Taxane-based Chemotherapy Regimens Research Articles

White blood cell kinetics in patients with gynecologic cancer receiving mecapegfilgrastim prophylaxis: A multicenter real-world study.

e17502 Background: Some studies have indicated that using granulocyte-colony stimulating factor (G-CSF) following chemotherapy in patients with solid tumors may increase the risk of excessive white blood cell (WBC) elevation. In this real-world study, we aimed to assess the changes in WBC counts after prophylactic administration of 6 mg mecapegfilgrastim (a long-acting G-CSF) in multiple chemotherapy cycles among Chinese gynecological cancer patients, with a particular focus on those with low body weight (≤50 kg). Methods: A multicenter prospective cohort study was conducted involving gynecological cancer patients who received at least two consecutive chemotherapy cycles with mecapegfilgrastim 6 mg (administered 24 hours post-chemotherapy) between October 2019 and November 2021. Absolute WBC and absolute neutrophil counts (ANC) were recorded at baseline and on the 7th and 14th days of each cycle. Results: A total of 256 gynecological cancer patients completing 2-4 treatment cycles, including 86 with cervical cancer, 136 with ovarian cancer, and 34 with endometrial cancer, were analyzed. Of them, 58 had a pre-chemotherapy body weight of ≤50 kg, and 198 had a body weight of >50 kg. The majority of patients received taxane-based chemotherapy regimens with a cycle duration of ≥14 days. For day 7 post-chemotherapy WBC counts, data were collected from 535 cycles, including 125 cycles in the ≤50 kg group and 410 cycles in the >50 kg group. Elevated WBC counts (>10.0×10^9/L) were observed in 56 cycles (44.8%) in the ≤50 kg group and 177 cycles (43.2%) in the >50 kg group. On day 14 post-chemotherapy, data from 505 cycles, comprising 115 cycles in the ≤50 kg group and 390 cycles in the >50 kg group, indicated elevated WBC counts in 27 cycles (23.5%) in the ≤50 kg group and 63 cycles (16.2%) in the >50 kg group. In the ≤50 kg group, 3 cases (5.2%) experienced an ANC <0.5×10^9 /L, with no febrile neutropenia observed. In the >50 kg group, 11 cases (5.6%) experienced an ANC <0.5×10^9 /L, with 1 patient (0.51%) experiencing febrile neutropenia. Conclusions: In patients with low body weight (≤50 kg), the administration of 6 mg mecapegfilgrastim effectively stabilizes WBC elevation, exhibiting a favorable safety and efficacy profile. This regimen ensures the timely and appropriate progression of patients to subsequent cycles of chemotherapy. WBC counts in patients. [Table: see text]

Abstract GS02-02: Are nodal ITCs after neoadjuvant chemotherapy an indication for axillary dissection? The OPBC05/EUBREAST-14R/ICARO study

Abstract GS02-02: Are nodal ITCs after neoadjuvant chemotherapy an indication for axillary dissection? The OPBC05/EUBREAST-14R/ICARO study

Real-world data of HER2-negative early breast cancer patients treated with anthracycline and/or taxane regimens in Japan

BackgroundAnthracycline- and taxane-based chemotherapy regimens are established treatments for human epidermal growth factor receptor (HER)2-negative early-stage breast cancer with high risk of recurrence. This study examined the prevalence of these chemotherapy regimens as perioperative therapy, the patterns of retreatment, and factors influencing prescription choices in Japan.MethodsThis observational cohort study focused on high-risk early-stage breast cancer patients not undergoing anti-HER2 therapy, utilizing data from a hospital-based claims database in Japan spanning from April 2008 to September 2021.ResultsOf 42,636 high-risk patients who underwent breast cancer surgery, 32,133 (75.4%) were categorized as having luminal-type (received endocrine therapy) and 10,503 (24.6%) as having triple-negative cancer (not receiving any endocrine therapies). Most patients (98.7%) with luminal-type breast cancer received perioperative therapy, and 40.3% of those received anthracycline/taxane. In the triple-negative group, 57.0% of all patients received perioperative therapy and of those, 93.4% received anthracycline/taxane. Being over 40 years old, having an early stage (clinical stage ≤ II), and receiving treatment in non-specialized facilities were associated with less use of anthracycline/taxane in the luminal-type group. For the triple-negative group, associated factors with less use of anthracycline/taxane included being over 60 years old, treatment in small hospital (capacity < 200 beds), and treatment in non-specialized facilities.ConclusionsApproximately half the patients in both the luminal-type and triple-negative groups were prescribed anthracycline and/or taxane for perioperative chemotherapy. The choice was associated with patient age, cancer stage, and the scale and specialization of the treatment facilities. This study sheds light on the current state of breast cancer treatment practices in Japan.

Genomic Correlates of Prostate-Specific Membrane Antigen Expression and Response to 177Lu-PSMA-617: A Retrospective Multicenter Cohort Study.

