2001 Highlights from: 37th Annual Meeting of the American Society of Clinical Oncology; San Francisco, California May 12–15, 2001

meeting

highlights

2001

Highlights From: 37th Annual Meeting of the American Society of Clinical Oncology San Francisco, California May 12-15, 2001 Highlights prepared by Maxine D. Fisher, PhD Reviewed by Joyce O’Shaughnessy, MD

Use of Leuprolide to Prevent Chemotherapy-Induced Amenorrhea in Young Women Undergoing Adjuvant Chemotherapy for EarlyStage Breast Cancer Premenopausal women who are treated with adjuvant chemotherapy for breast cancer are at risk for ovarian failure and its sequelae, which include chemotherapy-related amenorrhea (CRA), vasomotor and genitourinary symptoms, accelerated osteoporosis, and infertility. CRA is correlated with improved disease-free survival, especially in hormone receptor–positive, premenopausal patients. 1-3 However, premature menopause is a common toxicity of adjuvant chemotherapy in premenopausal breast cancer patients, and young women are often concerned about maintaining fertility.4 Ovarian failure and infertility are believed to be due to the effect of chemotherapy on the developing follicle. Permanent amenorrhea might be caused by exposure of developing follicles to repeated cycles of chemotherapy. In particular, doxorubicin/cyclophosphamide (AC) appears to have a significant risk of causing premature menopause in

98 • Clinical Breast Cancer July 2001

premenopausal women, with a 47% overall incidence of CRA at 1 year.5,6 Leuprolide, a gonadotropin-releasing hormone analogue, is effective in arresting hormonally driven ovarian cycling and has been shown to prevent irreversible CRA in young women with lymphoma.7 Dr. Fox and colleagues from the University of Pennsylvania Cancer Center investigated whether concomitant administration of leuprolide could prevent adjuvant chemotherapy-induced ovarian failure in premenopausal women with early-stage breast cancer. The preliminary results of this study were presented at the 37 th Annual American Society of Clinical Oncology (ASCO) Meeting held in May 2001 in San Francisco.8 Premenopausal women with operable breast cancer, who specified a desire to remain fertile, were entered on the study. Patients received depot leuprolide 3.75 mg 1 week before chemotherapy and on day 1 of each successive chemotherapy cycle. Standard anthracyclinebased chemotherapy was administered. Six patients received AC and 5 were given AC followed by paclitaxel. Hormone receptor–positive patients received tamoxifen. The characteristics of the 13 patients

are shown in Table 1. The median age of the patients was 35 years. The majority had T2 tumors (8 of 13), N1 nodal status (7 of 13), and positive hormone receptors (7 of 13). Patients were followed for a median of 36 months. Study endpoints were recovery of menstruation, breast cancer relapse, and survival. With leuprolide therapy, all patients became amenorTable 1: Characteristics of Premenopausal, Early-Stage Breast Cancer Patients Treated with Leuprolide Plus Chemotherapy (n = 13) Median Age (Range) Tumor Size

35 (26-39) Years No. of Patients (%)

T1

3 (23%)

T2

8 (61%)

Multifocal microinvasive

1 (8%)

Occult primary

1 (8%)

Nodal Status N0

5 (38%)

N1

7 (54%)

N3

1 (8%)

Hormone Receptor Status Positive

7 (54%)

Negative

6 (46%)

Table 2: Outcomes for Breast Cancer Patients Treated with Leuprolide Plus Chemotherapy Effect on Menstruation (n = 13) • Leuprolide-induced amenorrhea in all patients by cycle 3 • Recovery of menstruation in all patients 1 year after chemotherapy

sions because most women in their thirties are expected to regain ovarian function following AC chemotherapy without leuprolide. Further studies are required to determine whether leuprolide can reduce the risk of chemotherapy-associated ovarian failure. ________________________________

