Efficacy Of Docetaxel Research Articles

Tislelizumab Versus Docetaxel in Patients With Previously Treated Advanced NSCLC (RATIONALE-303): A Phase 3, Open-Label, Randomized Controlled Trial

IntroductionThe phase 3 RATIONALE-303 trial (NCT03358875) investigated the efficacy and safety of tislelizumab versus docetaxel in pretreated patients with advanced NSCLC. Here, we report the efficacy and safety results and describe the exploratory biomarker analyses. MethodsA total of 805 patients aged more than or equal to 18 years with locally advanced or metastatic squamous or nonsquamous NSCLC were randomized 2:1 to intravenous tislelizumab 200 mg or docetaxel 75 mg/m2 every 3 weeks. Co-primary end points were overall survival (OS) in the intent-to-treat (ITT) and programmed death-ligand 1 (PD-L1) tumor cell expression greater than or equal to 25% populations. The exploratory biomarker analyses included PD-L1 expression, tumor mutation burden, and gene expression profile. ResultsAt the prespecified interim analysis (August 10, 2020), the co-primary end point of OS in the ITT population was met, with a statistically significant and clinically meaningful improvement in OS with tislelizumab versus docetaxel (median 17.2 versus 11.9 mo, respectively; hazard ratio [HR] = 0.64, p < 0.0001). At the final analysis (July 15, 2021), the other co-primary end point of OS in the PD-L1 tumor cell greater than or equal to 25% population was further met (median 19.3 versus 11.5 mo, respectively; HR = 0.53, p < 0.0001), and OS continued to improve in the ITT population (median 16.9 versus 11.9 mo, respectively, HR = 0.66). Exploratory biomarker analyses revealed the potential association of NOTCH1–4 mutations with improved tislelizumab efficacy for both OS and progression-free survival, whereas tissue tumor mutation burden correlated with progression-free survival benefit, but not OS benefit. No new safety signals were identified. ConclusionsTislelizumab was found to have a significantly improved and long-term clinical benefit in OS versus docetaxel in pretreated patients with advanced NSCLC, regardless of PD-L1 expression.

EP08.02-160 A Pooled Efficacy and Safety Analysis of Anlotinib Plus Docetaxel in Advanced NSCLC Previously Treated with Immunotherapy

Immune checkpoint inhibitors (ICIs) are widely used in 1st -line or 2nd -line treatment of advanced NSCLC, but effective treatment after resistance to ICIs is still controversial. We previously reported that anlotinib plus docetaxel as 2nd-line treatment in advanced NSCLC showed better clinical efficacy than docetaxel alone in two phase II trials (ALTER-L016, ALTER-L018). Therefore, to further assess the efficacy and safety of anlotinib plus docetaxel in advanced NSCLC patients (pts) who had been pre-treated with ICIs by pooling raw data from the two phase II trials.

EP08.02-158 Final Analyses of ALTER-L018: A Randomized Phase II Trial of Anlotinib Plus Docetaxel vs Docetaxel as 2nd-line Therapy for EGFR-negative NSCLC

Docetaxel is one of the standard 2nd-line treatments for advanced non-small cell lung cancer (NSCLC), but the effect is limited. The combination of docetaxel and ramucirumab/nintedanib has demonstrated antitumor activity as 2nd-line therapy in advanced NSCLC. Anlotinib, an oral multi-target angiogenesis, can prolong both PFS and OS of refractory advanced NSCLC patients in phase III trial (ALTER0303). We conducted ALTER-L018 to evaluate improvement of the efficacy and safety of anlotinib plus docetaxel in EGFR-negative advanced NSCLC.

Multi-Institution Evaluation of Sequential Intravesical Gemcitabine and Docetaxel in the Treatment of Bacillus Calmette-Guerin Naïve Patients with Non-Muscle Invasive Bladder Cancer

