Carboplatin-paclitaxel Chemotherapy Research Articles

Abstract PO1-06-04: Immune checkpoint inhibitors for triple-negative inflammatory breast cancer (INCORPORATE): an international multicenter retrospective analysis

Abstract Background: Inflammatory breast cancer (IBC) is an aggressive clinical presentation of breast cancer (BC). Immune checkpoint inhibitors (ICIs) combined with chemotherapy provided an overall survival (OS) benefit in the metastatic setting and an even-free survival (EFS) benefit in patients (pts) with early triple-negative (TN) BC, respectively. Patients with TN-IBC were under-represented or excluded in pivotal trials and commonly not evaluated in subgroup analyses. Methods: We conducted a retrospective, multicenter, international, observational study to evaluate the clinical benefit of ICIs in pts with TN-IBC (defined as cT4d per AJCC TNM, 8th ed., ER < 1% and PgR < 1%, HER2: negative). Pts with early-stage TN-IBC were included if they received an ICI combined with neoadjuvant chemotherapy (NACT) (Group 1). Pts with metastatic TN-IBC were included if they received ICI monotherapy or in association with first-line chemotherapy (Group 2). Treatment was administered according to guideline recommendations (in PD-L1+ metastatic IBC and regardless of PD-L1 in early IBC), in clinical trials, or off-label (regardless of PD-L1 expression status in metastatic IBC). Endpoints were pathological complete response (pCR) and 1-year EFS rate for group 1 (calculated from date of first cycle of NACT to any recurrence or death), and progression-free survival (PFS) for group 2. Correlative analyses were provided (significance at p-value < 0.05). Results: We included 59 pts from 8 international referral centers. 15 pts had early IBC (Group 1), and 44 pts had metastatic disease (Group 2). Patient characteristics and outcomes are shown in Table 1. Among the 15 pts from Group 1, 10 received anthracycline, taxane and carboplatin-based (AC-CbT) NACT with pembrolizumab, 3 neoadjuvant paclitaxel-carboplatin chemotherapy with pembrolizumab, 2 neoadjuvant nab-paclitaxel with atezolizumab. One pt progressed on NACT, 2 pts are still receiving NACT. Among 13 pts evaluable for response, 6/13 (46%) achieved a pCR. After a median follow-up of 7.1 months, the median EFS was 12.9 months and the 1-year EFS rate was 70%. The median OS was 15.7 months. Among pts from Group 2, PD-L1 status was positive (IC 1% or CPS 10) in 27/44 pts (61%), negative in 5/44 pts (11%) and unknown in 6/44 pts (13%). At a median follow-up of 24.3 months, median PFS and OS were 4.1 and 15.7 months. As backbone chemotherapy in first line setting, 6 pts received AC-CbT regardless of PD-L1 status (mPFS: 8.6 months), 21 taxane-based/anthracycline-free chemotherapy (mPFS: 5.3 months), 14 other chemotherapy regimens (mPFS: 2.1 months) and 3 single-agent immunotherapy (mPFS: 50.1 months). Three of 6 patients who received AC-CbT underwent surgery and radiotherapy. In Group 2, after adjusting for the number of metastatic sites (>1 vs. 0-1), PD-L1 status (positive vs. negative vs. unknown) and de novo metastatic disease (yes vs. no), AC-CbT chemotherapy (HR 0.05; 95% CI: 0.01-0.56; p=.015) and taxane-based chemotherapy (HR 0.20; 95% CI: 0.06-0.68; p=.009) were both associated with longer PFS. Conclusions: This multicenter retrospective analysis of TN-IBC treated with combination of chemotherapy and IOs showed relatively low pathology response, EFS and clinical benefit suggesting need to further investigate the role of immunotherapy in this aggressive disease. Table 1. Patient characteristics and outcomes Citation Format: Carmine Valenza, Dario Trapani, Paola Zagami, Gabriele Antonarelli, Luca Boscolo Bielo, Eleonora Nicolò, Joana Mourato Ribeiro, Lorenzo Guidi, Carolina REDUZZI, Martina Spotti, Elisabetta Munzone, Javier Cortés, Barbara Pistilli, Sara Tolaney, Naoto Ueno, Rachel Layman, Massimo Cristofanilli, Lisa Carey, Filipa Lynce, Wendy Woodward, Giuseppe Curigliano. Immune checkpoint inhibitors for triple-negative inflammatory breast cancer (INCORPORATE): an international multicenter retrospective analysis [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 PO1-06-04.

