Pertuzumab

In the open-label, randomized, phase II NeoSPHERE trial (NCT00545688),[121] 417 women with tumors that were larger than 2 cm or node-positive, and who had HER2-positive breast cancer, were randomly assigned to one of four preoperative regimens:[121][Level of evidence B3]The following results were observed:

In the open-label, randomized, phase II NeoSPHERE trial (NCT00545688),[121] 417 women with tumors that were larger than 2 cm or node-positive, and who had HER2-positive breast cancer, were randomly assigned to one of four preoperative regimens:[121][Level of evidence B3]The following results were observed:

Docetaxel plus trastuzumab.

In the open-label, randomized, phase II NeoSPHERE trial (NCT00545688),[121] 417 women with tumors that were larger than 2 cm or node-positive, and who had HER2-positive breast cancer, were randomly assigned to one of four preoperative regimens:[121][Level of evidence B3]The following results were observed:

Docetaxel plus trastuzumab and pertuzumab.

In the open-label, randomized, phase II NeoSPHERE trial (NCT00545688),[121] 417 women with tumors that were larger than 2 cm or node-positive, and who had HER2-positive breast cancer, were randomly assigned to one of four preoperative regimens:[121][Level of evidence B3]The following results were observed:

Pertuzumab plus trastuzumab.

In the open-label, randomized, phase II NeoSPHERE trial (NCT00545688),[121] 417 women with tumors that were larger than 2 cm or node-positive, and who had HER2-positive breast cancer, were randomly assigned to one of four preoperative regimens:[121][Level of evidence B3]The following results were observed:

Docetaxel plus pertuzumab.

In the open-label, randomized, phase II NeoSPHERE trial (NCT00545688),[121] 417 women with tumors that were larger than 2 cm or node-positive, and who had HER2-positive breast cancer, were randomly assigned to one of four preoperative regimens:[121][Level of evidence B3]The following results were observed:

The pCR rates were 29% for docetaxel plus trastuzumab, 46% for docetaxel plus trastuzumab and pertuzumab, 17% for pertuzumab plus trastuzumab, and 24% for docetaxel plus pertuzumab. Therefore, the highest pCR rate was seen in the preoperative treatment arm with dual HER2 blockade plus chemotherapy.

In the open-label, randomized, phase II NeoSPHERE trial (NCT00545688),[121] 417 women with tumors that were larger than 2 cm or node-positive, and who had HER2-positive breast cancer, were randomly assigned to one of four preoperative regimens:[121][Level of evidence B3]The following results were observed:

The addition of pertuzumab to the docetaxel-plus-trastuzumab combination did not appear to increase toxic effects, including the risk of cardiac adverse events.

In the open-label, randomized, phase II NeoSPHERE trial (NCT00545688),[121] 417 women with tumors that were larger than 2 cm or node-positive, and who had HER2-positive breast cancer, were randomly assigned to one of four preoperative regimens:[121][Level of evidence B3]The following results were observed:

Despite the high pCR rate observed with dual HER2 blockade plus chemotherapy, PFS and DFS rates were not improved, although the NeoSPHERE trial was not powered to detect differences in long-term efficacy outcomes.[123]

The open-label, randomized, phase II TRYPHAENA trial (NCT00976989) sought to evaluate the tolerability and activity associated with trastuzumab and pertuzumab.[124][Level of evidence B3] All 225 women with tumors that were larger than 2 cm or node positive, and who had operable, locally advanced, or inflammatory HER2-positive breast cancer, were randomly assigned to one of three preoperative regimens: The following results were observed:

The open-label, randomized, phase II TRYPHAENA trial (NCT00976989) sought to evaluate the tolerability and activity associated with trastuzumab and pertuzumab.[124][Level of evidence B3] All 225 women with tumors that were larger than 2 cm or node positive, and who had operable, locally advanced, or inflammatory HER2-positive breast cancer, were randomly assigned to one of three preoperative regimens: The following results were observed:

Concurrent FEC plus trastuzumab plus pertuzumab (×3) followed by concurrent docetaxel plus trastuzumab plus pertuzumab.

