Platinum Combination Research Articles

Patterns of chemotherapy use in women with recurrent endometrial cancer (582)

Objectives: Recurrent endometrial cancer has a poor prognosis. The optimal treatment regimen in this setting remains unclear. The objective of this study was to describe patterns of utilization of cytotoxic, hormonal, and immunotherapy in women with endometrial cancer in the adjuvant setting and at the time of the first recurrence. Methods: A retrospective cohort study using the IBM MarketScan database was performed. We identified commercially insured women with endometrial cancer who underwent hysterectomy between 2011 and 2019, with or without adjuvant treatment. The use of clinically relevant therapeutic agents and those that were utilized in >2% of the cohort, as well as combination regimens, were determined in the adjuvant setting and at the time of the first recurrence. Recurrence was defined based on the introduction of a new agent or a gap of greater than three months from adjuvant therapy, or based on the initiation of chemotherapy more than 180 days after hysterectomy, for patients who did and did not receive adjuvant chemotherapy, respectively. Results: A total of 21,327 patients were identified. Of these, 6,828 (32.0%) received adjuvant radiation therapy, and 4,189 (19.6%) received adjuvant chemotherapy (78.2% of whom also received radiation). Of those who received adjuvant chemotherapy, the most commonly utilized agents were carboplatin (90.5%), paclitaxel (85.8%), cisplatin (9.4%), docetaxel (9.3%), gemcitabine (3.8%), and doxorubicin (2.1%), while bevacizumab was utilized in 1.5% of patients. A combination of platinum and a taxane was utilized as adjuvant therapy in 88.9% of women. Therapy for recurrent endometrial cancer was initiated in 1,707 patients (8.0% of the entire cohort). The median time from hysterectomy to initiation of chemotherapy for recurrence was 13.3 months (IQR: 7.6 to 23.0 months). Overall, platinum and taxane combination therapy was used in 747 (49.2%) patients, platinum alone or with other drugs in 186 (12.2%), and taxanes alone or with other drugs in 135 (8.9%). Non-platinum/non- taxane cytotoxic therapy was started in 236 (15.5%) patients, while 130 (8.6%) were treated with hormonal therapy and 24 (1.6%) with immunotherapy. While most patients who had not received adjuvant therapy also received platinum-based therapy, they were more likely than those who received adjuvant therapy to receive non-platinum- based regimens and hormonal therapy. Conclusions: Among women with endometrial cancer who underwent a hysterectomy, platinum-taxane combination chemotherapy was used in almost 90% of patients as adjuvant therapy while nearly 70% of women were treated with platinum or taxane-based therapy at first recurrence. Objectives: Recurrent endometrial cancer has a poor prognosis. The optimal treatment regimen in this setting remains unclear. The objective of this study was to describe patterns of utilization of cytotoxic, hormonal, and immunotherapy in women with endometrial cancer in the adjuvant setting and at the time of the first recurrence. Methods: A retrospective cohort study using the IBM MarketScan database was performed. We identified commercially insured women with endometrial cancer who underwent hysterectomy between 2011 and 2019, with or without adjuvant treatment. The use of clinically relevant therapeutic agents and those that were utilized in >2% of the cohort, as well as combination regimens, were determined in the adjuvant setting and at the time of the first recurrence. Recurrence was defined based on the introduction of a new agent or a gap of greater than three months from adjuvant therapy, or based on the initiation of chemotherapy more than 180 days after hysterectomy, for patients who did and did not receive adjuvant chemotherapy, respectively. Results: A total of 21,327 patients were identified. Of these, 6,828 (32.0%) received adjuvant radiation therapy, and 4,189 (19.6%) received adjuvant chemotherapy (78.2% of whom also received radiation). Of those who received adjuvant chemotherapy, the most commonly utilized agents were carboplatin (90.5%), paclitaxel (85.8%), cisplatin (9.4%), docetaxel (9.3%), gemcitabine (3.8%), and doxorubicin (2.1%), while bevacizumab was utilized in 1.5% of patients. A combination of platinum and a taxane was utilized as adjuvant therapy in 88.9% of women. Therapy for recurrent endometrial cancer was initiated in 1,707 patients (8.0% of the entire cohort). The median time from hysterectomy to initiation of chemotherapy for recurrence was 13.3 months (IQR: 7.6 to 23.0 months). Overall, platinum and taxane combination therapy was used in 747 (49.2%) patients, platinum alone or with other drugs in 186 (12.2%), and taxanes alone or with other drugs in 135 (8.9%). Non-platinum/non- taxane cytotoxic therapy was started in 236 (15.5%) patients, while 130 (8.6%) were treated with hormonal therapy and 24 (1.6%) with immunotherapy. While most patients who had not received adjuvant therapy also received platinum-based therapy, they were more likely than those who received adjuvant therapy to receive non-platinum- based regimens and hormonal therapy. Conclusions: Among women with endometrial cancer who underwent a hysterectomy, platinum-taxane combination chemotherapy was used in almost 90% of patients as adjuvant therapy while nearly 70% of women were treated with platinum or taxane-based therapy at first recurrence.