Abstract 5532: Differences in immune contexture across metastatic sites and tissue compartments in ovarian cancer

Abstract Introduction: Characterizing the immune contexture within the tumor microenvironment (TME) can provide valuable biological insights that may impact treatment regimens and improve clinical outcomes. The advent of neoadjuvant chemotherapy has provided a unique opportunity to study matched, pre- and post- treatment sample pairs, but these samples are often obtained from different metastatic sites. Innate differences in the immune profiles across metastatic sites could therefore be a confounding factor when attempting to determine treatment-related effects. Furthermore, immune contexture can also vary by region within the TME, so results could vary depending on the regions of interest (ROIs) selected for analysis. Methods: 36 matched, advanced primary ovarian cancer samples were obtained pre- and post- treatment with neoadjuvant chemotherapy aimed at reducing tumor burden. The first biopsy was taken at the time of initial diagnosis, whereas the second biopsy was collected after 3-4 rounds of carboplatin paclitaxel chemotherapy. Each slide was processed using a 26-plex multiplex immunohistochemistry (mIHC) assay, which interrogates immune cell densities and functional states for a broad range of immune cell populations, including CD8+ T cells, Tregs, TH1s, B cells, dendritic cells (DCs), granulocytes, macrophages, and monocytes. Tumor and stroma ROIs were selected by a board-certified pathologist using H&E slides immediately adjacent to the mIHC samples, and cell densities were calculated separately for each of the two tissue compartments. Results: When comparing pre-treatment samples from the omentum (n = 8) with post-treatment samples from the omentum (n = 14), all of the statistically significant changes were found within the tumor compartment, with higher densities in the post-treatment samples for CD8+ T cells (p = 0.009), Tregs (p = 0.012), DCs (p = 0.04), and monocytes (p = 0.027). In contrast, when comparing post-treatment samples from the omentum (n = 14) and the ovary (n = 14), all of the significant differences were found within the stroma compartment, with higher densities in the omentum for CD8+ T cells (p = 0.002), Tregs (p = 0.043), TH1s (p = 0.003), and macrophages (p = 0.048). Conclusions: These results demonstrate that the site of metastasis can be a significant confounding factor when making statistical comparisons between variables such as timepoint and that differences in immune cell density before and after treatment may be more apparent in the tumor, while differences between tissue types may be more apparent in the stroma. Further research into the immune profiles of different metastatic sites is warranted, but our findings demonstrate the importance of considering both tissue type and ROI selection strategy when designing a study with the intent to detect differences between longitudinal patient samples. Citation Format: Benjamin Tate, Elias Pavlatos, Teresa Kim, Kiaya Wilson, Erik Cid, Jian Rao, Gottfried Konecny, Joanna Pucilowska. Differences in immune contexture across metastatic sites and tissue compartments in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5532.

Improving cognitive function with intermittent dose escalation of curcumin extract in chemotherapy-induced cognitive impairment patients: a randomized controlled trial

AbstractChemotherapy-induced cognitive impairment (CICI) is an impairment of memory, learning power, concentration, reasoning, executive function, attention, and visuospatial during and after chemotherapy exposures. No proven safe and effective therapeutic regimen are available to improve cognitive function in CICI patients. To evaluate the safety and effectiveness of curcumin extract to improve cognitive function in CICI patients. This study was a double-blind randomized controlled trial clinical trial in patients with cervical carcinoma who underwent a carboplatin-paclitaxel chemotherapy regimen from March to October 2021 at single center hospital. Subjects divided into two groups that received curcumin and placebo caplets by dose escalation method from 240 to 400 mg intermittently (14 days on and 7 days off) between chemotherapy cycles. Cognitive function was evaluated pre- and post-therapy using the AFI questionnaire, Stroop test, and MoCA-Ina. A total of 78 subjects were equally divided into the treatment and control groups. The percentage of drop-out, mortality, and adverse drug response were relatively comparable between each treatment arm. The group of subjects receiving curcumin extract experienced clinically and statistically significant improvements in cognitive function based on the Stroop test (∆ median 8.57 vs. 2.46; Z − 4.503 vs. − 1.762; p < 0.0001 vs. 0.078) and MoCA- Ina (∆ mean 1.53 vs. 0.72; Z − 2.99 vs. − 2.05; p < 0.003 vs. 0.04) versus placebo in between-group and between-subject analyses, respectively. Administration of curcumin extract with intermittent dose escalation regimen proved to be safe and able to improve cognitive function of CICI patients clinically and statistically significant.

Selective adjuvant radiation therapy for distant lymph node metastasis in patients with stage 4B epithelial ovarian cancer: a case series