at the 2001 ASCO Meeting held in San Francisco and are summarized below. The objectives of this study were to determine if the addition of breast radiation to tamoxifen in elderly women (> 70 years) who had clinical stage I disease and had undergone breast conservation surgery had an impact on locoregional recurrence; overall, diseasefree, and breast cancer–specific survival; and morbidity. The study included postmenopausal women age ≥ 70 years with clinical stage I breast cancer who were previously treated with lumpectomy. Patients were required to have histologically confirmed breast cancer with a primary tumor no larger than 2 cm that was either estrogen receptor (ER) positive or of unknown receptor status. Patients were stratified by institution, age (over or under 75 years), and whether they had undergone axillary lymph node dissection. Patients were randomized to receive tamoxifen alone or breast radiation therapy plus tamoxifen. Patients in arm I received tamoxifen 20 mg/day. Patients in arm II received radiation therapy of 1.8 Gy/day to a total of 45 Gy followed by a boost of 2.0 Gy/ day to a total of 14 Gy to the tumor bed. Tamoxifen 20 mg/day was given concurrently with radiation (Figure 1). Six hundred thirty-six patients were treated in this study. Both arms were well balanced with regard to patient characteristics. Most patients were between 70 and 75 years of age. Ninetyseven percent of patients were ER positive, and 93% of patients had primary tumors ≤ 2 cm. Approximately 64% of patients did not undergo an axillary lymph node dissection.

• Median time to return of menstruation = 5 months (range, 2-12 months) Disease Status • Three patients relapsed 16, 19, and 36 months from diagnosis • One patient died of CNS relapse at 20 months Fertility (n = 4) • One healthy delivery • One miscarriage 14 months after end of chemotherapy • Two patients unsuccessful at 12 and 30 months Posttreatment Hormonal Status (n = 9) • Mean estradiol 141 pg/mL (range, 30-478 pg/mL) • Mean FSH 9.1 mIU/mL (range, 2.7-19.6 mIU/mL) Abbreviations: CNS = central nervous system; FSH = folliclestimulating hormone

rheic by the third cycle of AC chemotherapy. All 13 patients experienced restoration of regular menses with median time to return of 5 months (Table 2). Breast cancer recurred in 3 patients (23%) at 16, 19, and 36 months after diagnosis. One patient died as a result of a central nervous system relapse. Fertility results for 4 patients who tried or are trying to become pregnant are shown in Table 2. One patient had a successful delivery, one miscarried 14 months after the end of therapy, and 2 patients were unsuccessful at 12 and 30 months.

Conclusion: This study shows that administration of leuprolide to premenopausal women undergoing adjuvant chemotherapy for early-stage breast cancer might allow them to preserve ovarian function and fertility. However, the small sample size and young age of the patients does not permit definitive conclu-

Older Women with Small Breast Tumors May Not Need Postlumpectomy Breast Radiation Lumpectomy followed by breast radiation therapy is considered the standard of care for breast cancer patients with localized disease. However, the benefit of radiation therapy in elderly women with small (< 2 cm) hormone receptor– positive breast cancer has not been clearly demonstrated. These patients tend to have biologically indolent disease and could have greater morbidity with radiation therapy. However, studies have shown that, although breast radiation therapy does not improve overall survival rates, it decreases the incidence of ipsilateral breast tumor recurrence (IBTR).9,10 Dr. Hughes and colleagues from Cancer and Leukemia Group B reported the results of an Intergroup trial to determine whether breast irradiation after breast-conserving surgery significantly decreased the incidence of local recurrence and the incidence of subsequent mastectomy. This trial also investigated the effect of radiation on morbidity and overall survival in elderly women with localized breast cancer.11 The results of this study were presented Figure 1: CALGB 9343: Treatment Schema

Eligibility Criteria: • Postmenopausal women age ≥ 70 years • Previously treated with lumpectomy • Tumor size ≤ 2 cm +

• ER or unknown receptor status

Stratified by: • Institution • Age (over or under 75 years) • Axillary dissection (yes or no)

R A N D O M I Z E

Arm I Tamoxifen 20 mg p.o. once daily

Arm II Radiation therapy 1.8 Gy 5 days a week, total 45 Gy Boost 2 Gy, total 14 Gy 5 days a week Tamoxifen 20 mg p.o. once daily

(n = 636)

Clinical Breast Cancer July 2001 • 99

Meeting Highlights Table 3: CALGB 9343: Efficacy Tamoxifen

Radiation Therapy/

(n = 319)

Tamoxifen (n = 317)

Ipsilateral Breast Tumor Recurrence

6

0

0.012

Axillary Recurrence

2

0

0.15

Locoregional Recurrence

8

0

0.004

99.7%

100%

0.22

Contralateral Breast Cancers

4 (1.3%)

6 (1.9%)

NS

Distant Metastases

3 (0.9%)

3 (0.9%)

