P1-12-10: Phase II Study Evaluating Lapatinib (L) in Combination with Albumin Bound Paclitaxel (ab-Pac) in Women Who Have Received 0–1 Chemotherapy Regimen for HER2 Overexpressing (HER2+) Metastatic Breast Cancer (MBC).

Document Type

Article

Department

Haematology and Oncology, East Africa

Abstract

Background: L, a dual kinase inhibitor of epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor-2 (HER2), approved for the treatment of HER2+ MBC in combination with capecitabine following progression after trastuzumab, anthracycline, and taxane. L in combination with chemotherapy has significantly improved progression free survival in patients (pts) with HER2+ MBC. Ab-Pac is a cremophor free, albumin-bound paclitaxel approved for use in pts with MBC demonstrating superior efficacy and safety when compared to other taxanes.

Methods: Phase II study (LPT111111) evaluated the efficacy and safety of L in combination with ab-Pac in 60 pts with histologically confirmed stage IV HER2+ (IHC 3+/FISH+) invasive MBC. Pts received 0–1 prior chemotherapeutic regimen in the metastatic setting and no prior treatment with L. Prior taxane therapy permitted provided this was > 12 months prior to study entry, LVEF>50%, peripheral neuropathy < 2, prior CNS mets permitted, and prior endocrine therapy permitted. Pts received ab-Pac (125 mg/m2 IV on Days 1, 8, 15, q28 days) plus L (1250 mg daily). Planned safety analysis of the first 5 pts prompted a protocol amendment with a 20% dose reduction for both agents due to Grade (G) 3 neutropenia and diarrhea. Subsequent pts received ab-Pac (100 mg/m2 IV on Day 1, 8, 15, q28 days) in combination with L (1000 mg daily). Pts with SD or a response continued L alone until progression. Response assessments performed every 2 cycles. The primary endpoint was overall response rate (ORR) and secondary endpoints were progression-free survival (PFS), time to response, duration of response and overall survival (OS).

Results: Here we present the final analysis of all subjects receiving at least 6 months of protocol therapy. Median age is 56 years; 45 pts (75%) received treatment as 1st line therapy and 15 (25%) as 2nd line; 57% hormone receptor positive and 43% negative; 42% received trastuzumab and 40% received a taxane in either (neo) adjuvant or metastatic setting. After a median of 5.6 months, 7% pts had a complete response, 47% a partial response and 17% had stable disease, the ORR was 53% [95% CI: 41% to 66%]. The median time to response was 7.8 wks [95% CI: 7.4 to 8.1] with a median duration of response of 48.7 wks [95% CI: 31.7 to 57.1]. The median PFS was 39.7 wks [95% CI: 34.1 to 63.9]. Duration of exposure to ab-Pac; 48% received less than 6 cycles, 30% received 6 cycles and 22% received greater than 6 cycles. Table 1 shows the most common G ≥2 treatment-related toxicities. Two fatal adverse events; one pt with a h/o arrhythmia experienced sudden death of presumed cardiac origin and the other subject with h/o COPD, hypertension and uncontrolled diabetes experienced acute renal failure. No G 3/4 elevation in LFTs observed.

Conclusions: L 1000 mg with ab-Pac 100 mg/m2 IV on Day 1, 8, 15, q28 day is feasible with manageable and predictable toxicity. The ORR of 53% compares favorably with other HER2 based combinations in this setting and warrants further exploration

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Cancer Research

DOI

https://doi.org/10.1158/0008-5472.SABCS11-P1-12-10

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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