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).
Authors: Yardley DA , Hart L , Bosserman L , Saleh MN , Waterhouse DM , Richards P , Hagan MK , DeSilvio ML , Mahoney JM , Nagarwala Y 
Published: June 2012

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 &gt; 12 months prior to study entry, LVEF&gt;50%, peripheral neuropathy &lt; 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.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-10.