Carboplatin Paclitaxel Research Articles

A randomized phase 3 trial of intraperitoneal versus intravenous carboplatin with dose-dense weekly paclitaxel in patients with ovarian, fallopian tube, or primary peritoneal carcinoma (a GOTIC-001/JGOG-3019/GCIG, iPocc Trial) (LBA 3)

<b>Objectives:</b> Traditionally, the target of intraperitoneal (IP) chemotherapy for ovarian cancer was patients with minimal residual disease after debulking surgery. However, our pharmacological study suggested that IP carboplatin therapy should also be feasible for patients with larger size residual disease, and our previous phase 2 study demonstrated a satisfactory response rate of IP carboplatin plus dose-dense paclitaxel (ddTCip) regimen in patients with macroscopic residual disease after initial surgery for ovarian (OV), fallopian tube (FT), and primary peritoneal (PP) carcinoma. The purpose of this study is to assess whether IP administration of carboplatin is superior to intravenous (IV) administration of carboplatin (ddTCiv regimen) in OV, FT, and PP carcinoma patients with either minimal or macroscopic residual disease. <b>Methods:</b> Eligible patients were those with newly diagnosed stages II-IV disease. All patients were to undergo an initial laparotomy or laparoscopy with primary debulking surgery if possible. Before abdomen was closed, patients were randomized to either IV or IP arm. An IP port and catheter was placed if the patient was assigned to IP arm. Chemotherapy regimen was either IV paclitaxel plus IV carboplatin (IV arm) or IV paclitaxel plus IP carboplatin (IP arm). Dose of paclitaxel was 80 mg/m² Q1W and dose of carboplatin was at an area under the curve (AUC) of 6 Q3W. Each patient was to receive 6 to 8 cycles of chemotherapy. Patients with bulky residual disease were allowed to undergo interval debulking surgery followed by assigned arm regimen up to 8 cycles total. Primary endpoint was PFS, and secondary endpoints included OS, safety, QOL, and cost/benefit. <b>Results:</b> Total of 655 patients were randomized between 2010 and 2016 from Japan, Singapore, Korea, New Zealand, USA, and Hong Kong. Stage distribution was II (n= 88), III (n=448), and IV (n=119). Size of residual disease at randomization was either 0 cm (n=163), < 1 cm (n=97), 1-2 cm (n=33), or >2 cm (n=362). Histological types were serous (n=420), endometrioid (n=61), clear cell (n=74), and others (n=100). Median follow-up was 55.7 months. IP chemotherapy significantly improved PFS in the ITT population (HR=0.83, 95%CI:0.69-0.99, p=.041) and in the 602 eligible patients (HR=0.78, 95%CI:0.65-0.94, p=.009). Median PFS for ITT population was 20.7 (95%CI: 18.1-22.8) months in the IV arm and 23.5 (95%CI: 20.5-26.9) months in the IP arm. Median PFS for eligible patients was 20.0 (95%CI: 18.0-22.2) months in the IV arm and 22.9 (95%CI:19.6-26.9) months in the IP arm. Subset analysis showed that the survival benefit was greater in patients with larger size residual disease. Toxicity profile was essentially equivalent in both arms except for catheter-related toxicities (11.8%). <b>Conclusions:</b> ddTCip chemotherapy improved the PFS over ddTCiv regimen in patients with OV, FT, and PP carcinoma regardless of the residual tumor size after initial surgery.

Bevacizumab for advanced ovarian cancer treatment. A GRADE based approach

&#x0D; Background: in advanced ovarian cancer, over the last 10 years no studies have demonstrated more appropriate therapeutic options compared to the current standard Carboplatin-Paclitaxel (Cb-P) regimen. Two phase III randomized studies (GOG-218 36 and ICON-7 37) have recently demonstrated the efficacy of bevacizumab (recombinant monoclonal antibody that binds with a high affinity to VEGF-A) in adjunct to Cb-P, with 12-15 months maintenance treatment.&#x0D; Methods: the quality of evidence provided was assessed by the use of the GRADE method. Each outcome (deemed to be essential for the purpose of evaluation of the intervention) was assessed to express the degree of confidence in the entity of the beneficial and/or harmful effects of the intervention. Thus, limitations in the quality of conducting the studies (risk of bias), direct applicability/relevance of results to the target population, and precision of results were taken into account.&#x0D; Results: the GOG-218 and the ICON7 study (high-risk subgroup) demonstrated with MODERATE confidence an improvement in critical outcomes PFS and OS, with an absolute reduction of 96 (GOG-218) – 103 (ICON-7) episodes of progression, and 40 (GOG-218) – 135 (ICON-7) deaths per 1 000 patients. A marked increase in risk of hypertension of Grade ≥3 was observed, with an absolute increase of 59 episodes per 1 000 patients in the ICON-7 study, and 157 episodes in the GOG-218 study, respectively, the majority of which were controlled by means of appropriate treatment. The increased risk of other adverse events considered was negligible.&#x0D; Conclusions: the positive effects produced should be viewed as taking prevalence over the negative effects (FAVOURABLE benefit/harm ratio).&#x0D;

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.