While 177Lu-PSMA-617 (LuPSMA) is an effective therapy for many patients with metastatic castration-resistant prostate cancer (mCRPC), biomarkers associated with outcomes are not well defined. We hypothesized that prostate cancer mutational profile may associate with clinical activity of LuPSMA. We devised a study to evaluate associations between mCRPC mutational profile with LuPSMA clinical outcomes. This was a multicenter retrospective analysis of patients with mCRPC with next-generation sequencing (NGS) who received LuPSMA. PSA50 response (ie, ≥50% decline in prostate-specific antigen [PSA]) rate, PSA progression free survival (PSA PFS), and overall survival (OS) were compared between genetically defined subgroups. One hundred twenty-six patients with NGS results who received at least one cycle of LuPSMA were identified. The median age was 73 (IQR, 68-78) years, 124 (98.4%) received ≥1 prior androgen receptor-signaling inhibitor, and 121 (96%) received ≥1 taxane-based chemotherapy regimen. Fifty-eight (46%) patients with a DNA damage repair gene mutation (DNA damage response group) and 59 (46.8%) with a mutation in TP53, RB1, or PTEN tumor suppressor genes (TSG group) were identified. After adjusting for relevant confounders, the presence of ≥1 TSG mutation was associated with shorter PSA PFS (hazard ratio [HR], 1.93 [95% CI, 1.05 to 3.54]; P = .034) and OS (HR, 2.65 [95% CI, 1.15 to 6.11]; P = .023). There was improved OS favoring the DNA damage response group (HR, 0.37 [95% CI, 0.14 to 0.97]; P = .044) on multivariable analysis. Univariate analysis of patients with ATM mutations had significantly higher rates of PSA50 response, PSA PFS, and OS. Outcomes on LuPSMA varied on the basis of mutational profile. Prospective studies to define the clinical activity of LuPSMA in predefined genomic subgroups are justified.

71 (PB-071) Poster - Zoledronic acid in combination with standard neoadjuvant anthracycline and taxane-based chemotherapy regimen in patients with early and locally advanced triple-negative breast cancer – A single-arm open-label phase II study (ZACT)

71 (PB-071) Poster - Zoledronic acid in combination with standard neoadjuvant anthracycline and taxane-based chemotherapy regimen in patients with early and locally advanced triple-negative breast cancer – A single-arm open-label phase II study (ZACT)

Relative dose intensity of taxane-based chemotherapy in breast cancer patients in a tertiary hospital.

Breast cancer (BC) is the most diagnosed tumor among women worldwide. The aim of this study was to investigate the incidence and causes of low relative dose intensity (RDI) < 85% for taxane-based chemotherapy regimens used in the treatment of BC in Sultan Qaboos University Hospital (SQUH). This was a retrospective study that included 303 BC patients, treated with taxane-based chemotherapy protocols at SQUH. RDI was calculated for each chemotherapy regimen and causes and predictors of low RDI < 85% were identified. Prophylactic and therapeutic supportive measures for certain toxicities were studied. 50.8% of the patients had neoadjuvant chemotherapy, 38% had adjuvant chemotherapy, and 11.2% of patients were given palliative treatment. AC-T and AC-THP were the most used regimens (40.3% and 17.2%). Mean RDI of used taxane-based chemotherapy regimens was 93.4%. Dose delays, dose reductions, and treatment discontinuation occurred in 36.6%, 14.8%, and 11.5%, respectively. Thirty-eight patients (12.5%) had low RDI < 85% which was reduced to 9.9% after the use of an alternative taxane. Age and chemotherapy intent were significant risk factors. 83.8% received primary granulocyte colony stimulating factor. An optimal RDI greater than 85% was achieved in most cases. Furthermore, prophylactic and therapeutic supportive measures were widely used.

Major cardiovascular adverse events in older adults with early-stage triple-negative breast cancer treated with adjuvant taxane + anthracycline versus taxane-based chemotherapy regimens: A SEER-medicare study

BackgroundTriple-negative breast cancer (TNBC) is more aggressive as compared to other subtypes of breast cancer with characteristic metastatic patterns and a poor prognosis. The standard of care for early-stage TNBC is historically anthracycline and taxane-based chemotherapy (ATAX). Despite the effectiveness of this regimen, anthracyclines carry a small but important risk of cardiotoxicity, which is specifically a concern in the older population. This study evaluates major adverse cardiovascular events (MACE) in older women with TNBC treated with ATAX compared to taxane-based chemotherapy (TAX). MethodsUsing the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified women aged 66 and older with TNBC diagnosed between 2010 and 2015 (N = 2215). We compared patient and clinical characteristics according to adjuvant chemotherapy regimen (chemotherapy versus no chemotherapy and ATAX versus TAX). Logistic regression was performed to estimate the odds ratios (OR) and 95% confidence intervals (CIs), Kaplan-Meier survival curves were generated to estimate three-year overall survival (OS) and cancer specific survival (CSS). Cox proportional hazards models were used to analyze OS and CSS while controlling for patient and tumor characteristics. MACE was defined as acute myocardial infarction, heart failure, potentially fatal arrhythmia, and cerebral vascular incidence. Few patients experienced a cardiac death and therefore this was excluded in the analysis. ResultsOf the 2215 patients in our cohort, most patients (n = 1334; 60.26%) received TAX compared to ATAX (n = 881; 39.78%). Patients who received ATAX were not statistically significantly more likely than those who received TAX to experience acute myocardial infarction, cerebral vascular accident (CVA), or potentially fatal arrhythmia when controlling for traditional risk factors. Among patients who experienced MACE, there was no difference in OS or CSS in patients who received TAX vs ATAX. Patients who received ATAX were less likely to develop heart failure than those who received TAX (OR 0.63, 95% CI [0.45–0.88], p < 0.01). Patients who developed MACE and who were > 76 years old had worse OS compared to those who experienced MACE and were age 66–75 years old (HR 1.67, 95% CI [1.07–2.62], p = 0.02). ConclusionAmong older women with TNBC, receipt of adjuvant chemotherapy with ATAX was not associated with increased risk of major adverse cardiac events. For those who experienced a cardiac event, there was no difference in survival amongst those who received TAX vs ATAX. Other factors including additional chemotherapy toxicities should be investigated as a potential etiology for the inferior OS previously observed with ATAX vs TAX in older women with node negative or 1–3 positive lymph nodes.

