Abstract P2-12-08: Impact of summation dose intensity product on pathologic response in patients receiving neoadjuvant chemotherapy for early breast cancer
Authors: Thomas M Deutsch, Michelle Kobel, Manuel Feisst, Fabian Riedel, Katharina Smetanay, Carlo Fremd, Laura Michel, Michael Golatta, Joerg Heil, Markus Wallwiener, Andreas Schneeweiss
Journal: Cancer Research (2022)

Abstract Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with beneficial long-term outcome in early breast cancer (EBC). pCR is defined as ypT0/is, ypN0. It is well known that pCR rates depend on tumor subtype. However, the impact of different therapy regimens, dose delays and dose reductions on pCR rates is still unclear. This retrospective study analyzed the therapy dose of patients with pCR and non-pCR after NACT for EBC using referenced and delivered summation dose intensity product (SDIP) and relative dose intensity (RDI) calculations. Methods: SDIP of different therapy regimens were calculated by defining a unit dose intensity (UDI) for each therapy (Hryniuk et al. JCO 1998). The UDI is defined as the dose in mg/m2/week that produces a 30% complete or partial remission rate as a single agent in first-line therapy for metastatic breast cancer. For each regimen, the planned dose intensities (PDI) were divided by the UDI for every single drug. The summation dose intensity (SDI) is the addition of the resulting decimal fractions. Multiplying the SDI by the treatment intervals and number of cycles gives the SDIP. SDIP can be divided into referenced SDIP (rSDIP) and delivered SDIP (dSDIP). RDI is the ratio of dSDIP in comparison to rSDIP. Therapy dose calculations were performed for patients who received NACT for EBC at the National Center for Tumor Diseases (NCT) Heidelberg, Germany, between 01/2015 and 08/2019. Results: 590 patients (median age 51 years) were included, median follow up was 38 months, 225 patients (38.1%) achieved pCR. 65 patients (11.0%) were hormone receptor positive HER2 negative (HR+HER2-), 164 (27.8%) were HR-HER2-, 133 (22.5%) were HR+HER2+, 97 (16.4%) were HR-HER2+. Significant difference between the pCR and non-pCR group was observed for HR-status (p&amp;lt;0.001), HER2-status (p&amp;lt;0.001), tumor grading (p&amp;lt;0.001) and Ki-67 (p&amp;lt;0.001). Age of diagnosis (p=0.611), menopause-status (p=0.769), tumor size (p=0.183) and nodal status (p=0.163) did not significantly vary between patients with pCR versus non-pCR. Patients with pCR had significantly higher rates of anemia II° (p=0.006). No significant difference was seen for anemia ≥III°, neutropenia ≥II°, deviation of liver enzymes ≥II°, nephrotoxicity ≥II°, polyneuropathy ≥II° or the administration of red cell and platelet concentrate as well as the use of Granulocyte-Colony Stimulating Factor (G-CSF). 3 year overall survival (OS), metastasis-free survival (MFS) and recurrence-free survival (RFS) were found to be significantly better in patients with pCR (OS: 98.0% vs. 90.2%, p&amp;lt;0.001; MFS: 94.5% vs. 84.6%, p&amp;lt;0.001; RFS: 97.7% vs. 94.0 %, p=0.029). Patients with pCR had a significantly higher mean rSDIP (69.8 vs. 58.9, p=0.001) and dSDIP (59.5 vs. 49.1, p=0.001). Mean RDI did not significantly vary between pCR and non-pCR (0.853 vs. 0.840, p=0.350). Mean rSDIP and dSDIP significantly vary between the tumor subtypes HR+HER2-, HR-HER2-, HR+HER2+, and HR-HER2+ (rSDIP: 47.4, 54.5, 74.3, 76.7; p&amp;lt;0.001; dSDIP: 39.5, 43.3, 62.0, 67.0; p&amp;lt;0.001). Mean rSDIP and dSDIP did not significantly vary between patients with pCR and non-pCR within the tumor subtypes. Conclusion: Outcomes for NACT are consistent with published data concerning pCR rates. It is notable that the pCR group had significantly higher rSDIP and dSDIP than the non-pCR group whereas RDI and toxicity did not significantly vary between the two groups. rSDIP and dSDIP were mainly depending on the tumor subtype. This data confirms that the tumor subtype has a major impact on pCR rate. Whilst this retrospective analysis must be interpreted with caution, the results show that SDIP is an integral parameter for assessing the efficacy and adequate application of combination therapy and is associated with pCR rate and overall survival. Citation Format: Thomas M Deutsch, Michelle Kobel, Manuel Feisst, Fabian Riedel, Katharina Smetanay, Carlo Fremd, Laura Michel, Michael Golatta, Joerg Heil, Markus Wallwiener, Andreas Schneeweiss. Impact of summation dose intensity product on pathologic response in patients receiving neoadjuvant chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-08.