<h2>Abstract</h2><h3>Introduction</h3> <b>:</b> Single agent intravesical chemotherapy regimens have historically compared unfavorably to Bacillus Calmette-Guerin (BCG) as initial treatment following resection for patients with high-risk non-muscle invasive bladder cancer (NMIBC). However, there have been few reports of multi-agent intravesical chemotherapy regimens in this setting. Our objective is to determine the efficacy of sequential intravesical gemcitabine and docetaxel (Gem/Doce) in BCG naïve patients with NMIBC. <h3>Patients and Methods</h3> <b>:</b> Collaborating institutions retrospectively identified patients with NMIBC who were treated with Gem/Doce between 6/2009 and 5/2018. An sub-cohort of patients without prior BCG and treated with Gem/Doce was identified. Treatment consisted of 6 weekly instillations of gemcitabine (1 gram/50mL) followed immediately by docetaxel (37.5 mg/50mL). Maintenance was utilized at the discretion of the treating physician. Recurrence-free survival (RFS), progression (PFS), and overall survival (OS) were assessed. Treatment tolerance and discontinuation were also evaluated. Statistical analysis was descriptive in nature. <h3>Results</h3> <b>:</b> Sixty-five patients were treated, with median age 75 years and median follow-up of 15.2 months. 77% had high-grade disease and 40% had carcinoma in-situ (CIS). RFS was 82%, 76%, and 66% at 6, 12 and 24 months respectively. Amongst patients with high-grade disease, high-grade RFS was 85%, 78%, and 66% at 6, 12, and 24 months respectively. One patient progressed to muscle-invasive bladder cancer. Limitations include the retrospective study design, small cohort size, and lack of a comparator arm. <h3>Conclusion</h3> : Intravesical Gem/Doce may be an effective treatment for BCG naïve NIMBC and warrants further investigation. <h3>MicroAbstract</h3> <b>:</b> BCG is the gold-standard adjuvant treatment following TURBT for high-risk NMIBC. Unfortunately, ongoing production shortages have diminished BCG availability. In a multi-institutional retrospective cohort of 65 patients, we f 56098[mound sequential intravesical gemcitabine and docetaxel (Gem/Doce) provided significant relief of recurrence (66% RFS at 2-years) and was well-tolerated (97% finished a full induction). Prospective evaluation of Gem/Doce is underway.

1234P Neoadjuvant camrelizumab plus docetaxel and carboplatin in locally advanced esophageal squamous cell carcinoma (ESCC): A prospective study

Neoadjuvant therapy followed by surgery has been recognized as an effective treatment for locally advanced ESCC. However, the pathological complete response (pCR) rate of neoadjuvant chemotherapy drugs was less than 10%. PD-1 inhibitors improve survival in patients（pts) with metastatic ESCC. Camrelizumab (anti-PD-1), has been approved as second-line treatment for ESCC. We conducted this study to evaluate the efficacy and adverse events (AEs) of camrelizumab plus docetaxel and carboplatin as neoadjuvant treatment in locally advanced ESCC.

EP08.02-136 Final Analysis of a Phase II Study: Anlotinib Plus Docetaxel in Patients with Previously Treated Metastatic Non-small Cell Lung Cancer

Advanced non-small cell lung cancer (NSCLC) patients with treatment failure of platinum-based doublet chemotherapy are still facing unmet needs. Anlotinib, as a multi-target anti-angiogenic agent, has shown potential chemo-sensitization in our pre-clinical research. Thereafter, we conducted this study to assess the efficacy and safety of anlotinib plus docetaxel in these patients who failed with previous chemotherapy. The interim analysis was formerly reported at the ESMO 2020 annual meeting, and currently we present the final efficacy and safety results.

Nab-Paclitaxel for Previously Treated Advanced Non–Small Cell Lung Cancer: Analysis of Safety and Efficacy for Patients With Renal Impairment

BackgroundRenal impairment can affect treatment tolerability and outcome in individuals with cancer. We aimed to assess the safety and efficacy of nab-paclitaxel for previously treated patients with advanced non–small cell lung cancer (NSCLC) and renal impairment enrolled in a phase 3 trial of nab-paclitaxel vs. docetaxel. Patients and MethodsPreviously treated NSCLC patients were randomly allocated (1:1) to receive docetaxel (60 mg/m²) on day 1 or nab-paclitaxel (100 mg/m²) on days 1, 8, and 15 of a 21-day cycle. Safety and efficacy outcomes of treatment were evaluated according to renal function. ResultsAmong the 503 patients enrolled in the phase 3 trial, 17.3% had moderate renal impairment (creatinine clearance of ≤50 mL/min, n = 49 for docetaxel and n = 38 for nab-paclitaxel) and 53.1% had mild renal impairment (creatinine clearance of >50 to ≤80 mL/min, n = 133 for docetaxel and n = 134 for nab-paclitaxel). For patients with renal impairment, the incidence of febrile neutropenia was lower in the nab-paclitaxel group than in the docetaxel group. The difference in treatment efficacy for nab-paclitaxel vs. docetaxel among patients with moderate or mild renal impairment was similar to that among the overall study population. ConclusionNab-paclitaxel was found to be tolerable and beneficial for previously treated patients with advanced NSCLC and mild or moderate renal impairment.