Abstract 1973: Patients with operable esophageal cancer and improved responses to combined chemoradiotherapy and immunotherapy display distinct microbiome profiles enriched in multiple Bacteroides species

Abstract Background: Preclinical and clinical data indicate that neoadjuvant chemoradiotherapy (CRT) may prime an anti-tumor immunological response in esophageal cancer driven by intratumoral CD8+ T cells and PD-L1 expression. LAG-3 is also highly expressed in esophagogastric cancers. The microbiome, a novel and potentially modifiable, biomarker of IO response, has not yet been examined in the neoadjuvant setting in esophageal cancer and is the goal of our study. Methods: Fecal samples were collected from patients with stage II/III esophageal or gastroesophageal junction carcinoma eligible for curative resection treated with the standard of care regimen of carboplatin paclitaxel (50mg/m2), radiation 50.4 Gy in 28 fractions and an Ivor-Lewis esophagectomy 6-10 weeks after last CRT and immunotherapy (IO) dose. Patients on arm A (n=11) received 2 cycles of induction with nivolumab plus 3 additional cycles on week 1, 3 and 5 of CRT. Patients on arm B (n=8) received nivolumab plus relatlimab on the same schedule (Clinical trial: NCT03044613). We examined longitudinal fecal samples from n=19 patients across both arms (n=90 samples) using 16S rRNA amplicon sequencing. Patients were classified based on pathological response: complete response (CR) and grades 1, 2, and 3 (G1, G2, G3) with increasing residual tumor visible in the resected specimen. Sequencing data was trimmed and filtered for contaminants, followed by high-resolution taxonomic assignment and normalization of reads across all samples. Analysis was performed using multiple metrics for alpha diversity and beta-diversity, with principal coordinates analysis/PERMANOVA, and pathway analysis using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Results: Patients with improved response in the neoadjuvant setting (CR/G1 vs G2/G3) grouped in distinct clusters using Bray-Curtis (p &amp;lt; 0.001). Patients with CR had higher alpha diversity, using both measures of richness and evenness, compared to patients with a G3 responses (p &amp;lt; 0.03). Specifically, family Bacteroidaceae and genus Bacteroides were enriched in patients with CR vs G3 (p &amp;lt; 0.02). At the species level, B. finegoldii, B. ovatus, and B. uniformis were enriched in patients with CR vs G3 (p &amp;lt; 0.02). In contrast, genus Klebsiella and Clostridium termitidis were enriched in patients with a poor response, G3 (p &amp;lt;0.001, both). Pathway analysis found two metabolic pathways enriched in patients with CR: secondary bile acid biosynthesis (p=0.005) and lysine biosynthesis (p=0.02). Conclusions: Patients with operable esophageal cancer and improved responses to combined CRT and IO had distinct microbiome profiles enriched in multiple Bacteroides species. Further analyses and validation efforts are underway to confirm metabolomic pathways. Citation Format: Fyza Y. Shaikh, James R. White, Ronan J. Kelly, Ali H. Zaidi, Jenna V. Canzoniero, Josephine L. Feliciano, Russell K. Hales, K Ranh Voong, Richard J. Battafarano, Blair A. Jobe, Stephen C. Yang, Stephen Broderick, Jinny Ha, Kellie N. Smith, Elizabeth Thompson, Eun J. Shin, Ali I. Amjad, Patrizia Guerrieri, Benny Weksler, Chen Hu, Valsamo Anagnostou, Vincent K. Lam, Cynthia L. Sears. Patients with operable esophageal cancer and improved responses to combined chemoradiotherapy and immunotherapy display distinct microbiome profiles enriched in multiple Bacteroides species [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 1973.

Randomized phase III study of nivolumab and ipilimumab versus carboplatin-based doublet in first-line treatment of PS 2 or elderly (≥ 70 years) patients with advanced non–small cell lung cancer (Energy-GFPC 06-2015 study).