Neoadjuvant Talazoparib in Patients With Germline BRCA1/2 Mutation-Positive, Early-Stage Triple-Negative Breast Cancer: Results of a Phase II Study.

The undetermined efficacy of the current standard-of-care neoadjuvant treatment, anthracycline/platinum-based chemotherapy, in patients with early-stage triple-negative breast cancer (TNBC) and germline BRCA mutations emphasizes the need for biomarker-targeted treatment, such as poly(ADP-ribose) polymerase inhibitors, in this setting. This phase II, single-arm, open-label study evaluated the efficacy and safety of neoadjuvant talazoparib in patients with germline BRCA1/2-mutated early-stage TNBC. Patients with germline BRCA1/2-mutated early-stage TNBC received talazoparib 1 mg once daily for 24 weeks (0.75 mg for moderate renal impairment) followed by surgery. The primary endpoint was pathologic complete response (pCR) by independent central review (ICR). Secondary endpoints included residual cancer burden (RCB) by ICR. Safety and tolerability of talazoparib and patient-reported outcomes were assessed. Of 61 patients, 48 received ≥80% talazoparib doses, underwent surgery, and were assessed for pCR or progressed before pCR assessment and considered nonresponders. pCR rate was 45.8% (95% confidence interval [CI], 32.0%-60.6%) and 49.2% (95% CI, 36.7%-61.6%) in the evaluable and intent-to-treat (ITT) population, respectively. RCB 0/I rate was 45.8% (95% CI, 29.4%-63.2%) and 50.8% (95% CI, 35.5%-66.0%) in the evaluable and ITT population, respectively. Treatment-related adverse events (TRAE) were reported in 58 (95.1%) patients. Most common grade 3 and 4 TRAEs were anemia (39.3%) and neutropenia (9.8%). There was no clinically meaningful detriment in quality of life. No deaths occurred during the reporting period; 2 deaths due to progressive disease occurred during long-term follow-up (>400 days after first dose). Neoadjuvant talazoparib monotherapy was active despite pCR rates not meeting the prespecified threshold; these rates were comparable to those observed with combination anthracycline- and taxane-based chemotherapy regimens. Talazoparib was generally well tolerated. NCT03499353.

Early taxane-induced neurotoxicity and quality of life in patients with breast cancer: A single center, retrospective study.

e12533 Background: Taxane administration in breast cancer patients relates to significant chemotherapy-induced peripheral neuropathy (CIPN). In our four years retrospective observational study, we aimed to evaluate early onset of neuropathy and its influence in patients’ quality of life, assessed through certified questionnaires. Methods: We retrospectively collected data from stage I-III breast cancer patients treated with taxane-based therapy between 2018 and 2022 at the Medical Oncology Unit of the University Hospital of Cagliari. We included 300 patients. The median age was 57 years (range, 32-85). All patients followed a schedule of PCT 80mg/m2 ± 30 weekly; they received up to a maximal cumulative dose of PCT 960 ± 30 mg/m2. Peripheral neuropathy was evaluated by the NCI-CTC scale (national cancer institute, common toxicity criteria for adverse events) at every drug administration. Patient-reported EORTC QLQ-CIPN20 and FACT-TAXANE questionnaires were collected at baseline, at 4 and 12 weeks of treatment. We used the Kruskal-Wallis test for the association between the neurotoxicity grade and quality of life. Difference in the questionnaire score at the different timing was assessed by ANOVA test for repeated measures. To assess the strength of the correlation between the different quality-of-life questionnaires, we used Spearmann's Rho test. Statistical analysis was performed with the MedCalc Statistical Software Version 14.10.2. Results: Our analysis revealed that neurotoxicity influences the quality of life assessed with the QLQ at cycle IV (p = 0.000001) and cycle XII (p = 0.008). With just a cumulative dose of 320 mg/m2 (cycle IV), patients without neurotoxicity achieved a median value of 32 in the QLQ, compared to a median value of 34 in patients with grade 1 toxicity and 43 in the group of patients with grade 2 toxicity. Similarly, at cycle XII and with cumulative dose of 960 mg/m2, patients without neurotoxicity achieved a median value of 27 at the QLQ, compared to a median value of 33 in patients with grade 1 toxicity and 34 in the group of patients with grade 2 toxicity. The ANOVA test showed a significant increase (worsening) in the CIPN20 questionnaire at 4 and 12 weeks versus baseline (p &lt; 0.001 for both). The score remained significantly higher in comparison to baseline also at the evaluation at 3 (p &lt; 0.001), 6 (p &lt; 0.001) and 12 months (p &lt; 0.0001). Similarly, the FACT-TAXANE questionnaire showed a significant worsening at 4 (p &lt; 0.001) and 12 (p &lt; 0.001) weeks in comparison to baseline. Conclusions: The majority of women who received a taxane based chemotherapy regimen for breast cancer reported neurotoxicity. In our study, the use of specific questionnaires (EORTC QLQ-CIPN20 and FACT-TAXANE) allowed to identify early neurotoxicity onset and its correlation to quality of life, yet at an initial phase of treatment (after a cumulative dose of 320 mg/m2 of paclitaxel at IV cycle).

