Browsing Over 783 Presentations
344P - Single-centre analysis of anti-resorptive agent-related osteonecrosis of the jaw in lung cancer patients (ID 135)
- Kohei Fujita (Kyoto, Japan)
Abstract
Background
Over the past two decades, anti-resorptive agent-related osteonecrosis of the jaw (ARONJ) has become a growing concern. We examined the incidence of ARONJ and identified its risk factors in lung cancer patients in the real-world clinical setting. To our knowledge, we are the first to do so.
Methods
We retrospectively analysed lung cancer patients with bone metastases who had received anti-resorptive agents (zoledronate or denosumab) at the National Hospital Organization Kyoto Medical Center from October 2012 to September 2018. All ARONJ cases were diagnosed by the dentists according to the established diagnostic criteria.
Results
A total of 171 patients were reviewed, 13 (7.6%) of whom experienced ARONJ. Among the 13 patients, six (46.2%), four (30.8%), and three (23.1%) had adenocarcinoma, squamous carcinoma, and not otherwise specified, respectively. ARONJ was stage 2 in three (23.1%) patients and stage 3 in 10 (76.9%). More cycles of anti-resorptive agents (OR, 11.54; 95% CI, 2.47–53.99; P <0.01), and longer survival duration (≥2 years) (OR, 12.16; 95% CI, 3.17–46.65; P <0.01) were independently associated with ARONJ in a multivariate analysis.
Conclusions
The incidence of ARONJ was relatively high in lung cancer patients with bone metastases. When using anti-resorptive agents, oncologists should closely monitor patients for ARONJ during the course of treatment and regularly consult with dentists.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
312P - Identification of neoantigen-specific T cell response and anti-tumour immunity in pancreatic cancer (ID 171)
- Xiaoxiao Du (Hangzhou, China)
Abstract
Background
Pancreatic cancer is a highly aggressive malignancy with relatively low morbidity, which is marked by insidious clinical symptoms but rapid development. The therapeutic options of PC are limited for the insensitivity of traditional chemoradiotherapies. The neoantigen-based vaccine is an emerging tumor immune therapeutic option, but limited evidence proved the efficient therapeutic response in pancreatic cancer.
Methods
Whole exome sequencing and bioinformatic analysis as well as quantitative real-time PCR of our previously established human pancreatic cancer cell line were performed to identify neoantigen candidates. The Immunogenicity of prioritized neoantigens was evaluated by analyzing the INF-γ secretion of neoantigen-induced T cell. The antitumor immunity of neoantigen-specific Cytotoxic T cells was examined by the cytotoxicity assay.
Results
The commutative analysis and quantitative real-time PCR identified 13 candidate neoantigens of our previously established human pancreatic cancer cell line PDXPC1 which was confirm as a multi-drug resistant cancer cell line. 4 of 13 candidate neoantigens can be recognized by the immune system and induced strong neoantigen-specific T cell response. The cytotoxic activities mediated by neoantigen-specific T cells significantly inhibited the growth of PDXPC1 tumor cells. Noteworthily, T cells recognized 3 of 4 neoepitopes via the presentation of dendritic cells.
Conclusions
In conclusion, the neoantigens selected by the next generation sequencing and computational algorithm can target the tumor inhibition of pancreatic cancer, which represent a new powerful approach for multidrug resistance and suggest a general strategy for personalized cancer immunotherapy in pancreatic cancer.
Legal entity responsible for the study
The authors.
Funding
The Natural Science Foundation of Zhejiang Province.
Disclosure
All authors have declared no conflicts of interest.
224P - Associations of pre-existing cardiovascular disease (CVD) with treatment patterns and survival outcomes in patients with localized prostate cancer: A real-world, population-based study (ID 250)
- Atul Batra (New Delhi, Delhi, India)
Abstract
Background
Research has largely focused on the effect of prior androgen deprivation therapy on the subsequent risk of CVD in patients with metastatic prostate cancer. However, the impact of pre-existing CVD on localized prostate cancer treatments and outcomes is unknown. This study aimed to identify the associations of baseline CVD with treatment patterns and survival outcomes in localized prostate cancer.
Methods
We identified patients diagnosed with localized prostate cancer in a large Canadian province from 2004-2017 using the population-based registry. Administrative sources were linked to ascertain any diagnoses of CVD (including myocardial infarctions [MIs], congestive heart failure [CHF], cerebrovascular accidents [CVAs] and arrythmias [AR]) prior to the onset of prostate cancer. Logistic regression and Cox regression were used to determine the associations of baseline CVD with cancer treatments (receipt of surgery and radiotherapy) and overall survival (OS).