Although the efficacy of surgery followed by taxane- and platinum-based systemic chemotherapy has been clearly demonstrated in the standard first-line treatment of epithelial ovarian cancer, the role of radiation therapy for distant lymph node metastasis in patients with epithelial ovarian cancer is not well-established due to a lack of reported studies. We identified four patients who underwent selective adjuvant radiation therapy for neck and para-aortic lymph node lesions after primary debulking surgery between 2020 and 2022, followed by platinum-based chemotherapy for stage 4B high-grade serous ovarian cancer. Through a retrospective review of medical records, we analyzed patient clinicopathologic features, treatment course, and imaging findings. The median age was 49.25 years (range, 46–54 years). All patients had the International Federation of Gynecology and Obstetrics stage 4B disease. Following primary debulking surgery, all patients received weekly paclitaxel-carboplatin chemotherapy and maintenance treatment with poly(ADP-ribose) polymerase (PARP) inhibitors. All patients received selective adjuvant radiation therapy for neck and para-aortic lymph node metastasis before PARP inhibitor maintenance. The median follow-up time was 36.75 months (range, 19–45 months). All patients achieved a complete response. None of the patients experienced disease recurrence or died during the follow-up period. The management of distant lymph node metastasis in patients with epithelial ovarian cancer remains a matter of debate. Selective adjuvant radiation therapy in first-line treatment for ovarian cancer appears to be a feasible approach with maintenance therapy for stage 4B epithelial ovarian cancer.

Effectiveness and safety of standard chemotherapy in older patients with ovarian cancer: a retrospective analysis by age group and treatment regimen.

To evaluate the effectiveness and safety of standard chemotherapy administered to patients >70 years with advanced ovarian cancer (OC). Medical records of 956 advanced-stage patients with OC treated between 2002-2020 with standard surgery and paclitaxel-carboplatin chemotherapy in a three-weekly (PC-3W) or weekly (PC-1W) regimen were reviewed. Treatment response and tolerability were compared between patients ≤70 years (N=723) and >70 years (N=233) with stratification to septuagenarians (>70-80 years) and octogenarians (>80 years). Median overall survival (mOS) in patients >70 was 41.26 months (95% confidence interval [Cl], 37.22-45.14) and median progression-free survival (mPFS) was 11.04 months (95% Cl, 8.97-15.74). No statistically significant differences in mPFS and mOS were observed between septuagenarians and octogenarians. Patients >70 treated with PC-1W versus PC-3W had significantly longer mOS (57.17 versus 30.00 months) and mPFS (19.09 versus 8.15 months). Toxicity rates were mostly similar between younger and older patients. Among patients >70 treated with PC-1W, the rate of neutropenia (75.7% versus 51.8%, p=0.0005), thrombocytopenia (41.0% versus 22.2%, p=0.0042) and anemia (78.1% versus 51.9%, p<0.0001) were significantly higher and the rate of grade 2 alopecia was statistically significantly lower compared with those >70 treated with PC-3W. Significantly more patients treated with PC-1W completed ≥6 chemotherapy cycles, suggesting better tolerability of this regimen. Older patients with OC may benefit from improved OS with reasonable toxicity if treated with standard chemotherapy. Older patients treated with PC-1W are more likely to complete the full chemotherapy course and survive longer compared with those treated with conventional PC-3W.

Hematological Side Effects Management of Paclitaxel - Carboplatin Chemotherapy in Lung Cancer

Background: Paclitaxel-carboplatin chemotherapy can cause hema-tological disorders. This regiment's hematological side effects include anemia, neutropenia, and thrombocytopenia. Data showed this regiment side effect occurs with grade iii/iv toxicity anemia, grade III/IV anemia by 41%, neutropenia (78%), and thrombocytopenia (41%). This hema-tological disorder occurs in bone marrow-producing areas due to chemotherapy. Each hematological disorder requires separate interven-tion.Case Presentation: A 54-year-old woman was diagnosed with a progressive disease of left lung adenocarcinoma (Exon 21 mutation) with TKI and received paclitaxel-carboplatin chemotherapy. The patient experienced side effects of anemia, neutropenia, and thrombocytopenia. Anemia was treated with PRC transfusion, neutropenia corrected with Filgrastim, and thrombocytopenia with platelet transfusion. Chemo-therapy was discontinued after five cycles because the Thrombo-cytopenia condition did not improve.Conclusion: Hematological parameters are essential in preparing for lung cancer chemotherapy. Uncorrectable hematological disorders lead to discontinuation of chemotherapy

57P A study of gemcitabine-cisplatin vs paclitaxel-carboplatin chemotherapy in patients with advanced squamous cell carcinoma of the lung

57P A study of gemcitabine-cisplatin vs paclitaxel-carboplatin chemotherapy in patients with advanced squamous cell carcinoma of the lung

Efficacy of oral ferric citrate hydrate treatment for anemia caused by niraparib: a case report