Real-world Evaluation of the Efficacy of Neoadjuvant DCF Over CF in Esophageal Squamous Cell Carcinoma: Propensity Score-matched Analysis From 85 Authorized Institutes for Esophageal Cancer in Japan.

We aimed to evaluate the efficacy of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy over cisplatin and 5-fluorouracil (CF) in patients with surgically resectable advanced esophageal squamous cell carcinoma (ESCC), using real-world data from 85 esophageal centers. JCOG1109 trial, which assessed the superiority of DCF over CF, and the superiority of chemoradiotherapy with CF over CF alone demonstrated the significant survival advantage of neoadjuvant DCF in overall survival (OS) over CF for ESCC. The ESCC patients who received neoadjuvant CF or DCF at 85 Japanese esophageal centers certified by the Japan Esophageal Society were retrospectively reviewed. After propensity score (PS) matching, the OS and recurrence-free survival were compared between CF and DCF. We initially enrolled 4781 patients. After data cleaning and PS matching using pretreatment variables, 1074 patients for each group were selected for subsequent analysis. There was no significant difference in the incidence of postoperative pneumonia and anastomotic leakage. In the survival analysis, OS was significantly longer in DCF group than CF group (hazard ratio, 0.868; 95% confidence interval, 0.770-0.978; P =0.02), as well as recurrence-free survival (hazard ratio, 0.850; 95% confidence interval, 0.761-0.949; P =0.004). The survival advantage of DCF was not observed in patients with 76 years old or older. Neoadjuvant DCF therapy showed a remarkable survival advantage in surgically resectable ESCC patients, especially in patients who were 75 years old or younger. The current real-world evidence will encourage recommendations for DCF as a standard regimen in neoadjuvant chemotherapy-based treatment strategy for ESCC.

Feiji Recipe Elevates the Quality of Life of the Elderly with Lung Cancer on Docetaxel Plus Cisplatin Chemotherapy

We have evaluated the effect of Feiji recipe on efficacy of docetaxel plus cisplatin treatment on the quality of life of the elderly with lung cancer. To this end, 186 lung cancer patients receiving treatment at the Second People’s Hospital of Lianyungang, Lianyungang City, Jiangsu Province were recruited between January 2017 and December 2021 and randomly divided into control (receiving docetaxel + cisplatin) and treatment (receiving docetaxel + cisplatin + Feiji recipe) groups of 93 patients. Both groups received hydration on the day of cisplatin use and received preventive treatment for emesis, liver protection, acid suppression, and mucosal protection. Post-treatment depletion of cluster of differentiation 3 protein, cluster of differentiation 4 protein, and cluster of differentiation 4 protein/cluster of differentiation 8 protein levels in the treatment group were significantly (P &lt; 0.05) ameliorated/enhanced compared to the control group. Cluster of differentiation 3 protein and cluster of differentiation 4 protein/cluster of differentiation 8 protein levels in the treatment group were upregulated relative to controls (P &lt; 0.05), whereas cytokeratin 19 fragment antigen, cancer antigen 125, and carcinoembryonic antigen levels in the treatment group were depleted relative to controls after treatment (P &lt; 0.05). However, there was no significant difference in natural killer cell counts in the two groups before and after treatment (P &gt; 0.05). The overall treatment effectiveness (74.18% and 90.32%) and the progressive disease rates (25.82% and 9.68%) in the control and treatment groups, respectively (P &lt; 0.05). The physical/emotional/cognitive/role function scores in the treatment group were markedly increased compared to the control group (P &lt; 0.05). In conclusion, Feiji recipe markedly enhanced efficacy of all measures of treating lung cancer by docetaxel + cisplatin.

P66-12 The efficacy of trastuzumab, pertuzumab, and docetaxel in patients with HER-2-positive metastatic breast cancer

Metastatic breast cancer is the most advanced stage of breast cancer among women. Based on the results from a clinical trial (CLEOPATRA), pertuzumab combined with trastuzumab and docetaxel were selected as the standard first-line therapy for HER2-positive metastatic breast cancer. This systematic review aims to evaluate the efficacy of trastuzumab, pertuzumab, and docetaxel in patients with metastatic breast cancer.

Efficacy and tolerability of fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in unselected patients with advanced gastric and gastroesophageal cancer: does age really matter?

Fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) regimen has shown strong efficacy as perioperative therapy for patients with locally advanced gastric (GC) and gastroesophageal (AEG) carcinoma. In the palliative situation, FLOT is recommended only for young fit patients. Data of efficacy and tolerability of FLOT in elderly patients are scarce and controversial. Thus, this study aimed to provide real-life experience of elderly patients with GC and AEG treated with FLOT as first-line palliative chemotherapy. Patients with advanced or metastatic GC or AEG and treated with FLOT as first-line palliative therapy between 2010 and 2021 were analyzed. Patients were grouped into < 65 years old (n = 35) and ≥ 65 years old (n = 22) groups. Overall survival (OS), progression-free survival (PFS), feasibility and toxicity were analyzed. The median OS was 10.4months with no significant difference between both groups (HR 0.86; 95% CI 0.48, 1.57; p = 0.632). The ECOG performance status showed powerful influence on OS in the subgroup analysis with median OS of 12.3months for ECOG = 0 compared to 5.0months for ECOG ≥ 1 (p = 0.015) as well as in multivariate analysis (HR 2.62; 95% CI 1.36, 5.04; p = 0.004). In the present study the ECOG performance status showed a stronger prognostic value than patient age in FLOT as first- line therapy in a real-life cohort with advanced and metastatic GC and AEG. The performance status should therefore be considered in the therapeutic decision making of elderly patients with GC and AEG.

Abstract 400: Functional, structural and binding studies of the atypical ER-resident protein FKBP7, a potential target in chemoresistant prostate cancer

Abstract Background: Metastatic Castration Resistant Prostate Cancer (mCRPC) is the latest stage of Prostate Cancer (PCa). Despite the use of taxane-based chemotherapies Docetaxel and Cabazitaxel, mCRPC remains lethal due to chemoresistance. We recently identified FKBP7 as a potential therapeutic target of interest in PCa. FKBP7 is overexpressed in taxane-resistant PCa cells and impacts both cell proliferation and Docetaxel efficacy in chemoresistant models. We demonstrated FKBP7 affects translation and binds to the translation initiation complex eIF4F. FKBP7 is an ER-resident FKBP, but its properties remain poorly described. Methods: FKBP7 expression upon chemotherapy treatment was assessed by Western Blot and correlation between FKBP7 expression and clinical prognosis was examined on public cancer databases. Subcellular localization of FKBP7 was addressed by digitonin-based fractionation. Finally, FKBP7-predicted structure was obtained with structural modeling servers and sequence alignments were performed on AliView. We then produced and purified the recombinant catalytic domain of FKBP7 and collected high quality 15N HSQC NMR spectra. Afterwards, we examined its interaction with well-known FKBP ligands. Results: Increased FKBP7 expression was observed upon treatment with several cytotoxic chemotherapies in PCa-cell lines, and TCGA data underlined FKBP7 impacts survival in other cancers than PCa. Together, this suggests an enlarged potential involvement of FKBP7 in adaptive resistance. Mechanistically, in taxane-resistant models, FKBP7 overexpression did not result from higher protein stability but rather from a transcriptional regulation. Preliminary results of subcellular fractionation showed FKBP7 is present in the Endoplasmic Reticulum (ER) and seems to localize in the cytosol, independently of proteasomal degradation. We also confirmed FKBP7 is N45-glycosylated and observed that cytosolic-FKBP7 appears mainly glycosylated. This suggests that the ER-resident FKBP7 could be refluxed in the cytosol depending on its glycosylation state to regulate the activity of the cytosolic eIF4F complex. We are currently validating this hypothesis. At last, structural modeling predicted a FKBP-type fold with a potential FKBP7 substrate specificity as its catalytic pocket presents distinct composition for charge and bulkiness compared to other FKBPs. Accordingly, FKBP7 strongly binds Rapamycin and Everolimus, but surprisingly not FK506, confirming a selective binding profile. Conclusion: Our work depicts the recently identified FKBP7/eIF4F pathway in PCa-resistance and points atypical properties for the ER-resident FKBP7. It also indicates FKBP7 could be a druggable target in adaptive resistance of other solid cancers. Besides, we gathered original data on its structure and specificity for future drug-targeting strategies. Citation Format: Luce Dreno, Carolina Tiraboschi, Sofian Lacoste, Sofia Calpe Gomez, Marine F. Garrido, Matthieu Bertrand, Mariana Tannoury, Eric Jacquet, Naima Nhiri, Yohann Loriot, Karim Fizazi, Daniel Compagno, Nadine Assrir, Ewen Lescop, Anne Chauchereau. Functional, structural and binding studies of the atypical ER-resident protein FKBP7, a potential target in chemoresistant prostate cancer [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 400.