9011 Background: Combination of anti-PD1 and CTLA4 have showed superiority to chemotherapy (CT) in advanced non–small cell lung cancer (NSCLC), but data for fit elderly or PS2 patients are scarce. Methods: eNErgy compared the combination of nivolumab ipilimumab (N-I) to a platinum doublet in elderly or PS2 patients with advanced NSCLC. Primary endpoint was overall survival (OS), secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Main inclusion criteria were: stage IV histologically proven NSCLC, age ≥ 70 y, and PS 0/1/2 or age &lt; 70 and PS2, EGFR ALK/ROS1 negative, judged fit enough to receive a platinum doublet. The main exclusion criteria were active cerebral metastasis or contraindication to N-I. Patients were randomly selected 1/1, stratified by age (≥ 70 vs. &lt; 70 y), PS (0/1 vs. 2), and histology (squamous vs. no-squamous). Nivolumab (240 mg, 2w), ipilimumab, 1 mg/kg, 6w, was administrated until progression or unacceptable toxicity. CT was planned for 4 cycles, with carboplatin (AUC5) and pemetrexed (500 mg/m2, 3w) or paclitaxel (90 mg/m2, d1,d8, d15); 242 patients had to be randomized to detect a treatment effect hazard ratio (HR) on OS of 0.65, with a 85% power at a 2-sided alpha level of 5%. Results: A preplanned interim analysis carried out after observation of 33% of deaths, out of 174 randomized patients, showed a risk of futility especially for PS 2 patients, HR: 1.8 (95% CI, 0.99-3.3). This led to a halt in randomization but continued follow-up of the 204 patients randomized at the time of the decision. The current final analysis is carried out 18 months after the inclusion of the last patient: men, 71%, median age 74 (51-89, PS 0/1/2 in 30%, 37.5%, and 36.6% respectively), smokers or former smokers in 25.5 and 64.4%, with 62% adenocarcinoma. The median OS of N-I and chemo arms were 14.7 (95% CI, 8.0-19.7) and 9.9 (95% CI, 7.7-12.3) months, HR 0.85, 95% CI, 0.62-1.16. The subgroup analyses showed a significant benefit of the association N-I compared to CT for elderly PS 0/1 patients, with median OS of 22.6 (95% CI, 18.1-36) vs. 11.8 (95% CI, 8.9-20.5) months, p = 0.02. In PS2 patients, median OS of N-I and CT arms was 2.9 (1.4-4.8) vs. 6.1 (3.5-10.4) months (p = 0.22). Median PFS was significantly in favor of N-I arm in the entire population: 5.5 (2.8-8.7) vs. 4.6 (3.5-5.6); p = 0.015. Safety was similar with 31.4% of patients with grade ≥ 3 related SAES in N-I arm vs. 49.5% for CT. Treatment was discontinued for toxicity in 28.6% in N-I arm vs. 22.3% of patients in CT arm. Conclusions: Despite no statistically significant benefit in OS observed in the entire population, there was a clinical signal of efficacy of N-I combination over platinum doublet in elderly NSCLC patients PS 0-1 with a significant benefit of OS of 22.6 months vs. 11.8 for CT arm. Clinical trial information: NCT03351361.

Clinical efficacy and safety of the BAT1706 (proposed bevacizumab biosimilar) compared with reference bevacizumab in patients with advanced nonsquamous NSCLC: A randomized, double-blind, phase III study.

9041 Background: A Randomized, Double-blind, Phase III Study was conducted to confirm clinical similarity between BAT1706, a proposed biosimilar to reference bevacizumab, and EU-bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC). Methods: Patients were randomized 1:1 to BAT1706 plus paclitaxel and carboplatin (Arm A) or EU-bevacizumab plus paclitaxel and carboplatin (Arm B) given three weeks for 6 cycles, followed by maintenance therapy with BAT1706 or EU- bevacizumab. The primary endpoint was overall response rate at Week 18 (ORR18). Secondary endpoints included ORR at Week 6 and 12, best ORR, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Results: A total of 651 patients were randomized: BAT1706 (n = 325) or EU- bevacizumab (n = 326). In total, 649 randomized patients (BAT1706 (n = 325) or EU- bevacizumab (n = 324)) received at least one cycle of combination treatment. The median duration of therapy was 29.1 weeks (ranging from 3.0 to 62.1 weeks) in the Arm A and 27.0 weeks (ranging from 3.0 to 53.9 weeks) in the Arm B. The extent of exposure to BAT1706 and EU- bevacizumab was similar between these two arms. Overall, the proportion of patients achieving an ORR by Week 18 was comparable across Arm A and B (48.0% and 44.5%). The ORR risk ratio of 1.08 with 90% CI (0.94, 1.24) and the ORR risk difference of 0.03, with 95% CI (-0.04, 0.11) were within pre-specified equivalence margin. In addition, the multivariate-adjusted risk ratio was 1.07, with a 90% CI (0.93, 1.22). The ORR18 risk difference between BAT1706 and EU- bevacizumab was 0.03, with the 2-sided 95% CI (-0.04, 0.11) that fell entirely within pre-specified equivalence margin. In addition, the multivariate-adjusted risk difference was 0.03, with a 95% CI (-0.04, 0.11). The hazard ratio stratified for time to PFS was 0.915 and the PFS rate at 12 months was 20.7% versus 21.8%. At the end of the study, there were no significant differences between both the treatments. The incidence of treatment-emergent adverse events (TEAEs) and study drug-related TEAEs was similar between these two arms. Overall, the safety profiles of BAT1706 were consistent with that of EU- bevacizumab, no new safety signals or noticeable trends were observed. The mean serum concentrations were comparable between BAT1706 and EU- bevacizumab over the entire sampling interval both in pre-dose and post-dose. The incidence of positive anti-drug antibodies results was low (≤5%) and decreased over time in both treatment arms. No patient was detected to have positive neutralizing anti-drug antibody result during the study. Conclusions: BAT1706 demonstrated clinical equivalence to reference EU-bevacizumab in terms of efficacy, safety, pharmacokinetics, and immunogenicity. Clinical trial information: NCT03329911.

