Real-world outcomes of anthracycline and taxane-based perioperative breast cancer therapy using the Japanese electronic medical record database.

BACKGROUND Relative dose intensity (RDI) of chemotherapy (CT) < 85% significantly decrease therapy efficiency (including overall survival) in early breast cancer (BC) patients (pts). Pathological complete response (pCR) reflects better outcomes and correlates with the RDI of neoadjuvant CT (NAC). Neutropenia is the most common AE leading to RDI drop. Recent studies are demonstrate that G-CSF could switch immunosuppressive tumor microenvironment via neutrophils plasticity. In early BC neutrophils, can mediated antitumor responses by direct killing of tumor cells and by participating in cellular networks that mediate antitumor resistance. Primary G-CSF prophylaxis (PP) with prolonged G-CSF may be an option for optimal therapy results. This multicenter prospective study was designed to evaluate the RDI and treatment outcomes of cytotoxic therapy under PP by empegfilgrastim (E) in pts with high-risk early BC. METHODS High-risk BC pts (n=195) with II-III stages are getting NAC of the following regimens: 4 dose dense doxorubucin/cyclophosphamide with E followed by 12 weekly paclitaxel/carboplatin (4ddAC+E/12P+carbo) for triple negative (TN) pts or 4 dose dense doxorubucin/cyclophosphamide with E followed by 4 dose dense paclitaxel with E (4ddAC+E/4ddP+E) for HR+HER2- pts and 6 docetaxel/carboplatin trastuzumab/pertuzumab (TCHP+E) for HER2+ pts. RDI of therapy course was primary endpoint and presented here for pts who completed the planned regimen. For each agent, the planned and actual dose intensity were calculated by dividing the total cumulative dose by treatment duration in days. RDI was calculated for each single agent in CT regimen and for CT regimen in total. These descriptive analyses were performed for the whole CT regimen. The secondary endpoint: pCR (ypT0/is, ypN0) is also presented here. ClinicalTrials.gov No NCT04905329. RESULTS At the data cut-off (April’2022) 111 pts with BC (HER2+ (n=56); HR+ HER2- (n=17); TN (n=38)) underwent ≥ 1 cycle of NAC with E. The planned CT course completed in 67 (60%) BC pts. RDI≥85% were fixed in 56 (84%) pts: 93% RDI for 4ddAC+E/4ddP+E regimen; 90,3% RDI for 6TCHP+E; 94,1% RDI for 4ddAC+E/12P+carbo. Preliminary, in HER2+ BC pts pCR rate exceeds KRISTINE trial data despite a more enriched pts’ population with poor prognosis (36% pts with IIIB - III C and 65% pts with IIA-IIIA stages per TNM v.8): 93,3% (15 pts HR-) and 70,4% (34 pts HR+). In TNBC pts pCR rate is 56% (9 pts) according to historical control. In HR+ HER2- BC – pCR rate is 20% (10/17 pts under surgery). Neutropenia as a reason of RDI drop was in 1 (0,9%) case in HER2+BC pt. The mature data are awaited. CONCLUSION PP with E allows to maintain RDI efficiently and safely in high-risk recurrence pts populations. High pCR rate under E in HER2+ BC pts focused on further confirmation with translational research. KEY WORDS: empegfilgrastim, neutropenia, pCR, dose intensity, G-CSF, breast carcinoma, neoadjuvant therapy Citation Format: Irina Sorokina, Inna Ganshina, Tansuly Ibragimova, Irina Bondareva, Lyudmila Zhukova. Defendor Special: Primary empegfilgrastim prophylaxis (prolonged G-CSF) for optimal treatment outcomes in high risk early breast cancer cohort. The interim analysis. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-07-23.