BackgroundMaintenance therapy using poly(adenosine diphosphate-ribose)polymerase inhibitors may have adverse events, including hematological toxicity, and may limit therapeutic potential in patients with cancer. Niraparib-induced anemia negatively impacts one’s quality of life. Its amelioration by ferrous iron (for example, sodium ferrous citrate), folic acid, or vitamin B12 has not been supported. Oral ferric citrate hydrate increases circulating levels of iron and hepatic iron accumulation, improving renal anemia in patients with kidney failure receiving hemodialysis. The uptake of ferric iron is considered to be much higher than that of ferrous iron.Case presentationThe admitted patient was a 57-year-old Japanese woman with stage IIIB ovarian cancer who underwent primary debulking surgery and standard carboplatin–paclitaxel chemotherapy combined with bevacizumab, followed by niraparib (200 mg/day) maintenance therapy. The patient started oral SFC (100 mg/day) to treat niraparib-related anemia. However, she required two units of packed red blood cell transfusions three times within 3 months after starting niraparib treatment. The patient was diagnosed with niraparib-related anemia. The blood test results after 1 month from the start of niraparib treatment were as follows: red blood cells, 211 × 104/μL; hemoglobin, 7.0 g/dL; hematocrit, 20.8%; reticulocyte, 0.2%; platelet count, 18.0 × 104/μL. She was switched to oral ferric citrate hydrate with a dose of 500 mg per day and resumed niraparib treatment. She did not experience grade 3 niraparib-related hematological toxicity and achieved blood transfusion independence.ConclusionsFerric citrate hydrate may be a safe, effective, and well-tolerated oral drug for treating patients with niraparib-related anemia.

Neoadjuvant Chemotherapy in Stadium IB3, IIA2 and IIB Cervical Cancer a Narrative Review

This study aimed to describe Paclitaxel-Carboplatin chemotherapy as neoadjuvant chemotherapy in stage IB3, IIA2 and IIB cervical cancer. The review was conducted by collecting journals from previous studies discussing neoadjuvant chemotherapy in cervical cancer stages IB3, IIA2, and IIB and in this case specifically discussing Paclitaxel-Carboplatin chemotherapy. Neoadjuvant chemotherapy refers to systemic therapy intended to reduce the size of the tumour before the definitive operation. Several studies have shown that neoadjuvant chemotherapy has greater advantages than surgery alone for early stage cancers (IB3, IIA2, and IIB). Paclitaxel and Carboplatin are known chemotherapeutic agents that can be used as neoadjuvant chemotherapy. Neoadjuvant Chemotherapy regimen Paclitaxel Carboplatin is one of the options in performing therapy for early stage cervical cancer which can be very helpful in healing and cancer-free patient condition. Neoadjuvant chemotherapy followed by radical surgery has significant benefits that have been described in several previous studies. Neoadjuvant Chemotherapy regimen Paclitaxel Carboplatin may be used as therapy regimen for early stage cervical cancer with all advantage compared to only surgery. Thus, this type of regimen can be used to decrease mortality and morbidity in patient with stadium IB3, IIA2 and IIB cervical cancer.

KEYNOTE-C93/GOG-3064/ENGOT-en15: A phase 3, randomized, open-label study of first-line pembrolizumab versus platinum-doublet chemotherapy in mismatch repair deficient advanced or recurrent endometrial carcinoma.

TPS5623 Background: Carboplatin-paclitaxel chemotherapy (with trastuzumab for HER2+ uterine serous carcinoma) is the standard of care first-line systemic treatment for recurrent or metastatic endometrial carcinoma (EC), which has a 5-year relative survival rate of only 17%. Worse survival outcomes have been shown for the mismatch repair deficient (dMMR) subtype of EC. Pembrolizumab (pembro), an anti-PD-1 antibody, showed compelling antitumor activity in previously treated, advanced MSI-H/dMMR EC in the phase 2 KEYNOTE-158 study (ORR, 48%; median duration of response [DOR], not reached; O’Malley JCO 2022). KEYNOTE-C93/GOG-3064/ENGOT-en15 (NCT05173987) is a phase 3, randomized, open-label study evaluating first-line pembro versus carboplatin-paclitaxel chemotherapy in patients with dMMR advanced or recurrent EC. Methods: Patients aged ≥18 years with histologically confirmed stage III/IV recurrent EC including carcinosarcoma (mixed Mullerian tumor), radiographically evaluable disease (measurable or nonmeasurable per RECIST v1.1), no prior systemic therapy (prior radiation with or without radiosensitizing chemotherapy &gt; 2 weeks before first dose or prior hormonal therapy ≥1 week before randomization is permitted), and an ECOG PS ≤1 are eligible. Patients must have central confirmation of dMMR status. Approximately 350 patients will be randomized 1:1 to receive pembro 400 mg IV Q6W for 18 cycles (̃2 years) or carboplatin AUC 5 or 6 mg/mL/min IV Q3W and paclitaxel 175 mg/m2 IV Q3W for 6 cycles (with option for &gt; 6 cycles). Trastuzumab is permitted for patients in the chemotherapy arm with HER2+ serous EC. Randomization is stratified by disease status (newly diagnosed advanced EC vs recurrent EC) and histology (endometrioid vs nonendometrioid). Treatment will continue for the specified number of cycles or until PD or unacceptable toxicity. Patients in the chemotherapy arm have the option to receive pembro following confirmed PD by blinded independent central review (BICR). Tumor imaging will be performed Q9W from randomization to week 54 and Q12W thereafter. AEs will be assessed from randomization to 30 days (90 days for serious AEs) after treatment discontinuation and graded per NCI CTCAE version 5.0. Dual primary endpoints are PFS per RECIST v1.1 by BICR and OS. Secondary endpoints are ORR, disease control rate, and DOR per RECIST v1.1 by BICR; PFS per RECIST v1.1 by investigator review; PFS2 (ie, time from randomization to PD per investigator assessment or death from any cause after start of subsequent anticancer therapy); safety; and patient-reported outcomes. PFS and OS will be estimated by the Kaplan-Meier method, with treatment differences assessed by the stratified log-rank test and HRs with 95% CIs determined using a Cox proportional hazard model. Enrollment is ongoing. Clinical trial information: NCT05173987.