Pharmacologic modulation of 5-fluorouracil by folinic acid and pyridoxine for treatment of patients with advanced breast carcinoma

High concentration pyridoxal 5’-phosphate, the cofactor of vitamin B6, potentiates cytotoxicity in cancer cells exposed to 5-fluorouracil (FUra) and folinic acid (FA). We studied the effect of high-dose pyridoxine on antitumor activity of regimens comprising FUra and FA in 27 advanced breast carcinoma patients. Of 18 previously untreated patients, 12 had tumors that did not overexpress HER2 (Group I), and 6 that overexpressed HER2 (Group II). Nine patients (Group III) had prior chemotherapy. Group I received AVCF (doxorubicin, vinorelbine, cyclophosphamide, FUra, FA) or FAC (doxorubicin, cyclophosphamide, FUra, FA) followed by TCbF (paclitaxel carboplatin, FUra, FA). Groups II, and III received TCbF. Pyridoxine iv (1000–3000 mg/day) preceded each FA and FUra. Group II also received trastuzumab and pertuzumab. 26 patients responded. Three patients in Group I had CRs and 9 had PRs with 62–98% reduction rates; 4 patients in Group II had CRs and 2 had PRs with 98% reduction. Of 7 measurable patients in Group III, 2 attained CRs, and 5 had PRs with 81–94% reduction rates. Median time to response was 3.4 months. Unexpected toxicity did not occur. This pilot study suggests that high-dose vitamin B6 enhances antitumor potency of regimens comprising FUra and FA.

P122 EXTENDED PULMONARY ADENOCARCINOMA INFILTRATING THE LEFT ATRIUM

Abstract Cardiac tumors can be primary (benign or malignant) or metastatic (malignant) and can arise in any part of the heart tissue, causing obstruction in the inflow or outflow tract of the valves, thromboembolism, arrhythmias and pericardial disorders. Diagnosis is made by echocardiography and, frequently, by cardiac MRI. The treatment of metastatic malignancies depends on the type and origin of the tumor; however, the prognosis is generally poor.73–year–old patient, he reaches echocardiographic control after having started, 5 months earlier, chemotherapy with weekly carboplatin–paclitaxel scheme for the diagnosis of primary left hilar pulmonary heteroplasia. In medical history: systemic arterial hypertension, iron deficiency anemia and thrombocytopenia in a patient with a history of alcohol–related liver cirrhosis and esophageal varices.On transthoracic echocardiogram (Figures 1 and 2): normal size and bi–ventricular systolic function; mild aortic and mitral insufficiency. Presence of non–mobile isoechoic oval mass adhering to the left atrium, 43 x 27 mm in size, at the outlet of the left pulmonary veins, which does not cause obstruction to the atrio–ventricular blood supply.On CT of chest without and with contrast (Figure 3): primary heteroplastic left hilar pulmonary lesion that infiltrates the left atrium and obliterates the left main bronchus before the bifurcation and the bronchus for the left upper lobe; the corresponding pulmonary vessels also appear infiltrated. The diagnosis was therefore of intracardiac tumor secondary to primary lung lesion.Secondary cardiac tumors are about 20 times more frequent than primary ones. The ability of the tumor to spread to the heart depends on the relationship between the specific biological potential of the primary tumor, the location of the latter and the contractile and draining force of the myocardium.Cardiac metastases can involve, also in combination, pericardium, epicardium, myocardium, endocardium, heart chambers or create endocavitary neoplastic thrombus. Tumors spread to the heart through four possible routes: direct extension, the blood route, the lymphatic route, intracavitary diffusion from the inferior vena cava or pulmonary veins, as in our case.The haemodynamic alterations they cause depend on the engagement of the atrioventricular orifice by the tumor mass.