Abstract CT558: Capmatinib vs docetaxel as second- or third-line therapy in patients with locally advanced or metastatic METex14-mutated NSCLC: The GeoMETry-III trial

Abstract Background: MET dysregulation is a poor prognostic factor in advanced non-small cell lung cancer (NSCLC). MET exon 14 skipping (METex14) mutations occur in ~3% of patients with NSCLC. There is limited evidence of the efficacy of standard therapies, such as chemotherapy or immunotherapy, in patients with METex14-mutated advanced NSCLC. Capmatinib, a MET inhibitor (METi), is approved for the treatment of adult patients with metastatic METex14-mutated NSCLC, based on the results of the phase 2 GEOMETRY mono-1 study. Results (data cutoff: September 18, 2020) of this study in patients with METex14-mutated NSCLC treated with capmatinib showed an overall response rate (ORR) of 66.7% in first line (N=60), 51.6% in second line (N=31) and 40.6% in second- or third-line (2/3L; N=69). GeoMETry-III (NCT04427072) is a multicenter, open-label, randomized, controlled, global, phase 3 trial that is further evaluating the efficacy and safety of capmatinib vs docetaxel in the 2/3L setting in patients with METex14-mutated NSCLC. Methods: This study began enrollment in September 2020 and is currently recruiting adult patients with EGFR wild-type, ALK-negative, stage IIIB/IIIC/IV METex14-mutated NSCLC, who have progressed on 1 or 2 prior lines of systemic therapy for advanced/metastatic disease and are candidates for single-agent docetaxel. Other eligibility criteria include ≥1 measurable lesion per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), an Eastern Cooperative Oncology Group performance status of ≤1 and no prior treatment with any METi or hepatocyte growth factor-targeting therapies. Patients with neurologically unstable, symptomatic central nervous system (CNS) metastases or those requiring increasing doses of steroids ≤2 weeks prior to study entry to manage CNS symptoms are excluded. Around 90 patients will be randomized 2:1 to receive either oral capmatinib 400 mg twice daily or intravenous docetaxel 75 mg/m2 every 21 days. Randomization is stratified by number of prior lines (1 or 2) of systemic therapy. Patients meeting protocol-specified eligibility criteria can cross over from the docetaxel to the capmatinib arm after blinded independent review committee (BIRC)-confirmed progressive disease as per RECIST 1.1.The primary endpoint is progression-free survival (PFS) by BIRC per RECIST 1.1. The key secondary endpoint is ORR by BIRC per RECIST 1.1. Other secondary endpoints include investigator-assessed ORR and PFS; duration of response, time to response and disease control rate (DCR) by BIRC and investigator; overall survival; safety; pharmacokinetics; patient-reported outcomes; overall intracranial response rate, intracranial DCR, duration of- and time to- intracranial response by BIRC per the Response Assessment in Neuro-Oncology Brain Metastases criteria in patients with baseline CNS lesions. Citation Format: Pierre Jean Souquet, Sang-We Kim, Johan F. Vansteenkiste, Anna Robeva, Aline Jary, Sabine Glaser, Alejandro Yovine, Juergen Wolf. Capmatinib vs docetaxel as second- or third-line therapy in patients with locally advanced or metastatic METex14-mutated NSCLC: The GeoMETry-III trial [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 CT558.

Abstract 5365: Repositioning nicardipine as a novel targeted therapy for chemoresistant prostate cancer

