2 Age and stage of BSC NSCLC cases For the period 1997-June, 2000 we identified 150 NSCLC cases that met the criteria for the BSC case definition. The age (at diagnosis) distribution of these cases is shown in Table 4 by year of diagnosis and sex. Fifty-six percent of the BSC cases were males. The male cases tended to be older than the female cases. The majority of male BSC cases were 65-74 years of age at the time of diagnosis, whereas the majority of female cases were 55-64 years old (Figure 1). Overall, a slightly greater percentage of males (79.8%) than females (75.8%) were diagnosed at stage IV NSCLC (Table 5). However, the percentage of females diagnosed with stage IV disease has been increasing since 1997, although this is based on a relatively small number of cases.

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Table 3. Age at diagnosis of NSCLC cases by year of diagnosis and sex, Manitoba 1997-2000 1997

1998 %

N

1999 %

N

Total2

2000

Age

N

%

N

%

N

%