Upregulation of the Long Noncoding RNA CASC10 Promotes Cisplatin Resistance in High-Grade Serous Ovarian Cancer.

Despite initial responses to first-line treatment with platinum and taxane-based combination chemotherapy, most high-grade serous ovarian carcinoma (HGSOC) patients will relapse and eventually develop a cisplatin-resistant fatal disease. Due to the lethality of this disease, there is an urgent need to develop improved targeted therapies against HGSOC. Herein, we identified CASC10, a long noncoding RNA upregulated in cisplatin-resistant ovarian cancer cells and ovarian cancer patients. We performed RNA sequencing (RNA-seq) in total RNA isolated from the HGSOC cell lines OVCAR3 and OV-90 and their cisplatin-resistant counterparts. Thousands of RNA transcripts were differentially abundant in cisplatin-sensitive vs. cisplatin-resistant HGSOC cells. Further data filtering unveiled CASC10 as one of the top RNA transcripts significantly increased in cisplatin-resistant compared with cisplatin-sensitive cells. Thus, we focused our studies on CASC10, a gene not previously studied in ovarian cancer. SiRNA-mediated CASC10 knockdown significantly reduced cell proliferation and invasion; and sensitized cells to cisplatin treatment. SiRNA-mediated CASC10 knockdown also induced apoptosis, cell cycle arrest, and altered the expression of several CASC10 downstream effectors. Multiple injections of liposomal CASC10-siRNA reduced tumor growth and metastasis in an ovarian cancer mouse model. Our results demonstrated that CASC10 levels mediate the susceptibility of HGSOC cells to cisplatin treatment. Thus, combining siRNA-mediated CASC10 knockdown with cisplatin may represent a plausible therapeutic strategy against HGSOC.

Taxane monotherapy regimens for the treatment of recurrent epithelial ovarian cancer.

Taxane monotherapy regimens for the treatment of recurrent epithelial ovarian cancer.

MO43-5 Cost analysis of multiple drug chemotherapy for advanced gastric cancer

Chemotherapy for unresectable advanced gastric cancer is standardized as a combination of platinum and pyrimidine fluoride anticancer drugs. Currently, multiple regimens are available; however, the drug costs and side effects differ and the distribution of costs per regimen is unclear. We verified the resources used by aggregating medical receipts for patients with gastric cancer receiving chemotherapy using NDB.

PSY1-2 Combined immunotherapy for non-small cell lung cancer

First-line treatment of non-small cell lung cancer (NSCLC) has undergone a paradigm shift to platinum combination chemotherapy together with an immune checkpoint inhibitor. In addition, such chemotherapy plus nivolumab (antibody to PD-1) and ipilimumab (antibody to cytotoxic T lymphocyte-associated protein-4) prolonged survival in advanced NSCLC patients compared with chemotherapy alone. It is expected as a treatment aiming for long-term survival. The differences in the positioning of immunotherapy for NSCLC from other cancer types are as follows: (1) In patients with positive driver gene alteration such as EGFR gene mutation or ALK translocation, anti-PD-(L)1 antibody alone is ineffective, and (2) The positioning of anti-CTLA-4 antibody has not yet been determined.

Cell-Free Tumor DNA Dominant Clone Allele Frequency Is Associated With Poor Outcomes in Advanced Biliary Cancers Treated With Platinum-Based Chemotherapy.

This investigation sought to evaluate the prognostic value of pretreatment of circulating tumor DNA (ctDNA) in metastatic biliary tract cancers (BTCs) treated with platinum-based first-line chemotherapy treatment. We performed a retrospective analysis of 67 patients who underwent ctDNA testing before platinum-based chemotherapy for first-line treatment for metastatic BTC. For analysis, we considered the detected gene with highest variant allele frequency as the dominant clone allele frequency (DCAF). Results of ctDNA analysis were correlated with patients' demographics, progression-free survival (PFS), and overall survival (OS). The median age of patients was 67 (27-90) years. Fifty-four (80.6%) of 67 patients evaluated had intrahepatic cholangiocarcinoma; seven had extrahepatic cholangiocarcinoma, and six gallbladder cancers. Forty-six (68.6%) of the patients were treated with cisplatin plus gemcitabine, and 16.4% of patients received gemcitabine and other platinum (carboplatin or oxaliplatin) combinations, whereas 15% of patients were treated on a clinical trial with gemcitabine and cisplatin plus additional agents (CX4945, PEGPH20, or nab-paclitaxel). TP53, KRAS, FGFR2, ARID1A, STK11, and IDH1 were the genes with highest frequency as DCAF. The median DCAF was 3% (0%-97%). DCAF > 3% was associated with worse OS (median OS: 10.8 v 18.8 months, P = .032). Stratifying DCAF in quartiles, DCAF > 10% was significantly related to worse PFS (median PFS: 3 months, P = .014) and worse OS (median OS: 7.0 months, P = .001). Each 1% increase in ctDNA was associated with a hazard ratio of 13.1 in OS when adjusting for subtypes, metastatic sites, size of largest tumor, age, sex, and CA19-9. DCAF at diagnosis of advanced BTC can stratify patients who have worse outcomes when treated with upfront platinum-based chemotherapy. Each increase in %ctDNA decreases survival probabilities.