Introduction: African American (AA) women are less likely to receive recommended standard treatment or discontinue treatment early for their breast cancer in comparison to white women. Dose reductions and delays during breast cancer chemotherapy can negatively affect survival. The purpose of this study was to examine racial differences in chemotherapy dose modifications among early stage breast cancer patients. We also explored the role of neutropenia in explaining these differences. Methods: Patients were selected from the Breast Cancer Treatment Disparity Study that is composed of AA and white women from New Jersey who were diagnosed with stage I, II, and T3N1M0 breast cancer between 2005-2010, with no prior history of cancer, and age ≤ 85 years. Patients who received chemotherapy as part of their breast cancer treatment were included. Detailed data on chemotherapy administration was abstracted from patient medical records. Chemotherapy dose delivered was measured using relative dose intensity (RDI), defined as the amount of drug delivered per unit time expressed as a fraction of expected dose intensity of a standard regimen. The National Cancer Comprehensive Network Guidelines were used for reference (expected) values of chemotherapy dose and schedule. RDI captures modifications resulting from both delays in administration or reduction in dose and it was computed for the entire course of therapy as well as for each cycle delivered. Racial differences in the mean RDI delivered (per subject and per cycle) and risk of >15% reduction in RDI (per subject) were examined using repeated measures linear and binomial regression models, respectively. The models were adjusted for white blood cell (WBC) level during chemotherapy. Results: The study included 143 AA and 145 white patients (with a total of 2063 chemotherapy cycles). The majority of patients received adjuvant chemotherapy (white= 93.1%, AA= 91.6%) and the remaining received neoadjuvant chemotherapy (white= 6.9%, AA= 8.4%) with no differences by race. Commonly administered regimens were dose-dense doxorubicin/cyclophosphamide followed by paclitaxel every two weeks (AA= 25.2%, white= 32.4%), docetaxel/cyclophosphamide every three weeks (AA= 23.1%, white= 17.2%), doxorubicin/cyclophosphamide every three weeks (AA= 11.9%, white= 12.4%), and doxorubicin/cyclophosphamide followed by weekly paclitaxel (AA= 9.8%, white= 13.1%). Receipt of anthracycline-based regimen was similar between AAs and whites (67.1% and 69.7%, respectively), as was addition of taxanes to anthracycline-based regimen (AA= 82.3%, white= 80.2%). A higher proportion of AA patients (10.5%) did not complete the recommended number of cycles in comparison to whites (5.5%), though the difference was not statistically significant (p= 0.120). Mean RDI per subject was 94.4% for AAs and 100.0% for whites (difference= −5.62%, p= 0.005). After adjusting for WBC level during chemotherapy, the mean RDI difference was −5.29% (p= 0.009). When RDI per cycle was examined, the mean unadjusted and adjusted RDI difference between AAs and whites were −8.27% (p< 0.001) and −7.92% (p< 0.001), respectively. The proportion of patients with >15% reduction in RDI was more than twice among AAs than whites (21.7% versus 8.3%, p=0.001). The unadjusted risk of >15% reduction in RDI was 2.62 (95% CI: 1.40, 4.89) in AA women as compared to white women; and was 2.50 (95% CI: 1.33, 4.70) after adjusting for WBC level. Conclusions: We found that AA breast cancer patients were significantly more likely to receive a reduced dose of chemotherapy as compared to white patients. WBC levels during the course of chemotherapy did not explain the racial disparity in chemotherapy dose reduction. The reasons for dose reduction in AA breast cancer patients merit investigation. This abstract was also presented as Poster A91. Citation Format: Sheenu A. Chandwani, Kim M. Hirshfield, Adana A. Llanos, Elisa V. Bandera, Yong Lin, George G. Rhoads, Kitaw Demissie. Chemotherapy modification by race in early breast cancer treatment. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr PR08.

