Herceptin for Breast Cancer

What do you get after spending UR$40,000??

Source: Brian Leyland-Jones.
Trastuzumab: hopes and realities. Lancet Oncology 3:137-144. 2002.

Trastuzumab (Herceptin) is the first clinically available oncogene-targeted therapeutic agent for treatment of solid tumours. Clinical trials in patients positive for HER2 (human epidermal-growth-factor receptor 2) show that trastuzumab is effective and well tolerated; as a single-agent second-line or third-line treatment, the drug produced durable tumour responses.

Phase II trial of single-agent trastuzumab involving 222 patients:

1. Patients were treated with an initial dose of trastuzumab of 4 mg/kg followed by 2 mg/kg weekly until disease progression.
2. These women had previously received up to eight different regimens of chemotherapy, and many had visceral disease, so their prognosis was poor.

Results:

• Objective response rate was 15% overall (8 complete responses and 26 partial responses)
• The overall median duration of response was 9·1 months.
• Time to treatment failure was 11 months compared to 5.4 months observed for the previous chemotherapy regimen.

Note: Did Herceptin cure breast cancer? No. It delayed treatment failure by 5.6 months

Phase III randomised trial involving 469 patients with metastatic HER2-positive breast cancer. Patients were divided into groups receiving chemotherapy with or without trastuzumab. The chemotherapy received depended on previous adjuvant chemotherapy.

• 281 patients who had not received anthracyclines were assigned anthracyline and cyclophosphamide with or without trastuzumab,
• 188 patients who received anthracyclines previously were assigned paclitaxel with or without trastuzumab

The primary endpoint was time to disease progression. The latest analysis of data was done after 35 months of follow-up.

Results:

• The overall response rate was 50% for patients assigned trastuzumab + chemotherapy compared with 32% for those allocated chemotherapy alone.
• Patients assigned to paclitaxel + trastuzumab achieved a response rate of 41% compared with 17% for paclitaxel alone.
• Patients assigned to anthracycline + cyclophosphamide + trastuzumab achieved a response rate of 56% compared with 42% for anthracycline + cyclophosphamide alone.
• Time to progression with addition of trastuzumab to chemotherapy was 7.4 months compared to 4.6 months without trastuzumab.
• The median survival duration was 25 months for patients assigned chemotherapy + trastuzumab compared with 20 months for those allocated chemotherapy alone – equivalent to a 25% increase in survival.

The median survival duration was 25 months for patients assigned chemotherapy + trastuzumab compared with 20 months for those allocated chemotherapy alone – equivalent to a 25% increase in survival.

The trial showed that the addition of trastuzumab to chemotherapy sunstantially prolongs survival duration in metastatic breast cancer compared with chemotherapy alone.

This is what you get for spending US$40,000 for the treatment.

a) The research result showed that with Herceptin survival was increased by 25%.

Let us look at the figures critically. The median survival duration was 25 months for patients assigned chemotherapy + trastuzumab compared with 20 months for those allocated chemotherapy alone.

The increase in survival was only 5 months. It sounds better if we say 25% rather than 5 months.

b) The research result showed that with Herceptin survival was increased by 45%.

Median survival with trastuzumab + chemotherapy = 29 months
Median survival with chemotherapy only = 20 months.
Increase of survival time = 9 months.

This is translated as increased survival by 45%.

c) The research result showed that with Herceptin survival was increased by 40%.

Median survival with trastuzumab + paclitaxel = 25 months
Median survival with paclitaxel alone = 18 months
Increase of survival time = 7 months.

This is translated as increased survival by 40%.

Greater Incidence of Heart Failure with Herceptin

Source: Department of Health Research Finding Register
The clinical effectiveness of trastuzumab for breast cancer: a systematic review. Miss Ruth Lewis 8 August 2002

There was a significantly greater incidence of congestive heart failure reported among those receiving trastuzumab plus chemotherapy compared to those on chemotherapy alone. The incidence seemed to be highest with trastuzumab plus anthracycline, rather than with trastuzumab plus paclitaxel.

Delayed Disease Progression

by 2 - 4 Months but Increased Heart Toxicity
Source: Medscape

An interesting summary concerning the role of Herceptin following chemotherapy in women with metastatic breast cancer was presented by Dr. Mark Pegram of the University of California, Los Angeles.

Women were randomly allocated to receive:

• either doxorubicin/epirubicin + cyclophosphamide (AC) alone or AC + Herceptin if they had not received previous AC.
• Women who had received previous AC were allocated to paclitaxel (T) or paclitaxe Herceptin.

Response to treatment are shown in Table below:

• The response rate was superior for Herceptin and chemotherapy overall and for Herceptin aded to AC and to Taxol.

• Time to progression was also superior, as was overall survival, when Herceptin was added to chemotherapy.However, there was considerably increased cardiac toxicity in patients treated with doxorubicin, cyclophosphamide, and Herceptin. Thus, it seems that Herceptin adds significantly to the response rate, time to progression, and overall survival in women receiving either Taxol or doxorubicin/epirubicin plus cyclophosphamide, but that because of the greatly increased cardiotoxicity.

• Herceptin and this combination should not be considered as standard therapy for women with metastatic breast cancer.