P-72 Real-world treatments and outcomes for biliary tract cancer patients using administrative databases in Ontario, Canada

There is a paucity of literature on treatment patterns and outcomes in biliary tract cancer (BTC) patients in Canada. The aim of this study was to better understand treatment patterns and survival outcomes of BTC patients in Ontario. We conducted a retrospective population-level study in Ontario using ICES datasets on patients diagnosed with de novo or recurrent, advanced BTC (including: gallbladder cancer, intrahepatic and extrahepatic cholangiocarcinoma [IHC and EHC, respectively], Ampulla of Vater [AoV]) between January 1, 2010 and December 31, 2019. Follow-up data were available until December 31, 2020. Patients were categorized as de novo if they had stage IV disease at the time of first diagnosis, and as recurrent if they had a prior diagnosis of early stage (I-III) or unknown/missing (UNK/M) disease and received a BTC treatment (proxy for progression). Patients were excluded if they died before BTC diagnosis or had a prior cancer diagnosis. To determine the longitudinal trajectory of care for BTC patients, linkages were made between 8 national/provincial data sets. A total of 2,666 advanced BTC patients were identified, of which 471 (17.7%) were gallbladder, 785 (29.4%) were IHC, 864 (32.4%) were EHC, 304 (11.4%) were AoV and 242 (9.1%) had an unspecified BTC diagnosis. Out of 2,666, 828 (31.1%) were diagnosed with de novo and 1,838 (68.9%) were diagnosed with recurrent disease. The median age at diagnosis was 67 (interquartile range [IQR] 59-74) that significantly (p<0.001) varied between de novo and recurrent patients, and a majority (50.5%) of the patients were male. A total of 2,307 (86.5%) patients received first-line (1L) treatment. The most common 1L treatments were a platinum and gemcitabine combination – cisplatin and gemcitabine ( gem/cis ) (50.1%) and carboplatin and gemcitabine ( gem/carbo) (4.9%), followed by gemcitabine monotherapy ( gemmono ) (17.5%), and capecitabine- or fluorouracil-based treatments (fluoropyrimidine [ FP ]) (16.5%). For AoV patients, the most common 1L treatment was gemmono (47.6%). Of those treated with 1L treatments, 38.7% received subsequent treatment(s). The most common treatment in second line (2L) was FP (32.1%). Among the 2,307 treated patients, 1,132 (49.1%) of patients received a stenting procedure. The mean (standard error [SE]) and median (IQR) overall survival (OS) for all advanced BTC patients from diagnosis was 28.8 months (0.83) and 13.1 months (5.7-32.0), respectively. Mean and median OS from diagnosis was longer for patients who received a 1L treatment (32.3 months [0.93] and 16.4 months [IQR 7.8-37.0], respectively) versus untreated patients (6.2 months [0.71] and 2.8 months [1.7-5.6], respectively). Mean and median OS from initiation of treatment was 16.7 months [0.71] and 9.2 months (IQR 4.0-18.9), respectively for non-AoV patients who received gem/cis. This is the first comprehensive, Canadian-specific, real-world evidence study of advanced BTC patients. This study showed that 1L treatment options vary between AoV and non-AoV BTC patients, and patients who receive 1L treatment have greater survival than those who do not. The short OS in advanced BTC patients highlight the need for novel and more effective first-line therapies.