NS

2

1

NS

80.8%

84.6%

0.48

Overall Breast Preservation

Deaths Due to Breast Cancer 5-Year Overall Survival

P Value

Abbreviation: NS = not significant

The total number of locoregional recurrences in this cohort of older patients with small ER-positive breast cancers was low. Patients who received breast irradiation had an ipsilateral recurrence-free survival of 100% as compared with 96.4% of patients treated with tamoxifen alone (P = 0.012). However, of the 6 patients who developed an ipsilateral breast tumor recurrence with tamoxifen alone, only 1 required a mastectomy; the others were treated with lumpectomy and radiation therapy. Two patients died of breast cancer on the tamoxifen-alone arm compared to 1 patient who was treated with tamoxifen and radiation. Most deaths in this study were due to causes not related to breast cancer, and overall survival was not significantly different in the 2 groups (P = 0.48) (Table 3).

Conclusion: The results from this study suggest that it might be reasonable to withhold breast irradiation in elderly women with T1 ER-positive breast cancers who have undergone lumpectomy. The locoregional recurrence rate in patients treated with tamoxifen alone was very low, and most patients who had an inbreast recurrence could be successfully treated with lumpectomy and radiation, without the need for mastectomy. The addition of radiation therapy did not affect patients’ overall, distant disease-free, or breast cancer–specific survival.

100 • Clinical Breast Cancer July 2001

Patient deaths in both groups were mainly due to causes not related to breast cancer. ________________________________

Epirubicin/Docetaxel Has a Higher Objective Response Rate Than 5Fluorouracil/Epirubicin/Cyclophosphamide in Metastatic Breast Cancer The taxanes and anthracyclines are the most active agents in the treatment of metastatic breast cancer (MBC).12,13 Many investigators have sought to improve the treatment of MBC by using combinations of these classes of agents. A phase III study in previously untreated women with MBC has shown that docetaxel has superior antitumor activity compared to doxorubicin, with a response rate of 48% versus 33%, respectively.14 Epirubicin is a less cardiotoxic anthracycline that has antitumor

activity similar to doxorubicin.15 Phase I16 and phase I/II trials17 have shown the combination of docetaxel and epirubicin to be safe and effective in patients with MBC. Therefore, Dr. Bonneterre and colleagues from France conducted a randomized phase II trial comparing the combination of epirubicin/docetaxel with 5-fluorouracil/epirubicin/cyclophosphamide in previously untreated MBC patients.18 Women with at least 1 bidimensionally measurable lesion, a World Health Organization performance status (PS) ≤ 2, and adequate organ function were eligible. Permissible prior therapy included hormonal and/or radiation therapy as well as neoadjuvant and/or adjuvant chemotherapy completed at least 12 months before study entry. Prior adjuvant anthracycline treatment was allowed at the following maximum doses: doxorubicin ≤ 310 mg/m 2 and epirubicin ≤ 460 mg/m2. A total of 142 eligible patients were randomized to receive either epirubicin 75 mg/m2 and docetaxel 75 mg/m2 (ED, n = 70) or 5-fluorouracil 500 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m 2 (FEC, n = 72), as shown in Figure 2. Chemotherapy was administered on day 1 of a 21-day cycle for no more than 8 cycles on both arms. Patients on the ED arm received 3 days of corticosteroid prophylaxis to prevent fluid retention. Patients on both arms of this study were well matched for age (median, 54 years), PS (> 90%, 0-1), and prior chemotherapy (40% with previous anthracycline-based adjuvant treatment).

Figure 2: ED vs. FEC Treatment Schema

Patients with Previously Untreated Metastatic Breast Cancer

R A N D O M I Z E

ED (n = 70) Epirubicin 75 mg/m2, day 1 Docetaxel 75 mg/m2, day 1 every 3 weeks Corticosteriod prophylaxis for 3 days

FEC (n = 72) 5-Fluorouracil 500 mg/m2, day 1 Epirubicin 75 mg/m2, day 1 Cyclophosphamide 500 mg/m2, day 1 every 3 weeks

(n = 142) Abbreviations: ED = epirubicin/docetaxel; FEC = 5-fluorouracil/epirubicin/cyclophosphamide