Abstract Background: It is imperative to develop novel therapeutics to overcome chemoresistance, a major obstacle in the clinical management of prostate cancer (PCa) and other cancers. Drug repositioning is being pursued as an attractive approach due to its potentially lower overall development costs and shorter timelines. The purpose of this study is to investigate the preclinical efficacy and mechanism of action of nicardipine, an FDA-approved hypertension drug, as a new treatment against chemoresistant prostate cancer. Methods: A panel of FDA-approved non-oncology drugs was screened for their selectivity and potency to inhibit chemoresistant PCa cells using a two-tier phenotypic screening platform (Theranostics, 2021, 11(14): 6873-6890). The mechanism of action of potential candidate(s) was evaluated using in silico docking, cellular and molecular assays in ARCaPE-shEPLIN and C4-2B-TaxR, two independent chemoresistant PCa cell lines. The in vivo efficacy was evaluated in clinically-relevant xenograft models of PCa. Results: Nicardipine exhibited high selectivity and potency against chemoresistant PCa cells via effectively inducing apoptosis and cell cycle arrest. The IC50 of nicardipine was determined as 0.5 μM and 2.1 μM in ARCaPE-shEPLIN and C4-2B-TaxR cells, respectively. Mechanically, nicardipine targeted a novel non-canonical enhancer of zeste homolog 2 (EZH2) signal pathway in chemoresistant PCa cells. Specifically, nicardipine might bind embryonic ectoderm development (EED), interrupt the integrity and stability of the polycomb repressive complex 2 (PRC2), reduce the phosphorylation and expression of EZH2, and subsequently inhibit downstream effectors including signal transducer and activator of transcription 3 (Stat3), S-phase kinase-associated protein 2 (SKP2), ATP binding cassette B1 (ABCB1) and survivin. In animal models, as a monotherapy, nicardipine significantly suppressed the intratibial growth of chemoresistant C4-2B-TaxR xenografts, with an average PSA level of 43.47 ng/ml, 36.63 ng/ml, and 28.78 ng/ml for the vehicle control, docetaxel, and nicardipine groups at the endpoint, respectively (p &amp;lt; 0.05 between the nicardipine group and the vehicle control or docetaxel groups). As a combination regime, nicardipine synergistically enhanced the efficacy of docetaxel against the intratibial growth of C4-2 xenografts, with an average PSA level of 79.17 ng/ml, 49.04 ng/ml, 42.80 ng/ml, and 23.23 ng/ml for the vehicle control, docetaxel, nicardipine, and combination groups at the endpoint, respectively (p &amp;lt; 0.0001 or 0.01 between the combination group and the vehicle control or docetaxel groups, respectively). Conclusion: These results demonstrated that, for the first time, nicardipine could be a novel EED inhibitor that has the potential to be promptly tested in PCa patients to overcome chemoresistance and improve clinical outcomes. Citation Format: Xin Li, Alira Danaher, Jason M. Wu, Yifei Wu, Zhong-Ru Xie, Nicholas Cook, Nathan Bowen, Daqing Wu. Repositioning nicardipine as a novel targeted therapy for chemoresistant prostate cancer [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 5365.

Abstract 1917: Accurate modeling of HER2 positive breast cancer disease progression with a biophysical modeling software

Abstract Breast cancer (BC) progression during NAT is associated with development of distant metastases, positive LN status, and decreased OS/RFS. These can occur in the context of clinical trials and therapy de-escalation, where the focus is on delivering effective NAT to patients while reducing drug toxicity. The risks added by disease progression underscore the need for early identification of NAT progressors. To this end, we replicated the NeoSphere study in silico using TumorScope (TS), a biophysical modeling software, focusing on predicting disease progression during NAT. The NeoSphere trial studied the efficacy of docetaxel (T), pertuzumab (P), and trastuzumab (H) in combination with one another over 254 operable BC patients distributed across four study arms. We selected past BC patients with accompanying standard of care clinical data that matched NeoSphere sample composition based on patient and tumor characteristics. A total, 144 patients were included across four study arms (TH, THP, HP, and TP). Parameters from the NeoSphere study were mirrored where possible. Simulation generated volume trajectories of individual tumor’s response to therapy. Disease progressors were identified based on tumor volume at the final simulation timepoint compared to the first simulation timepoint. We then compared group means and proportions between progressors and responders using Welch’s two-sample t-test, and Fisher’s exact test, respectively. We replicated the NeoSphere trial using TS. pCR rates across study arms closely mirrored those of the actual trial. In the HP arm of our trial, we identified 12 (12/144) progressors. No difference was found when comparing it to that observed in the NeoSphere trial (p=1.00, OR=1.12). As expected, percent change in tumor volume from initial to final timepoints for the progressor group was significantly higher than the responder group (n=121, t=19.2, p=1.5x10-10, mean progressor=38.7, mean responder=-75.9). The progressor group was enriched with higher grade tumors (t=2.85, p=0.01), as well as HR-negative tumors (p=0.002, OR=7.54) compared to the responder group, and had lower HER2 receptor FISH ratios (t=-3.4, p=0.002). There were no differences observed between groups age, cancer subtype, or AJCC tumor stage (p&amp;gt;0.05). After trial replication, we identified clinical features that separated progressors from responders, which are being assessed for development of individualized predictive biomarkers of disease progression. While work is ongoing in the field to identify biomarkers of BC progression, it is evident that single markers are not sufficient. Comprehensive, multi-modal biomarkers of disease progression must be developed and applied to patient sub-populations to garner effective predictions. Using biophysical simulations, we are able to investigate the impact of drug delivery/sensitivity, metabolism, and spatial heterogeneity on BC progression. Citation Format: John Pfeiffer, Tim Foley, Eduardo Braun, Anu Antony, Lance Munn, Joseph R. Peterson, John A. Cole, The SimBioSys Team. Accurate modeling of HER2 positive breast cancer disease progression with a biophysical modeling software [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 1917.