Postoperative complications after esophagectomy for cancer, neoadjuvant chemoradiotherapy compared to neoadjuvant chemotherapy: A single institutional cohort study

BackgroundComplications after esophagectomy are common and the possible increase in postoperative complications associated with neoadjuvant chemoradiotherapy is of concern. The aim of our study was to analyze if the addition of radiotherapy to neoadjuvant chemotherapy increases the incidence and severity of postoperative complications, including evaluation of the relation between radiation doses to the heart and lungs and postoperative complications. MethodsThe study was based on an institutional surgical database for esophageal cancer. The study period was October 2008 to March 2020. Patients treated with neoadjuvant chemoradiotherapy were compared to patients treated with neoadjuvant chemotherapy and dose/volume parameters for the lungs and heart considered. The primary outcome was 30-day postoperative complications. ResultsDuring the study period, 274 patients underwent surgery for esophageal cancer, 93 patients after neoadjuvant chemotherapy and 181 patients after neoadjuvant chemoradiotherapy. The median prescribed radiation dose to the planning target volume was 41.4 Gy, the median of the mean lung dose was 6.2 Gy, and the median of the mean heart dose was 20.3 Gy. The addition of radiotherapy to neoadjuvant chemotherapy did not increase the incidence of postoperative complications. Neither were radiation doses to the lungs and heart associated with postoperative complications. Taxane-based chemotherapy regimens were however associated with an increased incidence of postoperative complications. ConclusionsIn our cohort, the addition of neoadjuvant radiotherapy to chemotherapy was not associated with postoperative complications. However, taxane-based chemotherapy regimens, with or without concomitant radiotherapy, were associated with postoperative complications.

Abstract GS4-02: Oncological Outcomes Following Omission of Axillary Lymph Node Dissection in Node Positive Patients Downstaging To Node Negative with Neoadjuvant Chemotherapy: the OPBC-04/EUBREAST-06/OMA study

Abstract Background: Data on the oncologic safety of omission of axillary lymph node dissection (ALND) in node positive (N+) patients who downstage to ypN0 with neoadjuvant chemotherapy (NAC) is sparse. Additionally, there is no consensus on which axillary staging procedure should be used in this setting, sentinel lymph node biopsy (SLNB) alone or in combination with localization and retrieval of the clipped positive node, also known as targeted axillary dissection (TAD). Whether the reduction in the false negative rate observed with TAD translates into a significant reduction in the rate of axillary recurrence is unknown. We sought to evaluate oncologic outcomes after omission of ALND in a large, real-world cohort of breast cancer (BC) patients and to compare rates of axillary recurrence after SLNB with dual tracer mapping vs. TAD. Methods: Data were collected from 19 centers in the Oncoplastic Breast Consortium (OPBC) and EUBREAST networks. Patients with T1-4 biopsy-proven N1-3 BC who underwent NAC followed by axillary staging with either SLNB with dual tracer mapping or TAD and who were pathologically node negative (ypN0) were included. ypN0 was defined as the absence of any tumor or isolated tumor cells. Competing risk analysis was performed to assess the cumulative incidence rates of axillary recurrence, locoregional recurrence, and any invasive (locoregional or distant) recurrence. Two-year cumulative incidence rates were compared between TAD and SLNB using the Gray’s test. Type I error rate was set to 0.05 (α). Results: We included 785 patients (565 treated with SLNB and 220 with TAD) treated with NAC followed by surgery from 01/2014-12/2020. Median patient age was 50 years. The majority (57%) of patients had clinical T2 tumors, and 95% had N1 disease. Most (55%) were HER2+, and 21% were triple negative. Most patients (81%) received anthracycline and taxane-based chemotherapy regimens, but NAC regimens differed between patients treated with TAD and those treated with SLNB (Table 1). All patients with HER2+ tumors received anti HER2 therapy. Nodal radiotherapy was administered to 76% of patients, and was more common in patients who underwent TAD (82% TAD vs 74% SLNB, p=0.017). Breast pathologic complete response (ypT0/is) was more frequent among those patients that had TAD (80% TAD vs. 66% SLNB, p&amp;lt; 0.001). TAD localization was with wire in 46%, radioactive seed in 40%, ultrasound in 5%, tattoo in 2%, and with a combination of these techniques in 7%. The clipped node was successfully retrieved in 94% of TAD cases. The median number of lymph nodes removed was lower in the TAD group compared to the SLNB group [3 (IQR 3-5) vs 4 IQR 3-5), p&amp;lt; 0.001], as was the median number of sentinel lymph nodes [3 (IQR 2-4) vs 4 IQR 3-5), p&amp;lt; 0.001] (Table 1). The 5-year rates of any axillary recurrence, locoregional recurrence, and any invasive recurrence in the entire cohort were 1.1% (95%CI 0.39-2.4%), 3.1% (95%CI 1.6-5.3%) and 10% (95%CI 7.6-13%), respectively. The two-year cumulative incidence of axillary recurrence did not differ between patients treated with TAD compared to SLNB (0% vs 0.9%, p=0.19). Conclusion: Early axillary recurrence after omission of ALND in patients who successfully downstage from N+ to ypN0 with NAC is a rare event following both SLNB or TAD, and was not significantly lower in TAD than SLNB. Although longer follow-up is needed to confirm these findings, the main advantage of TAD seems to be a reduction in the number of lymph nodes removed. Overall, these results support omission of ALND in patients who successfully downstage to node negative disease after NAC. Table 1: Clinicopathological Features of the Study Cohort, Stratified by Axillary Staging Technique Citation Format: Giacomo Montagna, Mary Mrdutt, Astrid Botty, Andrea V. Barrio, Varadan Sevilimedu, Judy C. Boughey, Tanya L. Hoskin, Laura H. Rosenberger, E Shelley Hwang, Abigail Ingham, Bärbel Papassotiropoulos, Bich Doan Nguyen-Sträuli, Christian Kurzeder, Danilo Diaz Aybar, Denise Vorburger, Dieter Michael Matlac, Edvin Ostapenko, Fabian Riedel, Florian Fitzal, Francesco Meani, Franziska Fick, Jacqueline Sagasser, Jörg Heil, Konstantin J. Dedes, Laszlo Romics, Maggie Banys-Paluchowski, Maria Del Rosario Cueva Perez, Marcelo Chavez Diaz, Martin Heidinger, Mathias K. Fehr, Mattea Reinisch, Nadia Maggi, Nicola Rocco, Nina Ditsch, Oreste Davide Gentilini, Regis Resende Paulinelli, Sebastian Sole Zarhi, Sherko Küemmel, Simona Bruzas, Simona Di Lascio, Tamara Parissenti, Uwe Güth, Valentina Ovalle, Christoph Tausch, Monica Morrow, Thorsten Kühn, Walter P. Weber. Oncological Outcomes Following Omission of Axillary Lymph Node Dissection in Node Positive Patients Downstaging To Node Negative with Neoadjuvant Chemotherapy: the OPBC-04/EUBREAST-06/OMA study [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 GS4-02.