Determination of the extraction frequency of green tea leaves by the antioxidant method

Aim. To determine the optimal extraction frequency of green tea leaves with 60 % ethanol by the antioxidant method.Materials and methods. Chun Myn green tea leaves were the object of the study, the raw material was collected in Anhui province (China) from March to April. Dry green tea leaves were standardized according to the European Pharmacopeia 9.0. Spectrophotometry was used to quantify biologically active substances. The antioxidant activity was determined by the potentiometric method. Potentiometric measurements were performed on a HANNA 2550 pH meter (Germany) with a combined platinum EZDO 50 PO electrode (Taiwan). A UV-1000 spectrophotometer (China) was used to measure the optical density.Results and discussion. The total content of phenolic compounds was 9.60 ± 0.17, 1.30 ± 0.03 and 0.12 ± 0.002 %, catechins – 9.20 ± 0.18, 1.20 ± 0.02 and 0.07 ± 0.002 %, flavonoids – 0.27 ± 0.005, 0.04 ± 0.001, 0.005 ± 0.001, hydroxycinnamic acids – 0.49 ± 0.01, 0.07 ± 0.002 and 0.007 ± 0.001 %, dry residue – 10.75 ± 0.11, 1.59 ± 0.02 and 0.15 ± 0.002 %, the antioxidant activity was 474.08 ± 9.48, 67.70 ± 1.35 and 7.01 ± 0.14 mmol-equiv mdry res-1 for the first, second and third extraction, respectively. According to the results obtained, the optimal number of extractions of the raw material with 60 % ethanol was found to be two.Conclusions. The dynamic of extractions of biologically active substances of green tea leaves has been studied by triple extraction of the raw material to find the optimal extraction frequency; for the first time, a method for determining the extraction frequency based on the antioxidant activity of the extracts has been developed and proposed. It has been found that the optimal extraction rate is 2 times. The results obtained will be used in the further production of herbal medicines, dietary supplements, and cosmetic products with a green tea extract.

Adjuvant and first line chemotherapy use for endometrial cancer

ObjectiveThe objective of this study was to describe patterns of utilization of cytotoxic, hormonal, and immunotherapy in patients with endometrial cancer in the adjuvant setting and at the time of first recurrence. MethodsWe identified patients in the IBM MarketScan database with endometrial cancer who underwent hysterectomy from 2011 to 2019. The use of clinically relevant therapeutic agents and combination regimens was determined in the adjuvant setting and at the time of first recurrence. ResultsA total of 22,632 patients were identified. Of these, 7,147 patients (31.6%) received adjuvant radiation and 4,381 (19.4%) received adjuvant chemotherapy following surgery. Of those who received adjuvant chemotherapy, the most commonly utilized agents were carboplatin (90.3%), paclitaxel (85.8%), cisplatin (9.4%), docetaxel (9.3%), gemcitabine (3.8%), and doxorubicin (2.0%), while bevacizumab was utilized in 1.5% of patients. A combination of platinum and a taxane were utilized as adjuvant therapy in 88.8% of women. Of the cohort, 1,825 patients (8.1%) recurred, of whom 1,017 patients had already received adjuvant chemotherapy. The median time from hysterectomy to initiation of chemotherapy for recurrence was 13.3 months (IQR: 7.6–23.1 months). Overall, platinum and taxane combination therapy was used in 788 (46.8%) of patients with recurrent disease, platinum alone or with other drugs in 194 (11.5%), taxanes alone or with other drugs in 145 (8.6%), and non-platinum and non-taxane based therapy in 31.3%. ConclusionsAmong patients with endometrial cancer who underwent hysterectomy, platinum-taxane combination chemotherapy was used in almost 90% of patients who received adjuvant chemotherapy while nearly 70% of patients who recurred were treated with platinum or taxane based therapy at first recurrence.

BAP1 Loss by Immunohistochemistry Predicts Improved Survival to First-Line Platinum and Pemetrexed Chemotherapy for Patients With Pleural Mesothelioma: A Validation Study

IntroductionPleural mesothelioma (PM) is an aggressive malignancy with no identified predictive biomarkers. We assessed whether tumor BAP1 status is a predictive biomarker for survival in patients receiving first-line combination platinum and pemetrexed therapy. MethodsPM cases (n = 114) from Aalborg, Denmark, were stained for BAP1 on tissue microarrays. Demographic, clinical, and survival data were extracted from registries and medical records. Surgical cases were excluded. BAP1 status was associated with overall survival (OS) by Cox regression and Kaplan-Meier methods. Results were validated in an independent cohort from Perth, Australia (n = 234). ResultsBAP1 loss was found in 62% and 60.3% of all Danish and Australian samples, respectively. BAP1 loss was an independent predictor of OS in multivariate analyses corrected for histological subtype, performance status, age, sex, and treatment (hazard ratio = 2.49, p < 0.001, and 1.48, p = 0.01, respectively). First-line platinum and pemetrexed-treated patients with BAP1 loss had significantly longer median survival than those with retained BAP1 in both the Danish (20.1 versus 7.3 mo, p < 0.001) and Australian cohorts (19.6 versus 11.1 mo, p < 0.01). Survival in patients with BAP1 retained and treated with platinum and pemetrexed was similar as in those with best supportive care. There was a higher OS in patients with best supportive care with BAP1 loss, but it was significant only in the Australian cohort (16.8 versus 8.3 mo, p < 0.01). ConclusionsBAP1 is a predictive biomarker for survival after first-line combination platinum and pemetrexed chemotherapy and a potential prognostic marker in PM. BAP1 in tumor is a promising clinical tool for treatment stratification.