Clinicopathologic and molecular features associated with response to anti-HER2 therapy in endometrial cancer.

5584 Background: Endometrial cancer (EC) is the most common gynecologic malignancy in the United States. Human epidermal growth factor 2 (HER2) overexpression or gene amplification occurs in 10-60% of EC. The addition of trastuzumab to carboplatin-paclitaxel chemotherapy improves survival in women with HER2-positive serous EC. However, criteria for assessment of HER2 status in EC are not standardized, and furthermore, intratumor heterogeneity may impact therapeutic efficacy. We aimed to identify factors associated with treatment response and survival outcomes in a retrospective cohort of ECs treated with anti-HER2 therapy. Methods: Patients with advanced/recurrent EC treated with trastuzumab or trastuzumab emtansine alone or in combination with chemotherapy from 2013-2021 at our institution were identified. Clinical and treatment information were retrieved from medical records. Central pathology review, HER2 immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) were performed. HER2 IHC was scored using modified ASCO/CAP 2007 guidelines for breast cancer. HER2 expression heterogeneity was defined as a 2-degree difference in staining intensity in ≥5% of tumor cells or discordant IHC score on different specimens. HER2 amplification (tumor/normal fold change) was also estimated from targeted next-generation sequencing (NGS). Best response was assessed by RECIST v1.1 as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), with clinical benefit defined as CR/PR/SD. Results: Among 39 patients included, median age was 69. Histologic subtypes included serous (n = 18, 46%), carcinosarcoma (n = 7, 18%), high-grade EC with ambiguous features (n = 13, 33%) and low-grade endometrioid carcinoma (n = 1, 3%). HER2 IHC results were 0 or 1+ (n = 2, 5%), 2+ (n = 17, 46%), 3+ (n = 18, 49%), with HER2 heterogeneity in 15 cases. By FISH, the HER2/CEP17 ratio was ≥2.0 in 34 (92%) and &lt; 2.0 in 3 (8%); HER2 copy number (CN) was ≥6.0 in 25 (68%) and &lt; 6.0 in 12 (32%). HER2 copy number ≥6.0 was significantly correlated with HER2 amplification by NGS ( p&lt; 0.001). 18 (49%) patients had a co-existing somatic PIK3CA mutation. Amongst parameters assessed, only higher level of HER2 amplification by NGS was significantly associated with clinical benefit ( p= 0.036). None of these features were associated with progression-free survival. Notably, 2 patients with IHC 0/1+ had PD and 1 patient with IHC 3+, but non-amplified by FISH, achieved PR. Conclusions: In our cohort of EC patients treated with anti-HER2 therapy, higher level of HER2 amplification was associated with clinical benefit. Further studies with larger sample sizes are needed to determine whether any additional characteristics are associated with treatment response and survival.

Pharmacological ascorbate improves the response to platinum-based chemotherapy in advanced stage non-small cell lung cancer

PurposePlatinum-based chemotherapy with or without immunotherapy is the mainstay of treatment for advanced stage non-small cell lung cancer (NSCLC) lacking a molecular driver alteration. Pre-clinical studies have reported that pharmacological ascorbate (P-AscH-) enhances NSCLC response to platinum-based therapy. We conducted a phase II clinical trial combining P-AscH- with carboplatin-paclitaxel chemotherapy. Experimental designChemotherapy naïve advanced stage NSCLC patients received 75 g ascorbate twice per week intravenously with carboplatin and paclitaxel every three weeks for four cycles. The primary endpoint was to improve tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 compared to the historical control of 20%. The trial was conducted as an optimal Simon's two-stage design. Blood samples were collected for exploratory analyses. ResultsThe study enrolled 38 patients and met its primary endpoint with an objective response rate of 34.2% (p = 0.03). All were confirmed partial responses (cPR). The disease control rate was 84.2% (stable disease + cPR). Median progression-free and overall survival were 5.7 months and 12.8 months, respectively. Treatment-related adverse events (TRAE) included one grade 5 (neutropenic fever) and five grade 4 events (cytopenias). Cytokine and chemokine data suggest that the combination elicits an immune response. Immunophenotyping of peripheral blood mononuclear cells demonstrated an increase in effector CD8 T-cells in patients with a progression-free survival (PFS) ≥ 6 months. ConclusionsThe addition of P-AscH- to platinum-based chemotherapy improved tumor response in advanced stage NSCLC. P-AscH- appears to alter the host immune response and needs further investigation as a potential adjuvant to immunotherapy.