Background Paclitaxel (PTX) is a standard treatment for metastatic breast cancer (MBC) and it is often used as adjuvant and neoadjuvant chemotherapy for patients with early-stage disease. Nanoparticle albumin-bound (Nab)-PTX was also effective in patients with metastatic and early-stage. A comparison of weekly and triweekly nab-PTX regimens suggested that weekly nab-PTX resulted in superior progression-free survival. However, the optimal dose and schedule of weekly nab-PTX have not been determined. The efficacy and tolerability of epirubicin/cyclophosphamide (EC) followed by weekly nab-PTX (125 mg/m2) ± trastuzumab in node-positive breast cancer was determined in our previous trial. A high pathologic complete response (pCR) rate was obtained in HER2-positive patients. However, because nab-PTX administration was frequently postponed and discontinued, the optimal dose needs to be determined. In the previous trial, the median relative dose intensity of nab-PTX was 80% among patients with pCR. Therefore the dose of nab-PTX was reduced by 20% in this newly designed trial. Trial design This phase II trial aimed to evaluate the efficacy and toxicity of neoadjuvant EC followed by weekly nab-PTX with trastuzumab in patients with HER2-positive breast cancer. Patients will receive 4 cycles of epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks, followed by 4 cycles of nab-PTX (100 mg/m2) on days 1, 8, and 15, over a 28-day cycle. Fifteen cycles of trastuzumab (2 mg/kg, loading dose: 4 mg/kg) will be added to the nab-PTX regimen. Eligibility criteria Surgery and chemotherapy-naïve patients with pathologically confirmed T2-4 N0-3 invasive breast cancer, as diagnosed by core needle biopsy, are included. Eligibility criteria include age 20–70 years, a performance status of 0–2, and adequate organ function. Specific aims The primary endpoint is the pCR rate in the breast and axilla. Secondary endpoints include the breast conservation rate, toxicities, relative dose intensities, feasibility, and overall survival. A pCR is defined as the disappearance of invasive cancer cells, including in the axilla; residual intraductal cancer is acceptable. Statistical methods The sample size was calculated using the Simon method, with a type I error of 5% and a study power of 80%. The expected rate of pCR is 72% with a threshold pCR rate of 45%. The required number of patients was estimated to be 25. Present and target accrual Patient accrual within two medical centers began in May 2014. A final study population of 30 patients is expected (Trial registration: UMIN000013886). Citation Format: Kodera A, Hirano A, Inoue H, Ogura K, Hattori A, Sakaguchi S, Yukawa H, Matsuoka A, Tanaka N, Kamimura M, Jibiki N, Fujibayasi M, Naritaka Y, Shimizu T. A phase II trial of neoadjuvant epirubicin/cyclophosphamide followed by weekly nanoparticle albumin-bound paclitaxel with trastuzumab for HER2-positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-01-03.

Incidence of neutropenia, chemotherapy delivery, and use of colony-stimulating factor in patients with non-Hodgkin lymphoma of different age groups

PurposeThe regimen including concurrent docetaxel, doxorubicin, and cyclophosphamide (TAC) has been categorized as an important risk factor for febrile neutropenia (FN). This comparative study examined the clinical impact of long-acting granulocyte colony-stimulating factor (G-CSF) (pegfilgrastim) during adjuvant TAC chemotherapy in Korean patients with advanced breast cancer.MethodsWe analyzed data from 239 patients who received 6 cycles of adjuvant TAC chemotherapy. We categorized patients into 2 groups according to the use of primary prophylactic pegfilgrastim and compared the incidence and risk of FN, hospital care costs, and survival in the 2 groups.ResultsThe incidence of FN decreased from 54.2% to 21.2% in all patients, after the use of pegfilgrastim. The analysis of a total of 1,432 chemotherapy cycles showed that the incidence of FN decreased from 36.1% to 9.1% after the use of pegfilgrastim. Moreover, the decrease in the incidence of FN with the use of pegfilgrastim resulted in a significant decrease in the mean duration of neutropenia (4.15 to 1.29 days), the risk of hospitalization (99.5% to 29.7%) and the mean total hospital care cost (USD 3,038 to USD 2,347). High relative dose intensity (RDI) in patients treated with pegfilgrastim than in those not treated with pegfilgrastim (99.18% vs. 93.85%) was associated with a better overall survival (p = 0.033).ConclusionsThe use of pegfilgrastim during adjuvant TAC chemotherapy was significantly associated with a decrease in the incidence and risk of FN, hospital care costs, and risk of death compared to the use of adjuvant TAC without primary prophylaxis.