Quality of life of ovarian cancer patients treated with combined platinum taxane chemotherapy: a systematic review of the literature.

Chemotherapy is the cornerstone of adjuvant therapy in ovarian cancer. Its impact on the quality of life (QoL) has been addressed in several studies; however, several misperceptions concerning this affect patient counseling and physicians' ability to overcome patient fears. In the present systematic review, we sought to accumulate current evidence in the field in order to help establish robust information that will help physicians answer patients' questions. The present systematic review is based on the PRISMA guidelines. Studies that evaluated patient QoL pre-, during, and post-chemotherapy with the use of the QLQC-30 were selected for inclusion. Their methodological quality was assessed with the before-after studies tool that is proposed by the National Institute of Health (NIH). Ten studies that involved 5181 patients were included in the present systematic review. The risk of bias and methodological quality of included studies was of good and fair overall quality. Retrieved data suggest there is substantial evidence that points toward improved global QoL among ovarian cancer patients treated with taxanes-platinum combination therapy. Individual outcomes evaluated with the QLQ-C30 also provide positive results, although underreporting was noted. Despite the significant heterogeneity in outcome reporting, the findings of this study reveal the significant benefit of combined platinum taxane chemotherapy on the QoL of ovarian cancer patients and can be used for patients counseling in order to reduce refusals that arise from fear of adverse effects that may negatively affect QoL. Graphical abstract.

KEYNOTE-365 cohorts E and F: Phase 1b/2 study of pembrolizumab + lenvatinib combination therapy in patients with adenocarcinoma metastatic castration-resistant prostate cancer (mCRPC) or treatment-emergent neuroendocrine mCRPC (t-NE).

TPS215 Background: Standard of care for noncurative adenocarcinoma mCRPC is docetaxel or the next-generation hormonal agents (NHAs) abiraterone and enzalutamide. However, approximately 20% of patients develop t-NE after treatment for adenocarcinoma mCRPC; t-NE is associated with shorter survival, and it has no standard of care beyond combination platinum chemotherapy. The vascular endothelial growth factor (VEGF)/fibroblast growth factor receptor (FGFR) inhibitor lenvatinib inhibits proliferation and angiogenesis in preclinical models of adenocarcinoma prostate cancer. The phase 2 KEYNOTE-199 trial showed some antitumor activity with pembrolizumab monotherapy in docetaxel-pretreated patients with adenocarcinoma mCRPC. VEGF/FGFR inhibition combined with PD-1 inhibition may have enhanced benefit in mCRPC, for adenocarcinoma and possibly as a new treatment option for t-NE. Methods: KEYNOTE-365 (NCT02861573) is a nonrandomized, open-label, multicohort, phase 1b/2 trial designed to evaluate different pembrolizumab combination therapies in several patient populations with mCRPC. Cohort E will enroll patients with confirmed adenocarcinoma of the prostate without small cell histology, per investigator. Cohort F will enroll patients with t-NE (≥1% neuroendocrine cells in a recent biopsy specimen confirmed by central histology review). Each cohort will include patients who previously received docetaxel treatment for mCRPC. Prior treatment with ≤2 NHAs (for hormone-sensitive metastatic prostate cancer [mHSPC] or mCRPC) and 1 other chemotherapy for mCRPC is permitted. Additionally, enrollment in cohort F requires prostate cancer progression within 6 months of starting an NHA (for mHSPC or mCRPC) and within &lt; 6 cycles of docetaxel for mCRPC. Each cohort will enroll 40-100 patients with Eastern Cooperative Oncology Group performance status score of 0 or 1. Both cohorts will receive pembrolizumab 200 mg IV every 3 weeks + oral lenvatinib 20 mg once daily until disease progression, withdrawal of consent, prespecified alanine aminotransaminase or aspartate aminotransaminase level increase, or other discontinuation event. Primary end points are safety and tolerability, prostate-specific antigen (PSA) response rate, and objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR). Secondary end points include time to PSA progression; ORR and radiographic progression-free survival per Prostate Cancer Working Group 3 (PCWG3)–modified RECIST v1.1 by BICR; duration of response and disease control rate per RECIST v1.1 and PCWG3-modified RECIST v1.1 by BICR; and overall survival. These cohorts of KEYNOTE-365 are enrolling in Australia, Germany, New Zealand, Spain, and the United States. Clinical trial information: NCT02861573.

Cost-effectiveness Analysis of Lorlatinib in Patients Previously Treated with Anaplastic Lymphoma Kinase Inhibitors for Non-small Cell Lung Cancer in Greece.