Results
A total of 23,670 patients were included. The median age was 65 years (interquartile range, 38-97 years). Of these, 16.4%, 71.1% and 12.5% patients had stage I, II and III prostate cancer, respectively. At the diagnosis of prostate cancer, 4860 (20.5%) had pre-existing CVD: 6.0% AR, 3.4% CVAs, 3.0% MIs, 1.8% CHF and 6.4% multiple CVDs. The Charlson comorbidity index (CCI) was 0, 1 and >1 in 55.3%, 25.4% and 19.3%. After adjusting for age, stage and CCI, pre-existing CVD was associated with a lower likelihood of surgery (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.81-0.95; P=0.001), but not radiotherapy (OR, 0.96; 95% CI, 0.88-1.04; P=0.319). Likewise, CVD was associated with worse OS, after adjusting for measured confounding variables (Table).
Hazard ratio 95% confidence interval P-value Age at diagnosis < 65 > 65 Ref 3.55 3.29-3.83 <0.001 Stage at diagnosis I II III Ref 1.33 1.52 1.18-1.51 1.30-1.77 <0.001 <0.001 Surgery No Yes Ref 0.59 0.55-0.63 <0.001 Radiotherapy No Yes Ref 0.52 0.48-0.56 <0.001 Baseline cardiovascular disease No Yes Ref 1.97 1.85-2.10 <0.001
Conclusions
One-fifth of patients with localized prostate cancer have pre-existing CVD, which was associated with a lower likelihood of surgery and worse OS. In the context of an aging general population, this may have implications for radiotherapy capacity planning as more patients are offered non-surgical therapies. Early cardio-oncology consultations may optimize the management of CVD and allow for better uptake of prostate cancer treatments.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
107P - Safety and efficacy of trifluridine/tipiracil (FTD/TPI) in previously treated metastatic colorectal cancer (mCRC): Results from the Australian cohort of the phase IIIb, international, open-label, early-access PRECONNECT study (ID 291)
- Timothy J. Price (Woodville, SA, Australia)
Abstract
Background
The PRECONNECT study assessed safety and efficacy of FTD/TPI in previously treated mCRC patients in daily practice. This analysis presents the results from the Australian patient cohort.
Methods
Enrolled patients had confirmed mCRC and ECOG PS of 0 or 1, previously treated with, or not considered candidates for available therapies. Patients received FTD/TPI (35 mg/m2, orally bid, on days 1–5 and 8–12 in a 28-day cycle) with follow-up to the end of study treatment. Withdrawal criteria included disease progression, unacceptable toxicity and commercial availability of FTD/TPI. The primary endpoint was safety; secondary endpoints were PFS and QoL.
Results
70 Australian patients from 9 centres received at least one dose at cut-off (May 2018). At baseline, median age was 61 years (range 27–77); 57.1% male; 80% Caucasian, 14.3% Asian, 1.4% Black. ECOG PS was 0/1 in 54%/44%. 60% had RAS-mutant cancers; 10% had BRAF-(V600E) mutant cancers. Primaries were left-sided in 71%, right-sided in 14% (14% not specified). Over 98% received prior fluoropyrimidine and/or oxaliplatin, irinotecan, while 91%, 36% and 0% received anti-VEGF, anti-EGFR or regorafenib respectively. Most common any-grade treatment-emergent adverse events (TEAs) were nausea (49%), asthenia/fatigue (40%), neutropenia (34%), vomiting (33%), diarrhoea (26%), Anemia (21%) and constipation (20%). Most common TEAs grade ≥3 were: neutropenia (31%), anaemia (10%), diarrhoea, nausea, vomiting, abdominal pain (3%). TEAs led to patient withdrawal in 7% and dosage reduction in 9%. Median treatment duration was 3 cycles (range 1–16). Median relative dose intensity was 92%. FTD/TPI was associated with a median PFS of 2.7 months (95% CI, 2.4–3.4) and disease control rate of 40% (95% CI, 28.47–52.41). Median time to ECOG PS decline to ³2 was 14 months. Mean QLQC30 GHS at baseline was 67.2 (±17.8) with mean change from baseline to end of therapy of -11.3 (±21.7) points.
Conclusions
Results from the Australian cohort are consistent with the global PRECONNECT population and randomised datasets in previously treated mCRC patients.