PURPOSEPatients who are HIV-positive and have breast cancer have worse overall survival (OS) compared with patients who are HIV-negative. Pathologic complete response (pCR) and relative dose intensity (RDI) of chemotherapy are associated with survival. We assessed whether pCR and RDI rates were lower for patients who are HIV-positive and received neoadjuvant chemotherapy (NACT).METHODSThis was a prospective cohort analysis of patients initiating NACT in Botswana (February 2017 to September 2019). Primary outcomes were pCR and RDI; secondary outcomes were OS and toxicity. HIV status and zidovudine (ZDV) treatment were stratification factors. Multivariable analysis was used to control for confounding.RESULTSIn total, 26 of 110 enrolled individuals were HIV-positive. In univariable analysis, HIV-positive (odds ratio [OR] = 0.2; P = .048) and RDI < 0.85 (OR = 0.30; P = .025) were associated with pCR. In multivariable analysis, the magnitude of association decreased for HIV-positive (OR = 0.28; P = .11), but RDI < 0.85 remained independently associated with pCR (OR = 0.32; P = .035). Patients who are HIV-positive had significantly lower mean RDI, and those on ZDV had significantly lower RDI. Ninety-one (83%) were stage III with 2-year OS significantly worse for patients who are HIV-positive (58% v 74%). Hazard ratio for all-cause mortality was 2.68 (95% CI, 1.17 to 6.13; P = .028) in patients who are HIV-positive compared with patients who are HIV-negative. Toxicity rates were similar despite patients who are HIV-positive receiving significantly lower dose intensity chemotherapy.CONCLUSIONPatients who are HIV-positive and have breast cancer in Botswana have lower pCR rates and also receive lower dose intensity therapy, which may contribute to worse OS. Patients who are HIV-positive on ZDV-containing regimens received even lower dose intensity of NACT. Administering optimal dose intensity in patients who are HIV-positive remains a challenge, and targeted interventions that address modifiable risk factors are needed to improve therapy delivery and outcomes.

A randomized trial of four cycles of adjuvant AC (adriamycin + cyclophosphamide) ± two cycles of EP (etoposide + cisplatin) in node positive patients with breast cancer

Background: The combination of endocrine therapy with the cyclin-dependent kinases 4/6 inhibitor palbociclib was proven to be effective for the treatment of hormone receptor (HR)-positive/HER2-negative metastatic breast cancer (MBC). Although generally well tolerated, treatment delays and dose reductions are frequently observed with palbociclib, mainly due to severe neutropenia. Predictors of palbociclib-related toxicities are still unknown, as well as the clinical relevance of its relative dose intensity (RDI). Henceforth, this study aimed to identify baseline clinicopathological features associated with a RDI &amp;lt;75% and early dose reduction (within the first 3 months of treatment). Secondarily, we explored the impact of RDI &amp;lt;75% and early dose reduction on progression-free survival. Methods: We reviewed data of 150 consecutive patients with HR-positive/HER2-negative MBC patients treated with palbociclib at two Italian cancer centers from 2017 to 2019. Eligible patients must have received at least 3 cycles of treatment. Those who experienced early suspension due to unacceptable toxicities were still eligible. RDI was calculated as the ratio of actual dose intensity (cumulative administered dose/treatment duration) and planned dose intensity (cumulative planned dose/planned treatment duration). The association of both RDI &amp;lt;75% and early dose reduction with baseline clinicopathological features was assessed using multivariate logistic regression. The following variables were investigated as predictors of dose reduction: de novo vs. recurrent MBC, prior chemotherapy, treatment line, associated endocrine therapy, performance status (PS), weight, renal clearance, hemoglobin level, absolute white blood cell (WBC) count, absolute neutrophils count and absolute platelet count. A ROC analysis was performed to identify the best cut-off for baseline weight in predicting a RDI &amp;lt;75%, while continuous laboratory variables were dichotomized according to clinically relevant cut-offs. Results: Overall, 142 patients were deemed eligible. Of these patients, 98 (69.0%) were treated with palbociclib plus fulvestrant, 44 (31.0%) with palbociclib plus aromatase inhibitors, and 73 (51.4%) in the first-line setting. The median number of administered palbociclib cycles was 8 (range: 1-24) and 61 patients (43.0%) required at least a first-level dose reduction (29 within 3 months). Furthermore, the median time to first dose reduction was 3.22 months, with neutropenia being responsible for 85.24% of first-level dose reductions. In the whole cohort, median RDI was 90.5% (95.1% for patients without dose reduction and 80% for those who had received a dose reduction). Notably, 28 patients (19.7%) experienced a RDI &amp;lt;75%. Through multivariate logistic regression, baseline weight ≤66 kg (OR 3.01, 95% CI: 1.08-8.35, p=0.03) and WBC ≤4.5 × 109/L (OR 3.15, 95% CI: 1.08-9.12, p=0.03) were independently associated with a RDI &amp;lt;75%. Moreover, baseline weight ≤66 kg was also significantly correlated with early dose reduction (OR 2.77, 95% CI: 1.09-7.01, p=0.03). After a median follow-up of 11.76 months, median PFS was 13.99 months. When exploring potential prognostic factors, neither a RDI &amp;lt;75% (HR 1.01, 95% CI: 0.52-1.95, p=0.97) nor a dose reduction within the first 3 months (HR 1.39, 95% CI: 0.67-2.91, p=0.31) did significantly impact PFS. Conclusions: In our analysis, baseline weight and WBC were statistically associated with a RDI &amp;lt;75% in patients with MBC treated with palbociclib. Furthermore, baseline weight was also able to predict an early dose reduction in the study population. Lastly, early dose reduction and RDI &amp;lt;75% did not impact PFS. Although the small sample size and the limited follow-up, our results warrant further investigation in specifically designed trials. Citation Format: Giacomo Pelizzari, Elisa Bertoli, Marco Giavarra, Carla Corvaja, Lorenzo Gerratana, Debora Basile, Michele Bartoletti, Camilla Lisanti, Lucia Bortot, Silvia Buriolla, Mattia Garutti, Debora Avoledo, Marta Bonotto, Lucia Da Ros, Silvia Bolzonello, Mauro Mansutti, Paola Di Nardo, Gianpiero Fasola, Simon Spazzapan, Alessandro M Minisini, Fabio Puglisi. Predictors of relative dose intensity and early dose reduction in patients with metastatic breast cancer treated with palbociclib and endocrine therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-08.