Background: Non-small cell lung cancer (NSCLC), which accounts for about 80%-85% of lungcancer cases, is a leading cause of cancer-related death worldwide. Lorlatinib is a potent third-generation anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of patients with advanced, ALK-positive NSCLC previously treated with at least one second-generation ALK tyrosine kinase inhibitor.Objective: The present study assessed the cost-effectiveness of lorlatinib vs pemetrexed with platinum combination of carboplatin or cisplatin (P-ChT) in Greece.Methods: A partitioned survival model with three health states, referring to pre-progression, progressed disease, and death, was locally adapted from a Greek payer perspective over a lifetime horizon. Clinical and safety data and utility values applied in the model were extracted from the literature. A matching-adjusted indirect comparison of lorlatinib and P-ChT was performed. Only direct medical costs (€) from 2020 were included in the analysis. Primary outcomes were patient life years (LYs), quality-adjusted life years (QALYs), total costs, and incremental cost-effectiveness ratios per QALY and LY gained. All future outcomes were discounted at 3.5% per annum. A probabilistic sensitivity analysis was conducted to account for model uncertainty.Results: The analysis showed that, over a lifetime horizon, the estimated total costs of lorlatinib and P-ChT were €81 754 and €12 343, respectively. Lorlatinib was more effective than P-ChT with 2.4 and 1.5 more LYs and QALYs gained, respectively. The generated incremental cost-effectiveness ratios of lorlatinib compared with P-ChT were €28 613 per LY gained and €46 102 per QALY gained. Probabilistic sensitivity analysis confirmed the deterministic results.Conclusion: The present analysis suggests that lorlatinib may be considered as a cost-effective option compared with P-ChT in Greece for the treatment of patients with advanced, ALK-positive NSCLC whose disease has progressed after at least one second-generation ALK tyrosine kinase inhibitor. In addition, this option addresses a significant unmet medical need.

Abstract P2-12-19: Platinum is essential in neoadjuvant treatment of triple negative breast cancer: A network meta-analysis

Abstract Background: Due to the heterogeneity of triple negative breast cancer (TNBC) and variety of neoadjuvant regimen, the best way to provide optimal neoadjuvant regimen in early-stage TNBC is still a challenge. However, the preferred regimen, especially when combining target therapy such as bevacizumab, Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi), and PD-1/PD-L1 inhibitor, is still not clear. Methods: Medline, EMBASE, Cochrane Library, and Web of Science were searched in May 2020 to identify randomized controlled trials (RCTs). We conducted a fixed-effect network meta-analysis (NMA) with a Bayesian framework to assess the efficacy and safety of different neoadjuvant regimens for patients with early or locally advanced TNBC. (Registration: PROSPERO CRD42020223012). Results: A total of 35 RCTs involving 8424 participants were included, of which, 22 RCTs with 5203 patients were included in this NMA focusing on pathologic complete response (pCR). Compared to anthracycline-taxane based regimen (AT), an improvement in pCR was observed for anthracycline-taxane based combined platinum (ATP) (odds ratio [OR]=2.04, 95% credible interval [CrI]: 1.69, 2.48), TCb (T= docetaxel; Cb= carboplatin; OR=2.16, 95%CrI: 1.20, 3.91). Combining target therapy (including bevacizumab [Bev], veliparib, atezolizumab, or pembrolizumab) with AT or ATP also improved pCRs. Eleven RCTs reported serious adverse events (SAEs), and five RCTs were included in NMA. TCb was associated with less serious adverse events than AT. However, ATP, AT+Bev, ATP+Bev, ATP+Veliparib and ATP+Pembro were associated with more serious AEs than AT. Conclusions: Platinum-based neoadjuvant regimens increased pCRs in TNBC patients, among which TCb was preferred with less SAEs. Platinum-based regimens should also be considered a preferred option when combining target therapy such as Bev, PARPi, and PD-1/PD-L1 inhibitor. Citation Format: Junjie Li, Li Chen, Wei Tan, Fang Qi, Yang Zhang, Zhonghua Wang, Zhimin Shao. Platinum is essential in neoadjuvant treatment of triple negative breast cancer: A network meta-analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-19.

Systemic therapy for salivary gland malignancy: current status and future perspectives.