Artificial Intelligence Segmentation Algorithm-Based Optical Coherence Tomography Image in Evaluation of Binocular Retinopathy.

On account of optical coherence tomography (OCT) images with intelligent segmentation algorithm, this article investigated the clinical efficacy and safety of docetaxel combined with fluorouracil. In this study, 60 patients with retinopathy treated in hospital were selected as the research objects. There were 30 cases in each group, the control group was treated with conventional images, and the observation group was treated with algorithm-based OCT images. Intelligent segmentation boundary detection algorithm, boundary tracking, and contour localization were proposed and applied to the OCT images of patients to analyze features and measure corneal thickness in OCT images with high signal-to-noise ratio and noise and artifacts. Objects in the control group were treated with semiconductor laser, and those in the observation group were treated with OCT images with algorithm in addition to the treatment of the control group. The results showed that the number of images with relative error of 2 was more, and the number of images with relative error of -2 was the least. The average thickness of high-quality images was 562.7 μm, and the average thickness of images with noise and artifacts was 573.8 μm. The total effective rate of the observation group was 96.67%, which was significantly higher than that of the control group (80%), and the curative effect and physical improvement rate of the observation group were significantly better than that of the control group (P < 0.05). All in all, the feature extraction of OCT images and corneal measurement proposed in this study had a good measurement effect, and the method had the advantages of strong anti-interference ability and high measurement accuracy.

EVOKE-01: A phase 3 study of sacituzumab govitecan (SG) versus docetaxel in patients with non–small cell lung cancer (NSCLC) progressing on or after platinum-based chemotherapy and checkpoint inhibitors.

TPS9149 Background: Single-agent chemotherapy, such as docetaxel, is the standard of care in patients with metastatic NSCLC who progressed on platinum-based therapy and checkpoint inhibitors. However, docetaxel is associated with poor survival (median overall survival [OS] of &lt; 1 year); thus, novel agents are needed to further improve outcomes in this setting. SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. In a single-arm expansion of the phase 1/2 IMMU-132-01 basket study of advanced epithelial cancers (NCT01631552), SG demonstrated an objective response rate (ORR) of 17% and median OS of 9.5 months, with a manageable safety profile in 54 patients with metastatic NSCLC who had multiple prior therapies (Heist RS, et al. J Clin Oncol. 2017). EVOKE-01 randomized phase 3 study was designed to further evaluate SG in patients with metastatic NSCLC. Methods: EVOKE-01 (NCT05089734) is an open-label, global, multicenter, randomized, phase 3 study comparing the efficacy and safety of SG vs docetaxel in patients with metastatic NSCLC. Key eligibility criteria include age ≥18 years, pathologically documented stage IV NSCLC at time of study entry, and progression after platinum-based chemotherapy and anti-PD(L)1 therapy given either in combination or sequentially. Patients with EGFR, ALK, or other known actionable genomic alterations must have also received treatment with ≥1 approved appropriate TKI. Other inclusion criteria are ECOG performance status 0-1 and adequate hematologic, hepatic, and renal function. Patients with prior treatment with topoisomerase inhibitors are excluded. Patients are randomized 1:1 to receive intravenous SG (10 mg/kg on day 1 and 8) or docetaxel (75 mg/m2 on day 1) in 21-day cycles until progressive disease or unacceptable toxicity. Stratification is based on predominant histology (squamous vs nonsquamous), best response to prior immune therapy (PD/SD vs CR/PR), and prior therapy for actionable genomic alteration (yes vs no). The primary endpoint is OS. Key secondary endpoints include progression-free survival, ORR, duration of response, and disease control rate, as assessed by investigator RECIST v1.1, mean change from baseline in NSCLC-SAQ total score and shortness of breath, and safety. This study plans to enroll ̃520 patients globally and is open for recruitment. Clinical trial information: NCT05089734.

Combi-TED: A multicenter, phase II, open-label, randomized trial evaluating efficacy of OSE2021 plus docetaxel or OSE2021 plus nivolumab as second-line therapy in metastatic NSCLC progressing after first-line chemo-immunotherapy.