Clinical outcomes of adjuvant taxane plus anthracycline versus taxane-based chemotherapy regimens in older adults with node-positive, triple-negative breast cancer: A SEER–Medicare study

BackgroundTriple-negative breast cancer (TNBC) is a subtype of breast cancer associated with an aggressive clinical course. Adjuvant chemotherapy reduces the risk of recurrence and improves survival in patients with node-positive TNBC. The benefit of anthracycline plus taxane (ATAX) regimens compared with non-anthracycline-containing, taxane-based regimens (TAX) in older women with node-positive TNBC is not well characterised. MethodsUsing the Surveillance, Epidemiology, and End Results–Medicare database, we identified 1106 women with node-positive TNBC diagnosed at age 66 years and older between 2010 and 2015. We compared patient clinical characteristics according to adjuvant chemotherapy regimen (chemotherapy versus no chemotherapy and ATAX versus TAX). Logistic regression was performed to estimate the odds ratios (OR) and 95% confidence intervals (CIs). Kaplan–Meier survival curves were generated to estimate 3-year overall survival (OS) and cancer-specific survival (CSS). Cox proportional hazard models were used to analyse OS and CSS while controlling for patient and tumour characteristics. ResultsOf the 1106 patients in our cohort, 767 (69.3%) received adjuvant chemotherapy with ATAX (364/767, 47.5%), TAX (297/767, 39%) or other regimens (106/767, 13.8%). Independent predictors of which patients were more likely to receive ATAX versus TAX included more extensive nodal involvement (≥4), age, marital/partner status and non-cardiac comorbidities. There was a statistically significant improvement in 3-year CSS (81.8% versus 71.4%) and OS (70.7% versus 51.3%) with the use of any chemotherapy in our cohort (P < 0.01). Three-year CSS and OS for patients who received ATAX versus TAX were similar at 82.8% versus 83.7% (P = 0.80) and 74.2% versus 72.7% (P = 0.79), respectively. There was a trend towards improved CSS and OS in patients with four or more positive lymph nodes who received ATAX versus TAX (hazard ratio 0.66, 95% CI: 0.36–1.23, P = 0.19 and hazard ratio 0.68, 95% CI: 0.41–1.14, P = 0.14, respectively). ConclusionAmong older women with node-positive TNBC, a majority of patients received adjuvant chemotherapy, which was associated with an improvement in CSS and OS. When compared with TAX chemotherapy, there was a trend towards better outcomes with ATAX for patients with ≥4 nodes.

1368P TALAPRO-1: Talazoparib monotherapy in metastatic castration-resistant prostate cancer (mCRPC) with DNA damage response alterations (DDRm) – Exploration of tumor genetics associated with prolonged benefit