Salivary gland malignancies are rare neoplasms that have a broad histological spectrum and a variety of biologic behaviors. Salivary gland malignancies are known as chemo-resistant tumors, which render optimal treatment challenging. This review summarizes the role of systemic therapy for salivary gland malignancies. To date, the advantage of adding concurrent chemotherapy has remained undefined for both postoperative and inoperable locally advanced salivary gland malignancy patients undergoing radiotherapy. For recurrent/metastatic disease, local and/or systemic treatment options should be discussed in a multidisciplinary setting with consideration to both patient needs and tumor factors. For symptomatic patients or those who may compromise organ function, palliative systemic therapy can be a reasonable option based on the results of phase II studies. Platinum combination regimens as first-line therapy have been widely accepted. Personalized therapies have become established options, particularly for androgen receptor-positive, HER2-positive and NTRK fusion-positive salivary gland malignancies (i.e. androgen receptor and HER2 in salivary duct carcinoma and NTRK3 in secretory carcinoma). For patients with adenoid cystic carcinoma, multi-targeted tyrosine kinase inhibitors have also been developed. Anti-PD1 checkpoint inhibitors have shown limited activity to date. Investigation of active systemic treatments for salivary gland malignancy remains a significant unmet need. Future directions might include a more comprehensive genomic screening approach (usually next-generation sequencing-based) and combination strategies using immune checkpoint inhibitors. These are rare malignancies that require ongoing effort in the conduct of high-quality clinical trials.

Clinical and morphological aspects of neoadjuvant chemotherapy efficacy in patients with aggressive luminal HER2-negative breast cancer

Background. The role of neoadjuvant chemotherapy (NACT) in luminal HER2-negative breast cancer (BC) remains highly controversial due to the lack of reliable predictors of drug therapy efficacy.Objective: to evaluate the effectiveness of NACT in patients with aggressive luminal HER2-negative BC and to compare modern systems for assessing the pathomorphological response.Materials and methods. The tumor response to NACT regimens was assessed in 64 patients with aggressive luminal HER2-negative BC stage II–III. The median age of women was 46.5 years (range 31–76 years), 76.6 % had primary operable stages (cT1–3N0–1), locally advanced BC (cT4, cN2–3) – 23.4 % patients. The characteristics of BC were as follows: invasive ductal carcinoma (76.6 %), grade G2 and G3–54.7 % and 45.3 %, Ki-67 ranged from 20 % to 98 %, median 45 %. The ER expression level was low (1–10 %, ERlow) in 12.5 % and was more than 10 % in 87.5 % of cases. HER2 status corresponded to 0, 1+ and 2+ in the absence of gene amplification – in 50.0 %, 35.9 % and 14.1 % of patients, respectively. The rate of TILs &lt;10 %, 10–20 % and &gt;20 % was in 71.4 %, 10.7 % and 17.9 % of cases. After NACT with the inclusion of anthracyclines and taxanes ± platinum combinations (in BRCA mutated status), the patients underwent radical surgery (mastectomy or breast-conserving surgery) with an assessment of the pathological response.Results. 15.6 % of patients had a complete pathomorphological response (pCR) to treatment, which corresponded to the RCB-0 class and the pathomorphological stage ypT0N0. Residual tumor load with incomplete response was very significant – class RCB-I was noted in only 7.8 %, and RCB-II and RCB-III – in 39.1 % and 37.5 %, respectively. An increase in the size of the residual tumor and the number of affected lymph nodes were associated with an increase in the RCB class. Predictors of pCR achievement in luminal HER2-negative cancer were: grade G3, rare histological forms of BC (medullary, metaplastic), rate of TILs ≥30 %, low ER expression, and HER2 0 status.Conclusion. Assessment of Ki-67, tumor grade, ER and HER2 rate, and TILs before starting NACT will help identify a group of high sensitivity to chemotherapy and optimize the treatment strategy in aggressive luminal HER2-negative BC.

A Real-World Study on the Effectiveness and Safety of Pembrolizumab Plus Chemotherapy for Nonsquamous NSCLC

IntroductionThe real-world effectiveness of combination treatment with cytotoxic chemotherapy and programmed cell death protein-1 or programmed death-ligand 1 inhibitor for NSCLC, especially for the elderly (aged ≥75 y) or those with poor performance status (≥2), has not been fully elucidated. We investigated the real-world effectiveness and safety of this combination therapy in these populations. MethodsThis multicenter retrospective study evaluated patients who are chemo-naïve with advanced NSCLC who received a combination of platinum, pemetrexed, and pembrolizumab between December 2018 and June 2019. This was an updated prespecified secondary analysis with the primary objective of investigating the safety and effectiveness in this cohort. ResultsOverall, 299 patients were included. Multivariate analysis identified performance status (0–1) and programmed death-ligand 1 tumor proportion score (≥50%) as significant independent predictors of progression-free survival (p = 0.007, and p = 0.003, respectively). The incidence of severe adverse events (AEs) was higher in the elderly and those with poor performance status than in their younger and good performance status counterparts. A total of 71 patients developed AEs that led to treatment discontinuation, and AE-related treatment discontinuation occurred at a significantly higher rate in older patients (median [range]) (70 [46–82] y) than in younger patients (68 [31–84] y) (p <0.001). ConclusionsCombination treatment with pembrolizumab plus chemotherapy had low real-world effectiveness for poor performance status patients. Severe AEs occurred at a higher rate in the elderly and poor performance status patients, and the AE-related treatment discontinuation rate increased with age. Physicians should be cautious about using this regimen, especially in the elderly and poor performance status patients.