The open-label, randomized, phase II TRYPHAENA trial (NCT00976989) sought to evaluate the tolerability and activity associated with trastuzumab and pertuzumab.[124][Level of evidence B3] All 225 women with tumors that were larger than 2 cm or node positive, and who had operable, locally advanced, or inflammatory HER2-positive breast cancer, were randomly assigned to one of three preoperative regimens: The following results were observed:

FEC alone (×3) followed by concurrent docetaxel plus trastuzumab plus pertuzumab (×3).

The open-label, randomized, phase II TRYPHAENA trial (NCT00976989) sought to evaluate the tolerability and activity associated with trastuzumab and pertuzumab.[124][Level of evidence B3] All 225 women with tumors that were larger than 2 cm or node positive, and who had operable, locally advanced, or inflammatory HER2-positive breast cancer, were randomly assigned to one of three preoperative regimens: The following results were observed:

Concurrent docetaxel and carboplatin plus trastuzumab plus pertuzumab (×6).

The open-label, randomized, phase II TRYPHAENA trial (NCT00976989) sought to evaluate the tolerability and activity associated with trastuzumab and pertuzumab.[124][Level of evidence B3] All 225 women with tumors that were larger than 2 cm or node positive, and who had operable, locally advanced, or inflammatory HER2-positive breast cancer, were randomly assigned to one of three preoperative regimens: The following results were observed:

The pCR rate was equivalent across all three treatment arms: (62% for concurrent FEC plus trastuzumab plus pertuzumab followed by concurrent docetaxel plus trastuzumab plus pertuzumab; 57% for FEC alone followed by concurrent docetaxel plus trastuzumab plus pertuzumab; and 66% for concurrent docetaxel and carboplatin plus trastuzumab plus pertuzumab).

The open-label, randomized, phase II TRYPHAENA trial (NCT00976989) sought to evaluate the tolerability and activity associated with trastuzumab and pertuzumab.[124][Level of evidence B3] All 225 women with tumors that were larger than 2 cm or node positive, and who had operable, locally advanced, or inflammatory HER2-positive breast cancer, were randomly assigned to one of three preoperative regimens: The following results were observed:

All three arms were associated with a low incidence of cardiac adverse events of 5% or less.

FEC every 3 weeks for three cycles followed by paclitaxel and carboplatin every 3 weeks for six cycles. Paclitaxel was administered on days 1 and 8 and carboplatin was administered either on day 1 alone or on days 1 and 8. Trastuzumab and pertuzumab were given every 3 weeks throughout chemotherapy. Primary prophylaxis with filgrastim was not administered during the FEC portion of therapy.

Paclitaxel and carboplatin according to the same schedule for nine cycles. Trastuzumab and pertuzumab were given every 3 weeks throughout chemotherapy.

There was no statistically significant difference in the proportion of patients with pCR between the anthracycline (67%) and non-anthracycline (68%) arm.

There was no difference in the proportion of patients in each arm who underwent breast-conserving surgery.

Irrespective of hormone receptor and nodal status, 3-year EFS estimates were 92.7% in the anthracycline group and 93.6% in the non-anthracycline group. The 3-year OS estimates were 97.7% in the anthracycline group and 98.2% in the non-anthracycline group.

A decline in LVEF of 10% or more from baseline to less than 50% was more common in patients who received anthracyclines than those who did not (7.7% vs. 3.2%; P = .04).

Two patients treated with anthracyclines developed acute leukemia.

There was no difference in the proportion of patients in each arm with at least grade 2 peripheral neuropathy: 66 patients (30%) in the anthracycline arm versus 68 patients (31%) in the non-anthracycline arm.

Grade 4 neutropenia and febrile neutropenia were more common in the anthracycline arm (23 patients [10%]) than in the non-anthracycline arm (3 patients [1%], P < .0001).