554 Background: In this study we present the updated 10-year results of our randomized trial, assessing the efficacy of 2 cycles of adjuvant etoposide + cisplatin (EP) combination following 4 cycles of standard doxorubicin (Adriamycin) + cyclophosphamide (AC) in premenapausal patients with operable breast cancer and axillary lymph node metastasis. Methods: Premenopausal patients with positive axillary lymph nodes following curative modified radical mastectomy were randomized to either 4 cycles of AC (Adriamycin + Cyclophosphamide) or 4 cycles of AC + 2 cycles of EP (Etoposide + Cisplatin) from May 1992 to May 1996. The doses were as follows: Cyclophosphamide 600 mg/m2 iv, adriamycin 60 mg/m2 iv, Etoposid 100 mg/d x 5 days iv, and cisplatinum 20 mg/m2/d x 5 days iv.Chemotherapy was repeated every 3 weeks. Results: One hundred and sixty five patients were enrolled (82 randomized to AC, 83 to AC + EP). Four patients from AC+EP group and 1 from AC group were excluded because of stage IIIb or IV disease. One h...

Introduction: Use of pegfilgrastim in patients who are at high risk of febrile neutropenia (&amp;gt;18%) results in a 94% reduction in febrile neutropenia. Use of pegfilgrastim is also associated with increased chemotherapy Relative Dose Intensity (RDI) due to fewer dose reductions, delays and discontinuations. Higher RDI has been associated with increased survival. Pegfilgrastim use historically required patients to return the day after chemotherapy. Introduction of the on-body injector (OBI) allows for next day delivery of growth factor without patients having to come back to the clinic. We conducted a study comparing neutropenia rates, dose delays and total cost of care for breast cancer patients receiving chemotherapy with high risk of febrile neutropenia who received (1) no pegfilgrastim, (2) pegfilgrastim via pre-filled syringe (PFS), (3) pegfilgrastim via OBI. Methods: The data utilized for this study originates from the EHRs, practice management systems and CMS claims obtained as part of the Oncology Care Model (OCM) for eight practices supported by Integra Connect Population Health. Using our harmonized data model, DTX, we constructed synthetic chemotherapy episodes of care. Each episode began with an administration of a chemotherapy regimen defined as having a high risk of febrile neutropenia per NCCN. The episode ended the day of the next chemotherapy administration, or after 14 days if no subsequent chemotherapy was given. Each episode was assigned to a cohort, no pegfilgrastim, pegfilgrastim via PFS, or pegfilgrastim via OBI. To evaluate the efficacy and toxicity associated with pegfilgrastim administration, we conducted a matched cohort analysis. Patients were matched based on age, sex, cancer type, number of comorbidities, regimen, chemo start date (within 90 days), whether the administration was the last cycle of chemotherapy, and OCM provider quality metrics. Results: Compared with no pegfilgrastim, PFS episodes had 9.9% less grade IV neutropenia (ANC &amp;lt; 500, p &amp;lt; 0.001) and 5.6% fewer dose delays (p=0.0014, n=916 in each arm). Compared with OBI, PFS episodes had 0.3% less grade IV neutropenia (p=0.47) and 5.3% fewer dose delays (p=0.009, n=2,727 in each arm). Exploratory analysis highlighted differences in physician office and hospital utilization. PFS episodes include more non-chemotherapy office visits than OBI episodes (2.1 vs 1.3, p &amp;lt; 0.001). PFS patients are more likely to have an unplanned office visit (64% vs 23%, p &amp;lt; 0.001) and more likely to receive hydration during an episode (34% vs. 21%, p = 0.021). PFS episodes include less hospital utilization compared with OBI episodes. OBI episodes are 23% more likely to include hospitalization (5.0% vs 6.2%, p=0.031). Discussion: As expected, this observational real-world analysis shows that the use of pegfilgrastim via PFS or OBI is associated with reduced neutropenia rates and reduced dose delays compared with no pegfilgrastim. Comparing PFS with OBI, we see similar neutropenia rates, but PFS shows fewer dose delays and fewer hospitalizations. Exploratory analysis provides some insight into these