Meeting Highlights who received FEC. Only 6.2% of patients progressed while FEC ED Treatment receiving ED treatment as 67 63 No. of Evaluable Patients compared with 13.4% on the FEC arm. Median duration of Response response was 8.8 months for ED and 7.8 months for FEC. 2 (3.0%) 2 (3.1%) Complete response The median time to progres19 (28.3%) 38 (59.4%) Partial response sion was 8.6 months for ED treatment and 6.1 months on 37 (55.2%) 20 (31.2%) Stable disease the FEC arm. The efficacy data 9 (13.4%) 4 (6.2%) Progressive disease are summarized in Table 4. 31.3% 62.5% Overall Response Rate Toxicities were manageable with both regimens. The most 7.8 months Median Duration of Response 8.8 months common grade 3/4 hemato6.1 months 8.6 months Median Time to Progression logic toxicity was neutropenia in both the ED (67%) and FEC Abbreviations: ED = epirubicin/docetaxel; FEC = 5-fluorouracil/epirubicin/ (58%) treatment groups. Fecyclophosphamide brile neutropenia occurred in The number of metastatic sites was also 18 patients (26%) on the ED arm, after similar between the 2 arms. which 12 patients received granulocyte A median of 6 cycles of therapy were colony-stimulating factor (G-CSF). No administered on each arm. Efficacy febrile neutropenia occurred on the FEC results were superior on the ED arm as arm, and 2 patients received prophycompared to the FEC arm. The overall lactic G-CSF. Nonhematologic toxiciresponse rate for patients treated with ties were mild in both arms. The most ED was 62.5% versus 31.3% for patients common adverse events are shown in Table 5. Left ventricular ejection fraction decreases of ≥ 10% or ≥ Table 5: ED vs. FEC: Toxicities 20% from baseline were more ED FEC frequent in patients receiving (n = 70) (n = 72) FEC than with ED. One patient Grade 3/4 developed congestive heart failHematologic Toxicities ure on the ED arm. Table 4: ED vs. FEC: Efficacy

47 (67%)

42 (58%)

Thrombocytopenia

2 (3%)

3 (4%)

Anemia

3 (4%)

1 (1%)

18 (26%)

0

Asthenia

8 (11%)

4 (6%)

Nausea

5 (7%)

6 (8%)

Vomiting

6 (9%)

6 (8%)

(n = 58)

(n = 56)

11 (19%)

16 (29%)

12 (21%)

16 (29%)

Neutropenia

Febrile neutropenia Grade 3/4 Nonhematologic Toxicities*

Cardiac Function Evaluation† LVEF decrease ≥ 10% (< 20%) LVEF decrease ≥ 20%

* One death occurred on the ED arm due to sepsis. † One patient developed congestive heart failure with ED. Abbreviations: ED = epirubicin/docetaxel; FEC = 5-fluorouracil/epirubicin/ cyclophosphamide; LVEF = left ventricular ejection fraction

Conclusion: This study demonstrated that docetaxel 75 mg/m2 combined with epirubicin 75 mg/m2 is a more effective regimen than FEC in patients with metastatic breast cancer. A superior overall response rate (63% versus 31%) and a longer time to progression (8.6 months versus 6.1 months) were observed with ED treatment. Both regimens were tolerable, with greater hematologic toxicity observed with ED and equivalent cardiotoxicity with both regimens. The ED regimen is promising and is being evaluated in the adjuvant setting.

Selection of Patients with FISH Yields Superior Outcomes with First-Line Trastuzumab Treatment Trastuzumab, a humanized antiHER2 monoclonal antibody, has demonstrated a 14% response rate (RR) as a single agent in the second- or thirdline treatment of patients with HER2overexpressing MBC.19 Dr. Vogel and colleagues previously reported a 26% RR for single-agent trastuzumab as firstline therapy of HER2-overexpressing MBC.20 Patients in these 2 trastuzumab monotherapy studies were evaluated for HER2 overexpression by immunohistochemistry (IHC). At the 2001 ASCO Meeting, Dr. Vogel presented the findings of a study analyzing the clinical outcome of the patients on these trials whose breast cancers had been analyzed for HER2 expression by fluorescence in situ hybridization (FISH). 21 FISH has been used to detect HER2 gene amplification with high sensitivity and specificity.22,23 Of 336 patients enrolled on the 2 trastuzumab monotherapy studies, 328 had slides available, from which 320 FISH results were obtained. The rates of FISH amplification of patients according to HER2 overexpression as determined by IHC were 92% for 3+ and 39% for 2+ overexpression. FISH-positive patients had a higher RR and clinical benefit rate with single-agent trastuzumab than did FISH-negative patients in both studies. The RRs for FISH-positive patients were 19% and 34% in the second- and first-line studies, respectively, compared with 0% and 7%, respectively, in the FISH-negative patients. When patients who had stable disease for longer than 6 months were added to responders to determine the overall clinical benefit rate, FISH-positive patients in the second- or third-line study showed a 24% clinical benefit rate compared to 0% in the FISH-negative patients. In the first-line study, this advantage was greater, with a 48% versus 10% clinical benefit rate for patients with FISHpositive versus FISH-negative breast cancer (Table 6). Breast cancer samples (n = 1190)