Clinical trial identification
NCT03306394.
Legal entity responsible for the study
Institut de Recherches Internationales Servier.
Funding
Institut de Recherches Internationales Servier.
Disclosure
G. Tancock: Full/Part-time employment: Servier Australia Pty. Ltd. All other authors have declared no conflicts of interest.
20P - Molecular parallelisms and divergences between human and canine cancers (ID 347)
- Sadaf Ambreen (, China)
Abstract
Background
Tumorigenesis has been widely accepted as an evolutionary process that comprises two stages of evolution between tumors and normal tissues (Stage I) and within tumors (Stage II) 1. Patterns of mutation and natural selection, the predominant evolutionary driver forces, vary at the two stages based on the evidence of low genetic convergence among different cancer cases revealed by The Cancer Genome Atlas (TCGA) data and of extremely high intra-tumor genetic diversity measured in high-density sampling studies (Ling et al. 2015; Sottoriva et al. 2015). At Stage, I, positive and negative selection may both exist but neatly counteract in absence of recombination, presenting a plausible neutrality 1, whereas non-Darwinian (neutral) selection was increasingly supported at Stage II by the high-density sampling studies and comparatively genomic and transcriptional distances among distinct normal and cancerous cell populations. Deciphering the evolutionary patterns during tumorigenesis such as selectivity or neutrality, adaptive convergence, or divergence is of both theoretical and clinical significance. Cross-species cancer genomics, independent evolution from normal tissues, provide an excellent opportunity to address this long-standing issue: Does selection drive cancer evolution along with a relatively deterministic (selectivity) or contingent (neutrality) way across species?
Methods
GATAK pipeline and Mutect2.
Results
We performed whole-genome sequencing analysis by using GATAK pipeline and Mutect2 for twenty-four dog mammary cancers and identified 47715 somatic mutations comprising 210 exonic mutations. Comparison between human and dog reveals similarities and differences in the mutation profiles across both species, in terms of the mutated driver genes and mutation number, which are likely to influence tumor behavior and response to treatments. Human breast cancer had a higher median mutation burden comparable to canine mammary cancer, in exonic regions (2.67 and 0.187 average no. of mutations per tumor per megabase (Mb), respectively).
Conclusions
Taken together, for the first time, we reported canine mammary tumors comprising mutated genes, mutation burden, mutational patterns, spectrums, and signatures at the whole genome level.
Legal entity responsible for the study
The author.
Funding
CAS-TWAS.
Disclosure
The author has declared no conflicts of interest.
262P - Correlation between phosphorylated pI3K expression, phosphorylated AKT, and phosphorylated MTOR with serum dehydrogenase lactate level in non-Hodgkin lymphoma (ID 384)
- Hary Gustian (Bandung, Indonesia)
Abstract
Background
There are 5,7 male and 3,8 female Non Hodgkin Lymphoma (NHL) patients per 100,000 populations in Indonesia. The expression of pPI3K/pAKT/pMTOR is an important expression in patients with NHL. Cascade signals from these biomarkers lead to translational regulation, cell survival, cytoskeleton organization, and ion transport. Lactate dehydrogenase (LDH) is an important marker in patients with NHL. pPI3K/pAKT/pMTOR increases gene transcription and encourages LDH proliferation.
Methods
An observational study by observing and measuring cancer cell samples from patients. Data collection method is cross sectional in which the independent and dependent variables are examined simultaneously. The expression values of pPI3K, pAKT, and pMTOR are expressed in form of histoscore. There are three range of intensity values which are one means weak, two means medium, and three mean strong, while the four distribution range are one means <20%, two means 20-50%, three means 50-80%, and four means >80%. Therefore the possible range of histoscore is from 1 to 12.
Results
The mean phosphorylated PI3K expression in NHL patients is 5,29 (2,95). The mean phosphorylated AKT expression in NHL patients is 4,71 (2,26). The mean expression of phosphorylated MTOR in NHL patients is 7,62 (1,86). The mean serum LDH level NHL patients is 428,57 (139,63) IU/L.
Conclusions
Correlation between the average expressions of pPI3K with the average level of serum LDH in NHL patients is relatively weak. The correlation between the mean of PAKT expression and the average level of LDH serum in NHL patients is classified as very weak. The correlation between mean pMTOR expression and mean serum LDH levels in NHL patients is very weak.
Legal entity responsible for the study
Andalas University, Padang.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.