Paclitaxel-carboplatin and bevacizumab combination with maintenance bevacizumab therapy for metastatic, recurrent, and persistent uterine cervical cancer: An open-label multicenter phase II trial (JGOG1079)

ObjectiveThis multicenter, open-label, phase II study aimed to evaluate the efficacy and safety of paclitaxel–carboplatin, bevacizumab, and bevacizumab-based maintenance therapy for metastatic, recurrent, and persistent uterine cervical cancer. MethodsPatients with measurable diseases that were not adapted to regional therapies, such as surgery or radiotherapy, and were systematic chemotherapy-naïve were eligible. The participants received paclitaxel (175 mg/m2), carboplatin (AUC 5), and bevacizumab (15 mg/m2) every three weeks until disease progression or unacceptable adverse events occurred. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall response rate (ORR), overall survival (OS), safety, and time to treatment failure. ResultsSixty-nine patients were analyzed using our protocol. The median paclitaxel– carboplatin therapy duration was six cycles; 40% of patients received bevacizumab maintenance therapy. The median PFS was 11.3 months. The median OS was not reached; the median time to treatment failure was 5.9 months. The ORR was 79.7% [95% confidence interval (CI) 63.8–88.4]; 16 patients (23.2%) showed complete response (CR) and 39 patients (56.5%) showed partial response (PR). The median PFS was 14.3 months (95% CI 7.3–17 months) for the 25 patients who received maintenance therapy and 7.4 months (95% CI 6.1–11 months) for nonrecipients (p = 0.0449). Gastrointestinal perforation/fistulas occurred in four patients (5.6%), all of whom had a history of radiation therapy. ConclusionsPaclitaxel–carboplatin and bevacizumab therapy is an acceptable and tolerable treatment for advanced or recurrent cervical cancer.

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...

Crosstalk between the gut microbiome and clinical response in locally advanced thoracic esophageal squamous cell carcinoma during neoadjuvant camrelizumab and chemotherapy.

BackgroundThe gut microbiome is associated with the response to immunotherapy in a variety of advanced cancers. However, the influence of the gut microbiome on locally advanced esophageal squamous cell carcinoma (ESCC) during programmed cell death protein 1 (PD-1) antibody immunotherapy plus chemotherapy is not clearly demonstrated. To explore the crosstalk between the gut microbiome and clinical response in locally advanced thoracic ESCC during neoadjuvant camrelizumab and chemotherapyMethodsPatients who were diagnosed with locally advanced thoracic ESCC and had not received treatment were enrolled. The treatment regimen was two cycles of camrelizumab combined with carboplatin and albumin paclitaxel before surgery. The research endpoints were pathological complete response (pCR) and major pathological response (MPR). Fecal samples were collected at three time points: before neoadjuvant therapy, after two cycles of neoadjuvant therapy, and after surgery. We performed 16S ribosomal ribonucleic acid (rRNA) V3–V4 sequencing of the gene amplicons of fecal samples, as well as bacterial diversity and differential abundance analyses.ResultsA total of 46 patients were recruited, and 44, 42, and 35 fecal samples were collected at the three time points, respectively. Statistically significant differences were observed in the amplicon sequence variant (ASV)-level alpha diversity indices, including Chao1, Shannon, and Good’s coverage, between the three time points. The non-pCR-enriched gut microbiota included Proteobacteria, Dialister, Aeromonadales, Pseudomonadales, Thermi, Deinococci, Moraxellaceae, Rhodocyclales, Rhodocyclaceae, and Acinetobacter. The non-MPR-enriched gut microbiota included Pseudomonadales and the mitochondria family. The MPR-enriched gut microbiota included the Barnesiellaceae, Pyramidobacter, Dethiosulfovibrionaceae, Odoribacteraceae, Butyricimonas, Prevotella, Barnesiella, and Odoribacter. Patients with ≥3 grade adverse events (AEs) exhibited enrichment in the Succiniclasticum, Nakamurella, Rhizobium, Granulicella, Phyllobacteriaceae, Pelagibacteraceae, Actinosynnemataceae, Aquirestis, Flavisolibacter, Chelativorans, Coxiellaceae Acidicapsa, Acidobacteriaceae, Lentzea, Staphylococcus, Plesiomonas, Dysgonomonas, Pseudonocardia, and Ellin6075.ConclusionsWe found that the diversity of the gut microbiome declined after neoadjuvant PD-1 antibody immunotherapy plus chemotherapy and surgery. Patients with pCR had different types and proportions of gut microbiota before treatment compared to those without pCR. We also observed the difference between patients with or without ≥ grade 3 AEs. The taxonomic features of the gut microbiome are potential biomarkers that could predict the pathological response and AEs.

