FidoCure® at VCS Mid-Year 2022: Lapatinib to treat grade II and III pulmonary carcinomas carrying ERBB2 V659E mutation: preliminary data

FidoCure® at VCS Mid-Year 2022: Lapatinib to treat grade II and III pulmonary carcinomas carrying ERBB2 V659E mutation: preliminary data

FidoCure® Data at VCS Mid-Year Abstract Presentation Review

Rodrigues L, Girimonte D, Harvey G, Lambert L, Miller A, Hull A, Lewis B, Lopes C, Post G. Lapatinib to treat grade II and III pulmonary carcinomas carrying ERBB2 V659E mutation: preliminary data. In: Veterinary Cancer Society Mid- Year Conference: April 9-12, 2022; Puerto Vallarta, Mexico.

In a nutshell

  • During the Mid-Year Conference of the Veterinary Cancer Society held in Puerto Vallarta in April 2022, FidoCure® researchers presented data on the efficacy of lapatinib as adjuvant therapy for dogs with high grade (grade II and III) primary pulmonary carcinoma after tumor excision.
  • Only tumors carrying the ERBB2 V659E  mutation were evaluated in this analysis.  This hotspot mutation is localized in the transmembrane domain leading to the activation of MAPK/ERK and PI3K/AKT pathways, resulting in proliferation and survival of cancer cells.
  • Treatment, outcomes and survival time of 13 dogs included in this study were evaluated.

The bottom line: Dogs in this dataset treated with lapatinib alone or in association with traditional chemotherapy lived longer compared to standard care.

Background

Pulmonary carcinomas are the most frequent lung tumors in dogs and originate from the epithelium of the airways or alveolar parenchyma1. This tumor usually affects older dogs (those with an average age of 11 years) with no apparent sex predisposition. Dogs living in urban areas and exposed to second-hand smoke have been associated with anthracosis and may have an increased risk for tumor development. Canine pulmonary carcinomas are often located in right lobes with preference for the caudal lung, which is also a common location for tumor development in human nonsmokers.

Almost 30% of affected animals are diagnosed, by chance, during routine health checkups. Some clinical signs can be observed, especially in animals with tumors larger than 3 centimeters (cm), such as coughing, dyspnea, lethargy, hyporexia, weight loss and hemoptysis 1,5,9,12–14. In addition, some paraneoplastic syndromes, which are systemic manifestations indirectly caused by tumors (such as hypertrophic osteopathy and non-regenerative anemia associated with neutrophilic leukocytosis), can be observed to affect dogs with pulmonary carcinoma.

Standard treatment includes surgery as a first choice for most primary pulmonary carcinomas, with either partial or complete lung lobectomies being recommended based upon tumor location. Systemic chemotherapy approaches are limited in their utility in affected dogs, as the effectiveness of this therapy is still not detectable.

ERBB2 V659E  is a hotspot mutation that constantly activates pro-survival ERBB2 signaling. A similar mutation is also seen in humans. In both species, it constitutively activates downstream signaling pathways through AKT and is sensitive to lapatinib. Lapatinib, a small molecule tyrosine kinase inhibitor of both EGFR and ERBB2 receptors, inhibits phosphorylation and cell growth.

Results

The average weight and age of studied dogs were 25.26 Kg (12.2 - 38.9 Kg) and 11.3 years (7 - 14 years). Thirteen dogs underwent surgery for tumor removal: four had complete excision, six narrow excision, two incomplete excision and for one dog the margin was not informed in the histology report. Tumor margins were evaluated according to McNiel et al., 1997. Lymph node involvement was not evaluated in all cases and for this reason, was not evaluated in this study. Twelve tumors were measured and classified as stage TI (< 3cm) (3/12), TII (3-5 cm) (1/12), TIII (5-7 cm) (3/12) and TIV (>7 cm) (5/12). Tumors were histologically classified as pulmonary carcinoma (3/13), bronchoalveolar carcinoma (4/13) and papillary carcinoma (6/13). Twelve dogs were diagnosed with pulmonary carcinoma grade II and one dog was diagnosed with grade III.

In addition to surgery, one dog had radiation and chemotherapy before lapatinib, and five dogs received either carboplatin or vinblastine before starting lapatinib. One dog started lapatinib when metastasis was diagnosed.

Objective response was observed in the treated dogs. Those dogs treated with traditional chemotherapy and lapatinib had a median survival time (MST) of 372 days (84 to 423 days). One dog had radiation therapy, chemotherapy and lapatinib with a MST of 380 days, and nine dogs received lapatinib only with a MST of 380 days (141 to 567 days).  The MST of all dogs from diagnosis to death or last follow up was 380 days, and MST from treatment with lapatinib to death was 274 days. Four dogs are still alive and follow-up information is still being collected.

Conclusions

  • This is the first time lapatinib has been evaluated as a treatment for pulmonary carcinoma in dogs with ERBB2 V659E mutation.
  • These findings demonstrate the feasibility of creating a clinical genomic database derived from routine clinical experience and provide support for further research and discovery evaluating this approach in oncology.
  • Lapatinib can be used as adjuvant therapy to increase survival time of dogs with pulmonary carcinoma.

We look forward to additional research based on these dogs and additional cases submitted to us. Continuously enrolling dogs with pulmonary carcinoma, enables FidoCure® to increase survival times and to  expand scientific knowledge on canine precision medicine through our outcomes collection program. A Win-Win for dogs and for science.

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