Cutaneous Lesions in a Patient with Cancer.

A 61-year-old male with a diagnosis of squamous cell carcinoma (SCC) of the oral cavity with pulmonary metastases was referred to us for palliative chemotherapy after the failure of a taxane and platinum combination. On examination, he had a Karnofsky performance status (PS) of 50 and a body mass index of 17.5kg/m2. Systemic examination was unremarkable except nodular and plaque-like itchy lesions on the left lateral chest wall of 3-week duration.

A Multicenter, Randomized Phase III Study Comparing Platinum Combination Chemotherapy Plus Pembrolizumab With Platinum Combination Chemotherapy Plus Nivolumab and Ipilimumab for Treatment-Naive Advanced Non–Small Cell Lung Cancer Without Driver Gene Alterations: JCOG2007 (NIPPON Study)

BackgroundFirst-line treatment of non–small cell lung cancer (NSCLC) has undergone a paradigm shift to platinum combination chemotherapy together with an immune checkpoint inhibitor, regardless of the expression level of the programmed cell death–1 (PD-1) ligand PD-L1 on tumor cells. Moreover, such chemotherapy plus nivolumab (antibody to PD-1) and ipilimumab (antibody to cytotoxic T lymphocyte–associated protein–4) prolonged survival in advanced NSCLC patients compared with chemotherapy alone. We have now designed a randomized, controlled phase III trial (NIPPON, JCOG2007) to confirm that platinum combination chemotherapy plus nivolumab and ipilimumab is superior to such chemotherapy plus pembrolizumab (antibody to PD-1) for treatment-naive patients with advanced NSCLC. Patients and MethodsChemotherapy-naïve patients aged 20 years or older with a performance status of 0 or 1 are randomly assigned in a 1:1 ratio to receive platinum combination chemotherapy and either pembrolizumab or nivolumab plus ipilimumab. Patients with known genetic driver alterations such as those affecting EGFR or ALK are excluded. Enrollment of 422 patients over 3 years at 55 oncology facilities throughout Japan is planned. The primary endpoint is overall survival. In addition, as ancillary research, metagenomic analysis of the gut microbiota will be performed with fecal samples collected before treatment onset, and the results will be examined for their association to therapeutic effect and adverse events. ConclusionIf the primary endpoint is met, platinum combination chemotherapy together with nivolumab plus ipilimumab will be established as a new, more effective standard treatment for advanced NSCLC.

Fabrication of Free-Standing Three-Dimensional Structures By Atomic Layer 3D Printing

One of the most common processes to produce microelectronics is optical lithography. It combines deposition by different thin film techniques including CVD or ALD with etching of defined structures using masks [1]. This multistep procedure is time-consuming and wasteful of material. Spatial Atomic Layer Printing offers an alternative for the direct production of defined structures and therefore for components in microelectronics.In this study, free-standing three-dimensional bridges are produced using the atomic layer 3D printer, developed by ATLANT 3D Nanosystems, that provides direct atomic layer writing process. For this purpose, two crossing lines are deposited from a support and a print material, subsequently the support material is removed via wet chemistry etching processes. To ensure an intact bridge, different material combinations of platinum, titanium dioxide, silicon dioxide and zinc oxide are used and post-processed by different etching methods. In particular, the materials used and the type of etching play an important role in producing freely standing structures. Important aspects in the preparation of the component are the influence of the etchant on the materials, the temperature used, the surface tensions of the etchant and the cleaning agent as well as the mechanical stress during the process.The most promising material combination during the test series is a printing material of titanium dioxide deposited with TTIP and H2O and a support material of zinc oxide deposited with diethylzinc and H2O. To ensure the gentlest possible etching process, the support material is removed by vapor etching using hydrochloric acid and the sample is cleaned by immersion in a mixture of 90 % ethanol and 10 % water. As a result, most of the titanium dioxide bridges are retained and can be characterized (see Figure 1). It can be demonstrated that the ATLANT 3D Nanosystems atomic layer 3D printing process can be used for the direct deposition of free-standing three-dimensional structures that can be further used to fabricate components in microelectronics (see Figure 1).Figure 1. Free-standing titanium dioxide bridges (4000 cycles) produced with zinc oxide as the support material (2000 cycles) and etched with vapor of hydrochloric acid. SEM pictures of (a) multiple bridges, (b) single free-standing bridge.[1] W. M. Moreau, Semiconductor Lithography: Principles, Practices, and Materials. 2012. Figure 1