TALAPRO-1 enrolled men with progressive mCRPC, measurable soft-tissue disease, and tumor DDRm involved directly or indirectly in homologous recombination repair (11-gene panel). Enrolled men had received 1–2 taxane-based chemotherapy regimens and progressed on ≥1 novel hormonal therapy. Confirmed objective response rate (primary endpoint; per RECIST 1.1; blinded independent central review [BICR]) was 29.8%. The molecular bases of prolonged clinical benefit with poly(ADP-ribose) polymerase inhibitors are incompletely understood, although limited evidence suggests that patients exhibiting large deletions in BRCA genes may experience extended benefit. Exploratory post hoc biomarker analyses assessed tumor genetics associated with prolonged antitumor benefit in TALAPRO-1. Tumor alterations were assessed using FoundationOne®CDx. Zygosity of tumor alterations was predicted using somatic-germline-zygosity. Prolonged benefit was assessed as radiographic progression-free survival ([rPFS]; RECIST 1.1/PCWG3; BICR) time to event or censoring. Data cutoff was Sept 4, 2020 (primary completion date). Of 104 men in the efficacy population, 16 had rPFS of ≥12 months. Of their 16 tumors, 15 (94%) had BRCA2 alterations, including 10 large structural variants (9 copy number loss, 1 rearrangement) and 5 short variants (SV; 4 homozygous). In contrast, only 6/27 (22%) men with rPFS <2.0 months exhibited BRCA2 alterations (1 rearrangement, 1 non-defined, and 4 SV with 2 homozygous). Of 61 men with rPFS <12 months but ≥2 months, 36 (59%) had BRCA2 alterations (9 copy number loss, 1 rearrangement, 21 SV [11 homozygous], 2 multiple alterations [1 homozygous], and 3 not defined). Conversely, TP53 alterations were less common for men with rPFS ≥12 months vs <2 months (2/16 vs 14/27; P=0.02 Fisher’s exact test, 2-tails), potentially reflecting negative prognosis or a subgroup less sensitive to PARP inhibition. Based on these retrospective, exploratory analyses of TALAPRO-1, men exhibiting prolonged benefit typically exhibited BRCA2 copy number loss or homozygous alterations, and lacked TP53 alterations.

Immunogenicity evaluation of ChAdox1 nCov-19 (AZD1222) vaccine in solid cancer patients in Chulabhorn Hospital

ABSTRACT Introduction Cancer patients are more vulnerable to coronavirus disease 2019 (COVID-19) owing to their compromised immune status. However, data regarding COVID-19 vaccine safety and immune response in cancer patients are scarce. Method This prospective, age- and sex-matched, single-center cohort study included 61 cancer patients and 122 healthy control participants. Seropositivity was defined as anti-S IgG titer >0.8 units/ml. Primary end point was seroconversion rate of immunoglobulin (Ig)G antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein (anti-S IgG) in cancer patients vs. healthy control participants following the second dose of COVID-19 vaccine ChAdOx1 nCoV-19 (AZD1222). Results After the second-dose vaccination, there was no difference in seropositivity rate between groups (57 [93.44%] patients with cancer vs. 121 [99.18%] control participants; geometric mean ratio [GMR]: 0.39; 95%CI: 0.01–10.46; p-value = 0.571). In contrast, after the first-dose vaccination, the seropositivity rate was significantly lower in the cancer patients than in the control participants (50/61 [81.97%] vs. 121/122 [99.18%]; GMR: 0.07; 95%CI: 0.01–0.71; p = 0.025). The median anti-S IgG titer after the first-and second dose vaccination were not significantly different between groups. Female sex was significantly associated with a higher anti-S IgG titer. 5FU- and taxane-based chemotherapy regimens were associated with a lower IgG titer. Side effects of vaccination were tolerable. Conclusions The anti-S IgG seropositivity rate after completing the second vaccine dose did not differ between the cancer patients and control participants. However, the anti-S IgG seropositivity rate after the first-dose vaccination was lower in cancer patients.

Patient-reported Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Harboring DNA Damage Response Alterations Treated with Talazoparib: Results from TALAPRO-1

BackgroundTalazoparib has shown antitumor activity with a manageable safety profile in men with metastatic castration-resistant prostate cancer (mCRPC) and DNA damage response (DDR)/homologous recombination repair (HRR) alterations. ObjectiveTo evaluate patient-reported health-related quality of life (HRQoL) and pain in patients who received talazoparib in the TALAPRO-1 study, with a special interest in patients harboring breast cancer susceptibility gene 1 or 2 (BRCA1/2) mutations. Design, setting, and participantsTALAPRO-1 is a single-arm, phase 2 study in men with mCRPC DDR alterations either directly or indirectly involved in HRR, who previously received one to two taxane-based chemotherapy regimens for advanced prostate cancer and whose mCRPC progressed on one or more novel hormonal agents. Outcome measurements and statistical analysisMen completed the European Quality-of-life Five-dimension Five-level scale (EQ-5D-5L), EQ-5D visual analog scale (VAS), and Brief Pain Inventory—Short Form at predefined time points during the study. The patient-reported outcome (PRO) population included men who completed a baseline and one or more postbaseline assessments before study end. Longitudinal mixed-effect models assuming an unstructured covariance matrix were used to estimate the mean (95% confidence interval [CI]) change from baseline for pain and general health status measurements among all patients and patients with BRCA1/2 mutations. Results and limitationsIn the 97 men in the PRO population treated with talazoparib (BRCA1/2, n = 56), the mean (95% CI) EQ-5D-5L Index improved (all patients, 0.05 [0.01, 0.08]; BRCA1/2 subset, 0.07 [0.03, 0.10]), as did the EQ-5D VAS scores (all patients, 5.42 [2.65, 8.18]; BRCA1/2 subset, 4.74 [1.07, 8.41]). Improvements in the estimated overall change from baseline (95% CI) in the mean worst pain were observed in all patients (–1.08 [–1.52, –0.65]) and the BRCA1/2 subset (–1.15 [–1.67, –0.62]). The probability of not having had experienced deterioration of worst pain by month 12 was 84% for all patients and 83% for the BRCA1/2 subset. ConclusionsIn heavily pretreated men with mCRPC and DDR/HRR alterations, talazoparib was associated with improved HRQoL in all patients and the BRCA1/2 subset. In both patient groups, worst pain improved from baseline and the probability of not experiencing a deterioration in worst pain with talazoparib was high. Patient summaryWe show that talazoparib was associated at least with no change or improvements in health-related quality of life (HRQoL) and pain burden in men with metastatic castration-resistant prostate cancer and DNA damage response/homologous recombination repair gene alterations in the TALAPRO-1 study. These findings in patient-reported HRQoL and pain complement the antitumor activity and tolerability profile of talazoparib.