dose delays and related health care utilization. Our analysis shows that patients returning next day to the cancer center to receive pegfilgrastim frequently receive other services such as labs and hydration. These services lead to fewer dose delays, perhaps because toxicities other than neutropenia are detected earlier in the episode and can be managed in the office. This implies that use of PFS may be used as part of a strategy to shift site of service for management of side effects into the physician office and away from hospitals and emergency departments. Citation Format: Jennifer Webster, Jeffrey Scott, Danielle Wieland, Joseph Donaldson, Ash Malik, Rushir Choksi. Patients receiving pegfilgrastim via prefilled syringe received closer care when compared with on-body injector [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-12.

Relative dose intensity (RDI) has been associated with improved survival in patients with advanced solid tumours. However, there is no evidence regarding RDI in patients under long-term treatment with trabectedin for adult advanced soft tissue sarcoma (STS). Pegfilgrastim use was associated with chemotherapy dose intensity maintenance in patients with various cancers. We retrospectively evaluated the RDI in patients with STS receiving trabectedin. The patients were grouped based on whether trabectedin administration was supported by pegfilgrastim. RDI was obtained for 114 of the 140 included patients. Chemotherapy cycles that included filgrastim were excluded. Patients treated with and without pegfilgrastim had similar RDI rates (77.1% ± 17.6% vs 78.8% ± 16.4%; P = 0.485). Moreover, we found no association between patients receiving ≥4 trabectedin cycles and the use of pegfilgrastim. These results suggested that trabectedin dose delays or reductions should be considered before administering prophylactic pegfilgrastim.

752 Background: The benefits of adjuvant chemotherapy in stage III colon cancer (CC) are well established. However, the consequences of dose delays and modifications are not well established. Relative dose intensity (RDI) and dose scheduling have been shown to have prognostic significance in a number of cancers. We examine the effect of RDI, dose intensity (DI) and dose delays on disease free survival (DFS) and overall survival (OS) in stage III CC. Furthermore, we investigate the role of G-CSF in CC and its role in preserving RDI, and its effect on outcomes. Methods: A retrospective review was conducted for patients with stage III CC seen at a Canadian academic cancer center between 2006 and 2011. Patients who received at least three cycles of FOLFOX or at least two cycles capecitabine were included in the analysis. The RDI and DI were calculated and examined for correlation with DFS and OS. The influence of G-CSF on RDI and DI was also investigated. Results: FOLFOX was used more commonly than capecitabine, 64% vs. 36%. Within the FOLFOX regimen median RDI for oxaliplatin was 76.3%, and 83.5% for 5-FU. Median capecitabine RDI was 73.8%. Median DI were similar at 75.4%, 86.5%, and 69.1%, respectively. 60% of patients receiving FOLFOX got over 80% of their intended dose, while only 29% of patients receiving capecitabine achieved this DI. 3-year DFS was higher when RDI or DI was &gt; 80%, compared to ≤ 80%, for each chemotherapeutic, however the differences did not reach significance. 3-year OS trended towards being higher in patients with an RDI and DI &gt; than 80%, however there were limited events in these groups. Over half of patients on FOLFOX experienced a dose delay, 56.9%, most of whom then received G-CSF, 64.9%. Patients who received G-CSF had a higher DI than those who did not, 74.9% and 87.4% versus 66.5% and 76.8%, for the oxaliplatin and 5-FU components, respectively. 3-year DFS and OS was higher in patients who received G-CSF versus those who did not, 78.3% and 97.5% vs. 69.8% and 91.5%, respectively. Conclusions: In patients with stage III colon cancer an RDI or DI is associated with improved 3-year DFS and OS, although the difference did not reach significance in our review. G-CSF as secondary prophylaxis improves RDI, DI, DFS and OS.