Clinical Breast Cancer July 2001 • 101

Meeting Highlights Table 6: Clinical Outcome by FISH Status per Study Trastuzumab Monotherapy Second- or Third-Line Therapy19

First-Line Therapy20 FISH Status

Positive

Negative

Positive

Negative

173

36

82

29

8 (5%)

0

7 (8%)

0

Partial Response

25 (14%)

0

21 (26%)

2 (7%)

Overall Response

33 (19%)

0

28 (34%)

2 (7%)

Clinical Benefit Rate*

41 (24%)

0

39 (48%)

3 (10%)

Evaluable Patients Complete Response

* Complete response + partial response + stable disease lasting over 6 months Abbreviation: FISH = fluorescence in situ hybridization

from the Cooperative Breast Cancer Tissue Resource were analyzed for HER2 expression by the IHC clinical trials assay (CTA score) and by FISH. About 20% (212 of 1190) of the patients were found to have HER2 gene amplification by FISH, and approximately 17% of these patients had IHC scores of 0/1+ and therefore would not currently qualify for trastuzumab therapy based on the IHC results. Conversely, about 10% of patients with a 3+ IHC score showed no HER2 amplification by FISH (Table 7).

Conclusion: This analysis shows that assessment of HER2 gene amplification by FISH may help to select patients for single-agent trastuzumab therapy. HER2 gene amplification is estimated to occur in approximately 20% of the population of MBC patients. A number of patients whose breast cancers are HER2 positive by IHC will prove to have

FISH-negative breast cancer and will have little benefit with trastuzumab therapy. In contrast, 17% of patients with FISH-positive breast cancer will have only a 0 or 1+ score by IHC. These studies suggest that FISH may be superior to IHC in selecting patients for trastuzumab therapy. ________________________________

No Overall Survival Benefit for Patients with Metastatic Breast Cancer Receiving High-Dose with Stem Cell Support as Compared to Standard Chemotherapy

Patients with MBC have a 10-year survival rate of less than 10%.24 Several phase II trials showed encouraging results, with promising progression-free survival (PFS) rates for MBC patients treated with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). 25-28 HowTable 7: Incidence of HER2 Gene Amplification in ever, the morbidity and transPrimary Breast Cancer (n = 1190)* plant-related mortality rates in CTA Results FISH Results these patients were higher than with standard chemotherapy and No. of Amplification No. of Amplified Score thus the question of whether or Patients (%) Rate Patients (%) not high-dose chemotherapy pro131 (11%) 89%-92% 120 (57%) 3+ vided an overall benefit to pa143 (12%) 24%-39% 56 (26%) 2+ tients with MBC remained controversial. 250 (21%) 7% 18 (8%) 1+ The results of the landmark 666 (56%) 3% 20 (9%) 0 phase III Philadelphia Intergroup trial comparing high-dose che* Cooperative Breast Cancer Tissue Resource data motherapy with ASCT to stanAbbreviations: CTA = clinical trials assay; FISH = fluorescence in situ hybridization dard chemotherapy in women