Abstract CT031: TALAPRO-1: Talazoparib monotherapy in metastatic castration-resistant prostate cancer (mCRPC) with tumor DNA damage response alterations (DDRm)– Exploration of genomic loss of heterozygosity (gLOH) and potential associations with antitumor activity

Abstract Background: TALAPRO-1 enrolled men with progressive mCRPC, measurable soft-tissue disease, and tumor DDRm involved directly or indirectly in homologous recombination repair (HRR) (11 gene panel). Men had received 1-2 taxane-based chemotherapy regimens and progressed on ≥1 novel hormonal therapy. The primary endpoint was objective response rate ([ORR] per RECIST 1.1; blinded independent central review [BICR]). Exploratory ad hoc biomarker analyses assessed gLOH and associations with antitumor activity. Methods: gLOH was calculated as previously described (Sokol et al., JCO Precis Oncol 2020; PMID: 32903788). Of 104 men in the HRR-deficient measurable disease population (hereafter referred to as the efficacy population), 55 were evaluable for gLOH, 45 were non-evaluable for gLOH, and four lacked central lab gLOH results. Potential association of gLOH high/low status with response was explored using two high/low thresholds: 8.8% based on literature showing that this threshold optimally distinguished prostate cancers bearing BRCA biallelic alterations from BRCA-wildtype (Sokol et al., JCO Precis Oncol 2020; PMID: 32903788), and an agnostic threshold based on the median gLOH score in TALAPRO-1 (9.2%) in the gLOH-evaluable efficacy population. Data cutoff was Sept 4, 2020 (primary completion date). Results: gLOH ranged from 1.39% to 30.2% in the gLOH-evaluable efficacy population. Based on the 8.8% gLOH threshold, ORR was significantly higher for gLOH-high (53.3% [16/30], 95% confidence interval [CI] 34.3-71.7%) vs gLOH-low (12.0% [3/25], 95% CI 2.5-31.2%; odds ratio [OR] 8.381, 2-sided P=0.0017; Fisher’s exact test). Similar results were yielded based on the 9.2% gLOH threshold. Next, potential associations of gLOH score with response within HRR gene alteration groups of the efficacy population were explored using the 8.8% threshold. Within the BRCA2 group, ORR was robust regardless of gLOH status, but was significantly higher for gLOH-high (70.6%, 12/17) than for gLOH-low (23.1%, 3/13) (P=0.0253). Within the ATM group, ORR was numerically higher for gLOH-high (50.0%, 2/4) than gLOH-low (0%, 0/6), but not significantly (P=0.1333). Radiographic progression-free survival (RECIST 1.1; BICR) in the gLOH-evaluable efficacy population was numerically superior for gLOH-high versus gLOH-low using either threshold (hazard ratio 0.68), but not significantly. Conclusions: Based on these retrospective, exploratory analyses of TALAPRO-1, gLOH-high status was associated with response within the gLOH-evaluable efficacy population. Further exploration of gLOH as a candidate predictive biomarker for talazoparib in prostate cancer is warranted. Citation Format: Johann S. de Bono, Niven Mehra, A. Douglas Laird, Elena Castro, Philippe Barthelemy, Remy Delva, Giorgio V. Scagliotti, Marco Maruzzo, Adam Stirling, Jean-Pascal Machiels, Herlinde Dumez, Vincent Renard, Julia F. Hopkins, Lee A. Albacker, Hsiang-Chun Chen, Cynthia G. Healy, Jijumon Chelliserry, Tanya Dorff, Karim Fizazi. TALAPRO-1: Talazoparib monotherapy in metastatic castration-resistant prostate cancer (mCRPC) with tumor DNA damage response alterations (DDRm)– Exploration of genomic loss of heterozygosity (gLOH) and potential associations with antitumor activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT031.

Outcomes of neoadjuvant (NA) and adjuvant (A) chemotherapy in geriatric patients with stage I-III triple-negative breast cancer (TNBC): A single institution experience.

e12522 Background: Older breast cancer patients have greater risk for toxicity with perioperative chemotherapy and poorer outcomes for stage I-III TNBC due to medical comorbidities and declining organ function. It is not clear whether use of anthracycline based chemotherapy regimens (ABC) delivers better outcomes than non-anthracycline taxane-based chemotherapy regimens (TBC) in this population. Methods: A single institution retrospective review of TNBC patients ≥65 treated with adjuvant and neoadjuvant chemotherapy at Moffitt Cancer Center from 2009 to December 2018 was conducted. Demographic, comorbidity, treatment, and toxicity variables were collected. Treatment toxicity was defined as dose reductions, dose delays, early discontinuations, unplanned hospitalizations, and grade 3-4 heme and non-heme toxicities. Eligible patients had stage I-IIII TNBC, were ≥65, and received NA or A chemotherapy at MCC. A validated frailty index (FI) was used to calculate comorbidity score. Kaplan Meier was used to estimate overall survival by regimen received, with log rank test to compare ABC and TBC groups. Results: A total of 79 patients met criteria for analysis, with mean age of patients receiving treatment was 71 (range 65-88). 41.8% of patients had stage I disease, 36.7% with stage II, and 21.5% with Stage III. 76% of patients with Stage III, 51.7% of Stage II, and 18% of stage I disease received ABC. There was a trend toward higher toxicity events in patients receiving ABC compared to TBC regimens, although not statistically significant (see Table). The mOS for patients receiving ABC was 43.5mo and 63.0 mo for patients receiving TBC, although not statistically significant (p=0.212). Conclusions: Geriatric patients with stage I-III TNBC were mostly able to successfully receive NA or A chemotherapy, although TBC may have better tolerability. Patients receiving TBC also had better survival, although not statistically significant and potentially confounded by patients with earlier stage or less aggressive tumors receiving TBC.[Table: see text]