554 Background: In this study we present the updated 10-year results of our randomized trial, assessing the efficacy of 2 cycles of adjuvant etoposide + cisplatin (EP) combination following 4 cycles of standard doxorubicin (Adriamycin) + cyclophosphamide (AC) in premenapausal patients with operable breast cancer and axillary lymph node metastasis. Methods: Premenopausal patients with positive axillary lymph nodes following curative modified radical mastectomy were randomized to either 4 cycles of AC (Adriamycin + Cyclophosphamide) or 4 cycles of AC + 2 cycles of EP (Etoposide + Cisplatin) from May 1992 to May 1996. The doses were as follows: Cyclophosphamide 600 mg/m2 iv, adriamycin 60 mg/m2 iv, Etoposid 100 mg/d x 5 days iv, and cisplatinum 20 mg/m2/d x 5 days iv.Chemotherapy was repeated every 3 weeks. Results: One hundred and sixty five patients were enrolled (82 randomized to AC, 83 to AC + EP). Four patients from AC+EP group and 1 from AC group were excluded because of stage IIIb or IV disease. One hundred and sixty patients were eligible. Patient characteristics including age, number of positive nodes, tumor size and estrogen receptor positivity for both groups were comparable. Median follow-up is 114 months. The 10-year overall survival for the AC+EP group was significantly better when compared to AC only group (58.2% vs 35.6%; p=0.004). Again, the 10 year disease-free survival of the whole group was in favor of AC+EP arm (42.6% vs 28.3%; p=0.070). Conclusions: In conclusion, 2 cycles of EP following 4 cycles of AC have significantly improved the survival of operable breast cancer patients with positive axillary lymph nodes. Detailed results of the trial will be presented at the meeting. No significant financial relationships to disclose.

Background: Neoadjuvant chemotherapy (NACT) is the preferred treatment approach for early-stage triple negative breast cancer (TNBC). Achieving pathologic complete response (pCR) after NACT is associated with improved event-free survival and overall survival in patients with TNBC. Major research efforts have been deployed to identify predictive biomarkers for pCR in TNBC. However, the values of chemotherapy (CT) relative dose intensity (RDI) in predicting pCR remain unclear. Methods: A retrospective analysis was conducted among 96 consecutive patients with early stage TNBC who received NACT between February 2018 and January 2023 at the University of Naples Federico II (Naples, Italy). Patients’ demographics, clinical-pathological features, and type of CT schedules were retrieved from electronic medical records. pCR was defined as the absence of residual invasive or in situ carcinoma in primary tumor and/or lymph nodes, upon chemotherapy administration. RDI was calculated as the ratio of delivered to planned CT dose intensity. RDI was defined as low if &amp;lt; 85% or high if ≥85%, respectively. Univariate and multivariate logistic regression were used to evaluate the association between age, tumor stage, RDI, CT regimen dose type, and pCR. Results: All patients were included in the analysis. Median age at diagnosis was 51 years (range 28-75). Sixty-five (68%) and 31 (32%) patients were diagnosed with stage II and stage III TNBC, respectively. Nineteen (19%) patients received a sequential schedule of anthracycline plus cyclophosphamide (AC) and a taxane (T). Sixty-one (64%) patients received AC followed by concurrent carboplatin-paclitaxel (CaP). Sixteen (17%) patients received the anti-PD1 pembrolizumab in addition to ACCaP chemotherapy backbone (ACCaP-Pem). Fifty-four (56%) patients received a dose-dense AC-based CT. A pCR was achieved in 59 (61%) patients. Interestingly, patients who received a dose-dense AC based neoadjuvant CT had higher chance to achieve a pCR compared with those treated with a non dose-dense AC based CT (70% vs 46%, p = 0.03). Overall, 79 (82%) and 17 (18%) patients received a RDI high and RDI low CT, respectively. No difference in terms of age, body mass index, performance status, tumor stage, type of chemotherapy was observed between the two groups (Table 1). At univariate analysis RDI high (OR 5.18, 95%CI: 1.65-16.31, p=0.005) and dose dense AC-based CT (OR 2.42, 95%CI: 0.18-0.97, p=0.04) were significantly associated with pCR. In a multivariate model including RDI, age, tumor stage, and AC regimen dose type, RDI was the only variable independently associated with pCR (OR 4.60, 95% CI: 1.40-15.06, p = 0.01). Conclusion: A chemotherapy RDI≥ 85% independently predicts pCR in early stage TNBC patients treated with standard NACT. In our cohort, one in five patients received a suboptimal chemotherapy dose intensity affecting at least in part tumor response. Studies with larger TNBC patient populations are warranted to confirm the impact of RDI on pCR and long-term outcomes. Table 1 Citation Format: Roberto Buonaiuto, Giuseppe Neola, Aldo Caltavituro, Paola Trasacco, Federica Pia Mangiacotti, Giovanna Pecoraro, Matteo Lambertini, Erica Pietroluongo, Pietro De Placido, Sabino De Placido, Valeria Forestieri, Mario Giuliano, Grazia Arpino, Carmine De Angelis. The impact of chemotherapy relative dose intensity on pathological complete response in patients with triple negative breast cancer treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-03-07.