Carboplatin plus nanoparticle albumin-bound paclitaxel for the treatment of thymic carcinoma.

Thymic carcinoma is a relatively rare type of malignant tumor. The present retrospective study evaluated the efficacy and safety of carboplatin plus nanoparticle albumin-bound paclitaxel for the treatment of advanced thymic carcinoma. The study included data from 12 patients with advanced thymic carcinoma treated in the Nippon Medical School Hospital (Tokyo, Japan). Response to treatment, patient survival and treatment safety were assessed. The objective response rate was 66.7% (8/12 patients). Disease control was achieved in 11 patients (91.7%). At the median follow-up time of 27.6 months (range, 6.2-75.1 months), the median progression-free survival and median first-line overall survival times were 16.7 months [95% confidence interval (CI), 13.2-37.7] and 14.3 months (95% CI, 4.7-54.6), respectively. There was no occurrence of febrile neutropenia or treatment-related death. The results of the present study showed that carboplatin plus nanoparticle albumin-bound paclitaxel was effective and safe. Therefore, it is a promising chemotherapy regimen for the treatment of advanced thymic carcinoma.

Weekly versus tri-weekly paclitaxel with carboplatin for first-line treatment in women with epithelial ovarian cancer.

Epithelial ovarian cancer is the sixth most common cancer worldwide: 295,414 new cases were diagnosed in 2018, with 184,799 deaths. The lack of an effective screening strategy has led to the majority of women being diagnosed at an advanced stage. For these women, intravenous carboplatin combined with paclitaxel for six cycles is widely accepted as the standard first-line treatment for epithelial ovarian cancer, in combination with debulking surgery. However, there is conflicting evidence regarding the optimal dosing schedule of paclitaxel when combined with carboplatin in this setting. To compare the efficacy and tolerability of intravenous weekly paclitaxel with that of tri-weekly paclitaxel, in combination with intravenous carboplatin, as first-line treatment for epithelial ovarian cancer (defined as epithelial ovarian, primary peritoneal and fallopian tube cancer). We searched CENTRAL, MEDLINE, and Embase databases for relevant studies up to 15 November 2021, using keywords and MeSH terms. We additionally handsearched conference libraries, online clinical trial databases and screened through lists of retrieved references. We Included randomised controlled trials (RCTs) comparing weekly paclitaxel in combination with carboplatin versus tri-weekly paclitaxel in combination with carboplatin, for treatment of newly-diagnosed epithelial ovarian cancer. We used the hazard ratio (HR) to estimate the primary efficacy outcomes progression-free (PFS) and overall survival (OS). We used the risk ratio (RR) to estimate the primary toxicity outcome of severe neutropenia and secondary outcomes of quality of life (QoL) and treatment-related adverse events. Two review authors independently selected studies, extracted data, and assessed risk of bias, using standard Cochrane methodological procedures. We included individual participant data (IPD) from one of the included studies, ICON-8, provided by the study team. We analysed data using a random-effects model in Review Manager 5.4 software. Additionally, we reconstructed IPD for PFS and OS data from published Kaplan-Meier curves from all studies and subsequently pooled these to analyse the two primary efficacy outcomes. From 2469 records, we identified four eligible RCTs with data for 3699 participants. All eligible studies were included in the main meta-analysis and reported on PFS and OS. There was likely a slight improvement in PFS when paclitaxel was dosed weekly compared to tri-weekly (HR 0.89, 95% confidence interval (CI) 0.81 to 0.98; 4 studies, 3699 participants; moderate-certainty evidence). We found little to no improvement in OS when paclitaxel was dosed weekly compared to tri-weekly (HR 0.92, 95% CI 0.79 to 1.06; 4 studies, 3699 participants; high-certainty evidence). There was likely little to no difference in high-grade (grade 3 or 4) neutropenia when paclitaxel was dosed weekly compared to tri-weekly (RR 1.11, 95% CI 0.86 to 1.43; 4 studies, 3639 participants; moderate-certainty evidence). However, weekly paclitaxel increased high-grade (grade 3 or 4) anaemia when compared to tri-weekly dosing (RR 1.57, 95% CI 1.12 to 2.20; 4 studies, 3639 participants; high-certainty evidence). There may be little to no difference in high-grade neuropathy when paclitaxel was dosed weekly compared to tri-weekly (RR 1.12, 95% CI 0.64 to 1.94; 4 studies, 3639 participants; low-certainty evidence). The overall risk of detection bias and performance bias was low for OS, but was unclear for other outcomes, as treatments were not blinded. The risk of bias in other domains was low or unclear. We note that OS data were immature for three of the included studies (GOG-0262, ICON-8 and MITO-7). Weekly paclitaxel combined with carboplatin for first-line treatment of epithelial ovarian cancer likely improves PFS slightly (moderate-certainty evidence) but not OS (high-certainty evidence), compared to tri-weekly paclitaxel combined with carboplatin. However, this was associated with increased risk for high-grade anaemia, treatment discontinuation, dose delays and dose omissions (high- to low-certainty evidence). Our findings may not apply to women receiving bevacizumab in first-line therapy, those receiving treatment in the neo-adjuvant setting, or those with rare subtypes of clear cell or mucinous ovarian cancer.