Deep Infiltrating Endometriosis Malignant Invasion of Cervical Wall and Rectal Wall With Lynch Syndrome： A Rare Case Report and Review of Literature.

BackgroundMalignant transformation of deep infiltrating endometriosis (DIE) invading the cervix and rectum is quite rare, especially in patients combined with Lynch syndrome (LS). We report a rare case of a 49-year-old perimenopausal woman with endometrioid carcinoma arising from the pouch of Douglas, invading the cervix and rectum 1 year after a unilateral salpingo-oophorectomy treatment for ovarian endometriosis. The genetic testing of the patient showed germline mutations in MSH2, which combined with the special family history of colorectal cancer of the patient, was also thought to be associated with LS. We have analyzed the reported cases of DIE malignant transformation over the last 10 years, and reviewed the relevant literature, in order to strengthen the clinical management of patients with endometriosis, particularly patients with DIE, and reveal a possible correlation between malignant transformation of endometriosis and LS.Case PresentationA 49-year-old perimenopausal woman presented with hypogastralgia, diarrhea, and intermittent fever for more than 1 month. A Transvaginal ultrasound (TVS) showed a cervix isthmus mass, and a magnetic resonance imaging (MRI) showed a mass in pouch of Douglas with high suspicion of malignancy, possibly invading the anterior wall of the rectum. Prior to surgery, the patient performed the ultrasound guided pelvic mass biopsy through the vagina, and the pathology of the mass showed endometrioid carcinoma. The patient received a gynecological–surgical laparotomy and enterostomy, and a histopathology revealed endometrioid carcinoma infiltrating the cervical wall and rectal wall. In the family genetic history of the patient, her mother and two sisters suffered from colorectal cancer, so lesion tissue and blood were taken for genetic testing, which showed a germline mutation in MSH2, with LS being considered. After the surgical treatment, the patient received six courses of paclitaxel–carboplatin chemotherapy. During the course of treatment, bone marrow suppression occurred, but was healed after symptomatic treatment. To date, the patient is generally in good health, and imaging examination showed no evidence of recurrence.ConclusionThe risk of malignant transformation of endometriosis is increased in perimenopause and postmenopause, as DIE is a rare malignant transformation of endometriosis. DIE can invade other adjacent organs and cause poor prognosis, thus, comprehensive gynecological–surgical treatment should be necessary. In addition, if histopathology showed endometrioid carcinoma, the possibility of LS should be considered, and if necessary, immunohistochemical staining and gene detection should be improved to provide follow-up targeted therapy and immunotherapy.

IOLite: phase 1b trial of doublet/triplet combinations of dostarlimab with niraparib, carboplatin–paclitaxel, with or without bevacizumab in patients with advanced cancer

BackgroundDoublet combination therapies targeting immune checkpoints have shown promising efficacy in patients with advanced solid tumors, but it is unknown if rational triplet combinations will be well tolerated and associated...

Genomic Instability Is Defined by Specific Tumor Microenvironment in Ovarian Cancer: A Subgroup Analysis of AGO OVAR 12 Trial.

Simple SummaryGiven the importance of genomic instability signatures in the management of ovarian cancer and the difficulties in defining the role of immunotherapy, our objective was to describe the tumor immune microenvironment in the light of genomic instability signatures. Intratumoral CD3+ T lymphocytes confirmed its prognostic value. HLA-E appears to be a robust prognostic biomarker and preferentially overexpressed in homologous recombination deficiency (HRD) ovarian cancers. Our data provide a rationale for future immunotherapy strategies targeting the inhibitory CD94/NKG2A receptor of HLA-E in HRD tumors.Background: Following disappointing results with PD-1/PD-L1 inhibitors in ovarian cancer, it is essential to explore other immune targets. The aim of this study is to describe the tumor immune microenvironment (TME) according to genomic instability in high grade serous ovarian carcinoma (HGSOC) patients receiving primary debulking surgery followed by carboplatin-paclitaxel chemotherapy +/− nintedanib. Methods: 103 HGSOC patients’ tumor samples from phase III AGO-OVAR-12 were analyzed. A comprehensive analysis of the TME was performed by immunohistochemistry on tissue microarray. Comparative genomic hybridization was carried out to evaluate genomic instability signatures through homologous recombination deficiency (HRD) score, genomic index, and somatic copy number alterations. The relationship between genomic instability and TME was explored. Results: Patients with high intratumoral CD3+ T lymphocytes had longer progression-free survival (32 vs. 19.6 months, p = 0.009) and overall survival (OS) (median not reached). High HLA-E expression on tumor cells was associated with a longer OS (median OS not reached vs. 52.9 months, p = 0.002). HRD profile was associated with high HLA-E expression on tumor cells and an improved OS. In the multivariate analysis, residual tumor, intratumoral CD3, and HLA-E on tumor cells were more predictive than other parameters. Conclusions: Our results suggest HLA-E/CD94-NKG2A/2C is a potential immune target particularly in the HRD positive ovarian carcinoma subgroup.