Abstract #4111 Introduction&amp;#x2028; In breast cancer (BC), adjuvant chemotherapy has become a standard therapy, resulting in prolonged survival. This goal might be affected by chemotherapy dose reductions and delays that are not uncommon features.&amp;#x2028; The aim of this study was to assess relative dose intensity (RDI) reduction risk factors and define predictive factors.&amp;#x2028; Methods&amp;#x2028; Data regarding BC patients (pts) under anthracycline based-chemotherapy regimens was collected, retrospectively, from two Portuguese centres, between 1998 and 2007, and combined into a database of 783 individuals. Primary G-CSF prophylaxis was not planned. DIEP® (Dose Intensity Evaluation Programme) software was developed to allow calculation of RDI, and includes demographic data, clinical and treatment characteristics, chemotherapy dose modifications and delays, haematological toxicities and patterns of use of G-CSF.&amp;#x2028; Univariate and multivariate analysis was performed to identify factors related to RDI ≤ 90% in these patients. A value of P &amp;lt; 0.05 was considered of statistical significance.&amp;#x2028; Results&amp;#x2028; Pts distribution according to chemotherapy: doxorubicin/cyclophosphamide (A60 C600) – 31,5%, 5-fluorouracil/epirubicin/cyclophosphamide (F500 E100 C500) – 19,2%, 5-fluorouracil/doxorubicin/cyclophosphamide (F500 A50 C500) – 49,3%. A RDI ≤ 90% was frequent across all chemotherapy regimens, but most common in pts receiving FEC (34,7%) and AC (23,5%) regimens.&amp;#x2028; According to univariate analysis, factors related to reduction of RDI were: age ≥ 65 years (P = 0,006), node positive (P = 0,037), chemotherapy regimen (P &amp;lt; 0,001), number of pts with at least one G-CSF administration on secondary prophylaxis (P = 0,015), number of pts with at least one G-CSF administration due to neutropenia or febrile neutropenia (P &amp;lt; 0,001 ) and number of pts with at least one hospitalization due to febrile neutropenia (P &amp;lt; 0.001). In multivariate analysis, independent predictors of RDI ≤ 90% were: AC regimen (P = 0,008), FEC regimen (P = 0,002), age ≥ 65 years old (P = 0,018), node positive (P = 0,016) and at least one hospitalization due to febrile neutropenia (P &amp;lt; 0,001).&amp;#x2028; Conclusion&amp;#x2028; A considerable number of our BC pts, submitted to anthracycline based-chemotherapy, continue to experience RDI reductions. Most affected pts were more than 65 years old, or under FEC or AC regimens, or had node positive tumors. This data might help to identify a subgroup of BC pts that benefit from primary prophylaxis with G-CSF. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4111.