Clinical efficacy of atezolizumab plus bevacizumab and chemotherapy in KRAS-mutated non-small cell lung cancer with STK11, KEAP1, or TP53 comutations: subgroup results from the phase III IMpower150 trial

BackgroundThe efficacy of atezolizumab (A) and/or bevacizumab (B) with carboplatin/paclitaxel (CP) chemotherapy was explored in the phase III, randomized IMpower150 study in patients with non-squamous non-small cell lung cancer (NSCLC)...

The efficacy and safety of neoadjuvant camrelizumab and chemotherapy for locally advanced thoracic esophageal squamous cell carcinoma.

278 Background: To explore the efficacy and safety of neoadjuvant camrelizumab and chemotherapy for locally advanced thoracic esophageal squamous cell carcinoma (ESCC) by an open label, single-arm, phase 2 clinical trial (ClinicalTrials.gov, Identifier number: NCT04506138). Methods: The eligible patients were arranged to receive 2 cycles of camrelizumab (200mg, day 1) combined with carboplatin (AUC = 5, day 1) and albumin paclitaxel (100 mg/m2, day 1, 8). All treatments were given intravenously in 3-week cycle. Patients underwent surgery within 4-6 weeks after the completion of neoadjuvant treatment. The primary endpoint was pathologic complete response (pCR), and secondary endpoints were major pathological response (MPR), safety and feasibility. The quality of life (QoL) was assessed by the Functional Assessment of Cancer Therapy-Esophageal (FACT-E) scale and EQ-5D-3L scale. Results: A total of 46 patients were recruited, among whom the clinical stage II, III, and IVa at baseline were 11 (23.9%), 33 (71.7%), and 2 (4.3%), respectively. Forty-five patients completed 2 cycles of neoadjuvant treatment. One patient received 1 cycle of neoadjuvant treatment and then lost to be followed up. Eight patients did not receive surgery. Except 1 patient accept exploratory surgery, 37 patients (37/46, 80.4%) achieved R0 resection. Eight patients (8/37, 21.6%) had pCR in both primary tumors and lymph nodes. MPR of primary tumors and lymph nodes was observed in 18 patients (18/37, 48.6%). During neoadjuvant treatment period, all 46 patients presented with treatment-related AEs (TRAEs) of any grade. Seven patients (7/46,15.2%) experienced grade ≥ 3 TRAEs. One patient suffered grade 5 immune-associated pneumonia. The most common TRAEs were anemia (32/46, 70.0%), followed by thrombocytopenia (15, 32.6%), leukopenia (14, 30.4%), neutropenia (13, 28.3%), rash (12, 26.1%), reactive cutaneous capillary endothelial proliferation (RCCEP) (7, 15.2%). The median interval between the first cycle of neoadjuvant treatment and surgery was 64 days (range, 56-77 days). Symptom scores in FACT-E scale were improved by neoadjuvant treatment (t = -2.60, P = 0.01). PD-L1 CPS (&lt; 10 vs ≥ 10), PD-L1 TPS (&lt; 1% vs ≥ 1%) and TMB (split according to top 20% of TMB value) had no effect on the pCR rate and MPR rate. Conclusions: Neoadjuvant camrelizumab combined with chemotherapy achieved a promising pathologic response, which was effective and safe. Meanwhile, neoadjuvant treatment improved QoL of patients. Some larger multi-center trials are undergoing for further confirmation of efficacy and safety. Clinical trial information: NCT04506138.