A Rare Case of Squamous Cell Carcinoma Arising in Mature Cystic Teratoma

BACKGROUND: Mature cystic teratoma (MCT) is a common benign adnexal tumor contributing to about 20% of all ovarian tumors, and it may occur in 10–20% of women during their lifetime. Although the nature of MCT of the ovary is benign, about 1–2% of MCT undergo malignant transformation. CASE REPORT: Here, we report a rare case of squamous cell carcinoma (SCC) arising in MCT. This one rare case report of SCC arising in MCT showed satisfactory response to adjuvant chemotherapy. Careful routine evaluation is needed for possible recurrency. CONCLUSION: This patient was found with infiltration to the urinary bladder and concluded as stage IIB; therefore, the surgeon decided to give adjuvant chemotherapy with paclitaxel/carboplatin. After given three cycles of paclitaxel carboplatin chemotherapy the patient showed favorable outcome, as the CT scan evaluation showed no residual mass.

356 Personalized immunotherapy by adoptive T cell transfer during chemotherapy with or without interferon-alpha in patients with recurrent platinum-sensitive epithelial ovarian cancer

BackgroundEpithelial ovarian cancer (EOC) is considered an immunogenic tumor, as illustrated by the clear correlation between T-cell infiltration and overall survival. This suggests that patients with EOC may be eligible for immunotherapy including adoptive cell therapy with autologous Tumor Infiltrating Lymphocytes (TIL). However, immunosuppressive cells including myeloid derived suppressor cells an regulatory T cells are also abundant in EOC and may need to be targeted simultaneously to achieve the full potential of the infused TIL. Carboplatin-paclitaxel chemotherapy (CPC) reduces the number of immunosuppressive cells in cervical cancer patients,1 creating a window-of-opportunity for TIL to exert their full effector function. Interferon-alpha further supports infused TIL. A phase I/II trial (NCT04072263) was initiated to study the feasibility and safety of TIL during CPC with or without additional interferon-alpha in patients with recurrent platinum-sensitive EOC.MethodsFifteen patients with recurrent platinum-sensitive EOC received 6 cycles of CPC intravenously every 3 weeks and TIL intravenously 2 weeks after the 2nd,3rd and 4th CPC cycle. Pegylated-interferon-alpha was added in the second cohort for 12 weeks, starting one week before the first TIL infusion. Patients who received 3 TIL infusions were evaluable. The primary endpoint was feasibility and safety of TIL administration during CPC with or without interferon-alpha. As secondary endpoints signs of activity, underlying mechanisms, immunomodulation, and T-cell reactivity were studied.ResultsThirteen patients were available for analysis. Median age 63 years (range, 29–77). TIL could be successfully expanded for all patients. Treatment with TIL during CPC was safe and did not add toxicity. Addition of IFNα resulted in grade 3 leucopenia and grade 3 trombocytopenia in the first 2 patients and was therefore omitted in subsequent patients. CPC alleviated the immunosuppressive status, reflected by reduced plasma IL-6 levels and circulating myeloid-cell numbers, while lymphocytes numbers are not affected. This was most prominently at 1–2 weeks after the 2nd CPC and is suggested to reflect improved conditions promoting intra-tumoral T-cell reactivity. Objective responses were observed in 10/13 (77%) patients and 3 patients had stable disease. Interestingly, in at least one patient the ongoing platinum-free interval of 25 months far exceeds the first platinum-free interval of 8 months after similar CPC. In depth studies on immune modulation by chemotherapy and by TIL/Interferon-alpha, and correlations between TIL phenotype and clinical outcome are ongoing and will be presented.ConclusionsCombined treatment with CP chemotherapy and properly timed TIL may result in clinical benefit for patients with EOC.AcknowledgementsThe unrestricted funding of the trial by Ovacure is greatly acknowledged.Trial RegistrationThe trial is registered at www.clinicaltrials.gov under number NCT04072263.ReferenceWelters MJ, van der Sluis TC, van Meir H, Loof NM, van Ham VJ, van Duikeren S, Santegoets SJ, Arens R, de Kam ML, Cohen AF, van Poelgeest MI, Kenter GG, Kroep JR, Burggraaf J, Melief CJ, van der Burg SH. Vaccination during myeloid cell depletion by cancer chemotherapy fosters robust T cell responses. Sci Transl Med 2016;8(334):334ra52. doi: 10.1126/scitranslmed.aad8307Ethics ApprovalThis study was approved by Leiden University Medical Center‘s Ethics Board; approval number L18-012 and the Central Committee on Research Involving Human Subjects; approval number NL63434.000.17.