Recognising Nail Changes Induced by Chemotherapy with Taxane-based Regimens and their Dermoscopic Confirmation: A Prospective Observational Study from Northern India

Introduction: Taxanes are chemotherapeutic agents used in a variety of solid tumours. They are known to cause cutaneous as well as nail changes which are temporally associated with intake of drug. Nail involvement is reported in literature from some parts of the world. Aim: To study the pattern of nail changes occurring due to taxane-based chemotherapy regimens in patients suffering from malignancies. Materials and Methods: A prospective observational study was carried out in a tertiary care hospital in GMC, Patiala, Punjab, India from October 2020 to September 2021. A total of 160 adult patients undergoing cancer chemotherapy with taxanes were included in the study. After taking detailed history, nail changes were examined and confirmed by dermoscopy. The data was analysed using Epi Info 7 by CDC and Chi-square test was used to calculate the p-value. Results: A total of 144 patients (87 females and 57 males), with the mean age of 53.8 years, were screened for six chemotherapeutic cycles. Drug-induced Nail Pigmentation (DINP) was the most common nail abnormality seen in 43/144 (30%) patients after third cycle and in 105/144 (73%) patients after the sixth cycle. The most common pattern was diffuse nail pigmentation 40/105 (39%) followed by longitudinal melanonychia 22/105 (21%) after six cycles. Maximum pigmentation 52/60 (86%) was observed in patients who received taxane+adriamycin+ cyclophosphamide combination. On onychoscopy, DINP appeared as thin grey regularly arranged parallel longitudinal lines on homogenous grey background. Conclusion: Taxanes cause varied pattern of nail changes with DINP being the most common. It ranges from longitudinal bands after three cycles to diffuse pigmentation after six cycles. These nail changes show temporal relation with dose, duration, number of drugs, and colour of skin. Dermoscopy is a novel non invasive method with a good diagnostic accuracy.

Flupirtine in the Management of Taxane-induced Pain in Cancer Patients.

Objectives:Paclitaxel and docetaxel are two commonly used chemotherapeutic agents in the treatment of various types of cancers. However, debilitating taxane-induced arthralgia and myalgia are among the most common adverse reactions associated with taxanes, which has greatly influenced medical practitioners. Most of the mild and moderate analgesics were found to be less effective in the management of taxane induced pain. So we used flupirtine, a non-opioid analgesic, in the treatment of taxane-induced pain.Materials and Methods:In this study, we analysed the baseline pain score and follow-up data of 60 patients receiving a taxane-based chemotherapy regimen. Baseline data of these study populations experiencing significant taxane-induced pain were compared with follow-up data after treating them with analgesic flupirtine (200 mg/day). The baseline and follow-up data representing pain were assessed with the help of the Visual Analogue Scale (VAS), and the quality of life was determined using the Brief Pain Inventory (BPI) scale questionnaire.Results:The mean baseline and follow-up VAS score was compared using paired sample t-test, which showed a significant reduction in taxane-induced pain after treatment with flupirtine (P < 0.001). Similarly, the mean BPI score representing the quality of life before and after treatment with flupirtine was compared, and a notable improvement in quality of life was seen after treatment with flupirtine. The mean and follow-up data of aspartate aminotransferase and alanine aminotransferase levels of patients were also compared to assess the adverse drug reaction profile of the drug, and the analyzed data was found to be statistically insignificant (no significant liver toxicity) which indicates that drug can be used effectively for a period of <2 weeks.Conclusion:We believe that flupirtine can be used as an effective analgesic in dire situations where patients require opioid analgesics for the management of taxane-induced pain, provided that the drug is given for <2 weeks to avoid drug-related hepatotoxicity.

Dose-Dense Docetaxel versus Weekly Paclitaxel following Dose-Dense Epirubicin and Cyclophosphamide as Adjuvant Chemotherapy in Node-Positive Breast Cancer Patients: A Retrospective Cohort Analysis.

Methods This study included patients from two prospective studies conducted in our institute from April 2007 to March 2009. Ninety-one women with axillary lymph node-positive breast cancer who had received four cycles of dose-dense epirubicin and cyclophosphamide were treated with either weekly paclitaxel (80 mg/m2) for 12 doses or biweekly docetaxel (75 mg/m2) for four cycles. Results After a median follow-up of 88 and 109 months, 11 (23.4%) and 10 (22.7%) patients had experienced disease recurrence (p = 0.16), while 10 (21.3%) and 5 (11.4%) patients had died in the paclitaxel and docetaxel arm, respectively (p = 0.56). No significant difference could be seen in 5-year DFS or OS among groups (HR: 0.58; 95% CI: 0.19–1.81, p = 0.35; HR: 0.58; 95% CI: 0.19–1.81, p = 0.35, respectively). Conclusion In conclusion, both evaluated adjuvant chemotherapy regimens have comparable effectiveness regarding DFS and OS.