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.

Neoadjuvant and Adjuvant Systemic Therapy for Newly Diagnosed Stage II-IV Epithelial Ovary, Fallopian Tube, or Primary Peritoneal Carcinoma: A Practice Guideline.

Background: This study aims to provide guidance for the use of neoadjuvant and adjuvant systemic therapy in women with newly diagnosed stage II–IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma. Methods: EMBASE, MEDLINE, and Cochrane Library were investigated for relevant systematic reviews and phase III trials. Articles focusing on consolidation and maintenance therapies were excluded. Results: For women with potentially resectable disease, primary cytoreductive surgery, followed by six to eight cycles of intravenous three-weekly paclitaxel and carboplatin is recommended. For those with a high-risk profile for primary cytoreductive surgery, neoadjuvant chemotherapy can be an option. Adjuvant chemotherapy with six cycles of dose-dense weekly paclitaxel plus three-weekly carboplatin can be considered for women of Japanese descent. In women with stage III or IV disease, the incorporation of bevacizumab concurrent with paclitaxel and carboplatin is not recommended for use as adjuvant therapy unless bevacizumab is continued as maintenance therapy. Intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel can be considered for stage III optimally debulked women who did not receive neoadjuvant chemotherapy. However, intraperitoneal administration of chemotherapy with bevacizumab should not be considered as an option for stage II–IV optimally debulked women. Discussion: The recommendations represent a current standard of care that is feasible to implement and valued by both clinicians and patients.

Bevacizumab in combination with paclitaxel and platinum for previously treated advanced thymic epithelial tumors

There are no optimal regimens for advanced thymic epithelial tumors (TETs) when frontline chemotherapy fails. In this study, we aimed to assess the activity of Bevacizumab in combination with a routine chemotherapeutic regimen. Patients with advanced TETs who had failed after previous chemotherapy were enrolled in this study. Paclitaxel (160mg/m2) andcisplatin (70mg/m2) orcarboplatin (area under the curve, 6) plus Bevacizumab (7.5mg/kg) were intravenously injected on day 1.The treatment was repeated every 3weeks until the disease progressed or intolerable toxicities occurred. Between March 2018 and August 2020, a total of 49 patients (21 thymoma and 28 thymic carcinoma) received the new treatment. There were 28 men and 21 women with a median age of 50years (range: 21-73years). The median number of cycles was 3 (range: 1-6) per patient. The objective response rate (ORR) for all patients was 43% (21/49). The ORRs for thymoma and thymic carcinoma were 24% and 57%, respectively. The median progression-free survival for thymoma and thymic carcinoma was 6 and 8months, respectively. Hematological toxicities were the main side effects. Paclitaxel and platinum plus Bevacizumab showed promising effects in refractory or relapsed advanced TETs without severe toxicity. Even when applied as salvage therapy, this regimen resulted in a better ORR than frontline chemotherapy.

Cisplatin Versus Carboplatin and Paclitaxel in Radiochemotherapy for Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma.

The implementation of a platinum-containing regimen is recommended for definitive and adjuvant therapy of patients with locally advanced head and neck tumour. We compared the conditions for the use of cisplatin or carboplatin/paclitaxel or for changing between these two regimens on a clinic-specific basis. We evaluated 150 patients with advanced head and neck squamous cell carcinoma who received simultaneous radiochemotherapy at our institution between 2012 and 2017. Chemotherapy with weekly doses of cisplatin (40 mg/m2, group 1) or, in cases of impaired renal and/or cardiac function, with weekly doses of carboplatin AUC2 and paclitaxel (45 mg/m2, group 2), was performed as a first-choice therapy. If toxicities occurred in group 1, treatment was switched to the carboplatin/paclitaxel regimen (group 3). Patient- and therapy-related parameters, toxicity and survival data were compared across groups. We examined 99, 30, and 21 patients in each group who received at least 1 course of chemotherapy. Group 3 patients switched from cisplatin to carboplatin/paclitaxel after a median of 3 courses due to nephrotoxicity (95.2%). The target of at least 5 chemotherapy courses was most frequently achieved by patients in group 1 (69.7%), followed by group 3 (61.9%) and then group 2 (40.0%). Multivariate analysis revealed that patients who switched groups were more likely to be over 60 years old (p=0.021), undergo definitive radiochemotherapy (p=0.049) and develop higher nephrotoxicity (p=0.036) than group 1 patients. Outcomes did not differ between groups. When cisplatin application is contraindicated due to renal- or cardiotoxicity, carboplatin/paclitaxel is an appropriate option.