102 • Clinical Breast Cancer July 2001

with MBC was reported in 2000.29 At a median follow-up time of 37 months, there was no difference in either overall survival or PFS comparing high-dose and standard chemotherapy. A similar trial was undertaken in 1997 by the National Cancer Institute of Canada Clinical Trials Group. This trial was closed in December 2000, and the results with a median follow-up of 19 months were reported at the 2001 ASCO Meeting.30 This trial enrolled patients with MBC who had not received prior chemotherapy for metastatic disease. Initial treatment consisted of 4 cycles of induction chemotherapy. Anthracycline-naive patients were treated with either a doxorubicin- or epirubicin-containing regimen. Patients who had received prior anthracyclines were treated with a taxane-based regimen. Patients who obtained an objective response or disease stabilization with induction therapy were randomized to either continue standard chemotherapy or to receive high-dose chemotherapy with ASCT. Stratification was based on response, visceral disease, type of induction therapy, ER status, and for ER-positive patients, prior tamoxifen versus no prior tamoxifen. Patients randomized to continue standard treatment received 2 additional cycles of the same chemotherapy regimen they received as induction therapy. Then, for patients receiving an anthracycline-based regimen, treatment was continued to a total doxorubicin dose of 450 mg/m 2 or epirubicin 840 mg/m 2. For patients receiving a taxane-based regimen, the taxane as a single agent was continued for 9 cycles. Patients randomized to the high-dose arm received 2 additional cycles of induction therapy with stem cell collection followed by high-dose therapy (cyclophosphamide 1500 mg/m2/day, mitoxantrone 17.5 mg/ m2/day, and carboplatin 450 mg/m2/day all given from days -7 to -3) and ASCT (Figure 3). Three hundred seventy-nine patients were registered, 224 of whom responded to induction therapy and were randomized to high-dose or standard therapy. The patients were typical of a popula-

Meeting Highlights achieved were similar in both arms (72% and 68% in the Standard Arm high-dose and standard arms, respectively), a higher propor2 more cycles of induction therapy Stratified by: 2 tion of patients on the stanR Total doxorubicin dose of 450 mg/m or • Response to epirubicin 840 mg/m2 Induction Therapy dard arm progressed on therA induction therapy OR 4 cycles of: apy (28% versus only 3% in N • Visceral disease 9 cycles of a single-agent taxane Anthracycline based the high-dose arm) (Table 8). D • Induction therapy for anthracycline naive This was related to a statistiO regimen High-Dose Arm OR 2 more cycles of induction therapy cally significant improvement M • ER status (negative vs. Taxane based for patients positive) Stem cell collection in median PFS for patients in I previously treated with • ER positive anthracyclines the high-dose arm (1 year Z High-dose therapy: (tamoxifen vs. Cyclophosphamide 1500 mg/m2/day, days -7 to -3 versus 0.7 years, P = 0.014). E no tamoxifen) Mitoxantrone 17.5 mg/m2/day, days -7 to -3 However, the median overall (n = 224) Carboplatin 450 mg/m2/day, days -7 to -3 survival remained the same ASCT day 0 for both groups (2 years versus 2.3 years, P = 0.95, highAbbreviations: ASCT = autologous stem cell transplantation; ER = estrogen receptor; NCIC-CTG = National Cancer Institute of Canada dose versus standard chemoClinical Trials Group therapy, respectively). This tion of MBC patients, and the 2 treat- 33% had received tamoxifen. Sixtywas likely due to the greater incidence of ment arms were well balanced. The me- eight percent of patients in each arm treatment-related mortality with highdian age of the patients was 47 years, received anthracycline-based therapy. dose therapy, including 7 treatmentand all had a PS of 0 or 1. Fifty-nine per- Sixty-two percent were ER positive, related deaths. Moreover, a Cox regrescent and 63% in the high-dose and stan- with 32% of those having progressed on sion model failed to identify any patient dard arms, respectively, had received tamoxifen. subgroup that realized a significant While the overall response rates adjuvant chemotherapy, and 29% and overall survival benefit from high-dose therapy.

Figure 3: NCIC-CTG Study MA.16: Treatment Schema

Table 8: NCIC-CTG Study MA.16: Results at a Glance High-Dose Arm

Standard Arm

(n = 112)

(n = 112)

Response Rate

72%

68%

NR

Progression on Therapy

3%

28%

NR

Median Progression-Free Survival (Years)

1.0

0.7

0.014

Median Overall Survival (Years)

2.0

2.3

0.95

7

0

NR

Treatment-Related Deaths

P Value

Abbreviations: NCIC-CTG = National Cancer Institute of Canada Clinical Trials Group; NR = not reported

Conclusion: The results of this trial corroborate the findings of the Philadelphia Intergroup trial29 and demonstrate that high-dose chemotherapy and ASCT does not prolong overall survival in women with MBC. The modest increase in PFS was offset by increased treatment-related mortality due to infections, cardiotoxicity, or other complications.

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