TPS9140 Background: First line combination of chemotherapy and immune checkpoint inhibitors (ICIs) improves overall survival (OS) compared with chemotherapy alone in non-small cell lung cancer (NSCLC) patients. However, only few options are available at chemoimmunotherapy failure, with docetaxel representing the standard of care. Tedopi is a cancer vaccine which stimulates killer T cells, currently under development for the therapy of HLA-A2+ lung cancer. In the ATALANTE-1 Phase III trial (EudraCT no. 2015-003183-36), Tedopi provided clinical benefits in patients with advanced NSCLC who failed to respond to checkpoint inhibitors. Given the need for new therapeutic options in patients failing first-line chemo-immunotherapy and the encouraging preliminary data with Tedopi, there is a strong rationale for investigating the activity of Tedopi plus nivolumab or Tedopi plus docetaxel in patients with metastatic NSCLC failing standard first-line therapy. Methods: This is a phase II, non-comparative, randomized multicenter study assessing the combination of Tedopi with docetaxel or nivolumab in NSCLC patients failing after first-line chemoimmunotherapy (EudraCT no. 2020-005170-10). All NSCLC patient candidates for second-line therapy are considered eligible for the study if they are HLA-A2+, with no evidence of EGFR mutations or ALK/ROS1 rearrangement and if they progressed after at least 4 cycles of previous first-line chemo-immunotherapy. Patients are randomly assigned to Tedopi plus docetaxel, Tedopi plus nivolumab (treatment arms) or docetaxel monotherapy (standard arm). The primary endpoint is 1-year OS rate. Secondary endpoints include OS, 2-year OS rate, progression-free survival (PFS), objective response rate (ORR), and safety. An explorative analysis of the correlation of efficacy with several tumor or blood biomarkers (PD-L1 expression, tumor mutational burden, Tedopi neoantigen expression, T cell infiltration), is also performed. Sample size was calculated assuming a 1-year OS rate in the standard arm of 20%. According to the single-stage design, in both treatment arms a 1-year OS rate of 20% would imply that treatment does not warrant further investigation and a 1-year OS rate of 40%, would imply that treatment has a sufficient activity. With a one-sided significance level of 5% and a power of 80%, a total number of 105 patients (35 per treatment arm) need to be enrolled. At the drafting of this abstract, 7 patients have already been enrolled. Total follow-up will be 24 months from last enrolment, for an approximate duration of 48 months. Clinical trial information: NCT04884282.

Long-term outcomes of a randomized controlled clinical trial comparing the efficacy of cabazitaxel versus docetaxel as second-line or above therapy in recurrent head and neck cancer.

e18008 Background: Long term outcomes (&gt; 2 years or above) are rarely reported in studies with second line or beyond systemic therapies in head and neck squmouas cell carcinoma (HNSCC). Methods: Recurrent or relapsed adult HNSCC, with ECOG PS 0-2 who have been exposed to at least one line of chemotherapy were 1:1 randomized between Docetaxel (75 mg/m2) and Cabazitaxel (20 mg/m2). The chemotherapy was given till progression or development of intolerable side effects. The outcomes reported are long term overall survival(OS) and progression free survival (PFS) and factors impacting overall survival. Results: On the intention to treat analysis (n = 92), at the time of data censoring, 92 patients had died. The median overall survival was 112 days (95% CI 81 to 178 days) in the cabazitaxel arm versus 192 days (95% CI 153 to 259 days) in the Docetaxel arm (P = 0.048). In cabazitaxel arm, the one year OS was 6.5% (95% CI 1.6-16.06), 2 year OS was 2.17% (95% CI 0.17-9.95) and 3 years was 2.17% (95% CI 0.17-9.95). While the corresponding figures in the docetaxel arm were 21.7% (95% CI 11.23-34.46), 0% and 0%. The median progression-free survival was 21.0 days (95% CI 16.0-42.0 days) in the Cabazitaxel arm versus 57.5 days (95% CI 26.0-85.0 days) in the Docetaxel arm (P = 0.02). Among the tested factors age (p = 0.037) and site of primary(p = 0.023) had an impact on OS. Conclusions: In this phase 2 randomised study, cabazitaxel has inferior PFS and OS than docetaxel. Hence docetaxel remains the option of choice when cytotoxic chemotherapy needs to be used as second line or beyond setting in HNSCC. Clinical trial information: CTRI/2015/06/005848.

Ccl3 enhances docetaxel chemosensitivity in breast cancer by triggering proinflammatory macrophage polarization

BackgroundAlthough the antitumor efficacy of docetaxel (DTX) has long been attributed to the antimitotic activities, its impact on the tumor microenvironment (TME) has recently gained more attention. Macrophages are a...