Preferential HER2 Expression in Lymphovascular Invasion of a Uterine Carcinosarcoma, a Case Report

Abstract Introduction/Objective Uterine carcinosarcoma (UCS) is a rare, highly aggressive cancer accounting for &amp;lt;5% of reported uterine cancer cases. Commonly, myometrial invasion and lymphovascular invasion (LVI) are found at diagnosis, and recurrence rates of &amp;gt;40% are seen after therapy accounting for poor prognosis and high rate (16%) of death. Histologically, it is composed of both carcinoma and sarcoma components. HER2-targeted therapy without adjunctive chemotherapy for the treatment of UCS has generally not shown beneficial clinical responses, but a more recent phase II clinical trial revealed that the addition of Trastuzumab, a HER2-targeted monoclonal antibody, to carboplatin-paclitaxel chemotherapy showed an increase in progression free survival. Methods/Case Report Immunohistochemical (IHC) staining for HER2 was performed on histologic sections of UCS, areas of LVI, and lymph node metastasis (LNM). Confirmatory HER2 fluorescent in situ hybridization (FISH) studies were performed on the primary UCS and the LVI portion. A 67-year-old female presented with postmenopausal uterine bleeding. CT showed an enlarged uterus, widened endometrial canal, and enlarged lymph nodes. Initial endometrial biopsy showed UCS. Exploratory laparotomy with total abdominal hysterectomy, bilateral salpingo-ophorectomy, omentectomy, and lymph node dissection was performed with pathology confirming UCS with 86% myometrial invasion and LVI. Results (if a Case Study enter NA) NA Conclusion HER2 expression in this patient was solely seen in foci of LVI and within LNM. This finding suggests inclusion of histologic sections with LVI and LNM when evaluating for the presence of HER2 expression in uterine carcinosarcoma with reflex FISH testing when indicated may be helpful to provide additional treatment opportunities for patients. Further studies need to be performed to determine if this finding in generalizable to carcinosarcoma and endometrial serous carcinoma samples.

Results of TRIO-14, a phase II, multicenter, randomized, placebo-controlled trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-ganitumab in newly diagnosed epithelial ovarian cancer

PurposeInsulin-like growth factor (IGF) signaling is implicated in pathogenesis and chemotherapy resistance of epithelial ovarian cancer (EOC). We explored efficacy and safety of adding ganitumab, a monoclonal antibody targeting IGF-1R, to carboplatin/paclitaxel (CP) chemotherapy in patients with primary EOC. DesignPatients were randomly assigned to receive CP/ganitumab (18 mg/kg q3w) or CP/placebo for 6 cycles followed by 6 cycles of single agent ganitumab/placebo maintenance therapy as front-line therapy. Primary endpoint was progression free survival. Secondary endpoints were time to progression and overall survival. Pretreatment samples were prospectively collected for retrospective biomarker analyses. Results170 patients enrolled. 165 patients assessable for toxicity. Median PFS was 15.7 months with CP/ganitumab and 16.7 months with CP/placebo (HR 1.23; 95% CI 0.82–1.83, P = 0.313). All grade neutropenia (84.1% vs 71.4%), thrombocytopenia (75.3% vs 57.1%) and hyperglycemia (15.9% vs 2.6%) were more common in the ganitumab group compared to the placebo group. Ganitumab/placebo related serious adverse events were reported in 26.1% of the patients with ganitumab and in 6.5% with placebo. Non-progression related fatal events were more common with ganitumab (5 versus 2 patients). The ganitumab group experienced more dose delays which resulted in lower relative dose intensity of chemotherapy in the experimental group. In an exploratory model IGFBP2 expression was predictive of ganitumab response (treatment interaction; PFS, P = 0.03; OS, P = 0.01). ConclusionAddition of ganitumab to CP chemotherapy in primary EOC did not improve PFS. Our results do not support further study of ganitumab in unselected EOC patients.

729P Adoptive T-cell therapy during chemotherapy with or without peginterferon-α (IFNα) in patients with platinum sensitive recurrent epithelial ovarian cancer (EOC)

The correlation between T-cell infiltration and EOC survival suggests that EOC may be sensitive to adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL). Carboplatin-paclitaxel chemotherapy (CPC) lowers the number of tumor induced immune suppressive myeloid cells, creating a window-of-opportunity for TILs to exert their effective anti-tumor response. IFNα supports TIL. A phase I/II trial (NCT04072263) was initiated to study the feasibility and safety of TIL during CPC +/- IFNα in patients with recurrent platinum sensitive EOC.