440P - Blinded independent central review of oncology trials: The monitoring of readers' performance (ID 419)
- Hubert Beaumont (Valbonne, France)
Abstract
Background
For image-based evaluations, RECIST 1.1 remains the most used criteria for assessing the therapeutic response in clinical trials. The variabilities of evaluations are generally mitigated by double reading the images, with a third reader adjudicating the discrepancies. Blinded independent central review (BICR) with double read and adjudication is a complex management that needs to be closely monitored. The rate of inter-reader discrepancies is one of those metrics of choice for detecting quality issues in trials. The aim of our study was to provide reference values metrics for the monitoring of RECIST 1.1 BICR with double read plus adjudication in clinical trials.
Methods
From the list of clinical trials recorded in the Median Technologies database, we selected a subset of trials according to the following inclusion criteria: 1) Phase II and III 2) Response criteria: RECIST, 3) Trial status: completed, 4) Trial setting: central double read with adjudication, 5) Trial endpoint: Overall Response and PD and 6) Readers monitoring was enabled. For the selected trials, we analyzed, per trial and per readers, the rate of inter-reader discrepancy and the rate of readers’ endorsement by the adjudicator. We compared the discrepancy rate between the indications using Marascuillo test.
Results
Out of the 103 recorded trials, 5 conformed the inclusion criteria. Their indications were: Lung (1), Skin (1) biliary track (1), Gastric (1) and multiple (1) cancers. A total of 1561 patients (mean=312/per trial) and 5986 time points (mean=1197/per trial) were analyzed by 25 readers; 8 adjudicators were involved. Per reader, the discrepancy rate ranged from 27.4% to 68.5% (mean=50.1%) with an endorsement rate ranging from 11.5% to 91.1%. Per trial, the average discrepancy rate was 50.8% [33.0-63.8]. We found a significant difference in the rate of discrepancy per indications: Biliary (63.8%) vs Multiple cancers (33.0%) (p<0.001).
Conclusions
In BICR clinical trials with double reads and adjudication, readers’ monitoring is highly recommended. Monitoring metrics reported a wide range of discrepancy rate and of individual readers performances. Discrepancy rate and readers performances would be indication dependent.
Legal entity responsible for the study
Beaumont Hubert.
Funding
Has not received any funding.
Disclosure
H. Beaumont, A. Iannessi, J. Cillario, Y. Liu: Full/Part-time employment: Median Technologies.
443TiP - A multicenter, open-label, randomized phase II study to compare the efficacy and safety of lenvatinib in combination with ifosfamide and etoposide versus ifosfamide and etoposide in children, adolescents, and young adults with relapsed or refractory osteosarcoma (OLIE; ITCC-082) (ID 450)
- Nathalie Gaspar (Villejuif, France)
Abstract
Background
Osteosarcoma is a bone malignancy that occurs primarily in adolescents and young adults. Approximately 30% of patients (pts) with localized disease and 80% of pts with metastatic disease at diagnosis will relapse. Lenvatinib (LEN) is a multikinase inhibitor that directly inhibits tumor growth, and may increase the uptake of chemotherapy into tumor tissue by inhibiting angiogenesis. In a phase I/II study (E7080-G000-207; ITCC-050), LEN (14 mg/m2 dose) + ifosfamide (I) + etoposide (E) demonstrated a PFS rate at 4 months (PFS-4m) of 80% (95% CI: 61–91), with a manageable safety profile in pts with relapsed/refractory osteosarcoma (Gaspar ESMO 2019). This study aims to confirm the activity of LEN + I and E that was observed in the completed phase I/II study.
Trial design
This study will evaluate LEN in combination with I and E in pts (proposed N=72, with randomization of at least 32 pts < 18 yrs old) aged 2 to 25 yrs with confirmed diagnosis of osteosarcoma that is refractory or relapsed following 1-2 prior systemic treatments. Pts previously treated with I and E are eligible, except those with a history of I-related grade ≥ 3 nephrotoxicity or encephalopathy. Randomization will be stratified by time to first relapse/refractory disease (< 18 or ≥ 18 mos) and by age (< 18 or ≥ 18 yrs). Pts in arm A will receive daily oral LEN 14 mg/m2 + I 3000 mg/m2/day (IV, Days 1-3 of each cycle for ≤5 cycles) and E 100 mg/m2/day (IV, Days 1-3 of each cycle for ≤5 cycles). Pts in arm B will receive I 3000 mg/m2/day (IV, Days 1-3 of each cycle for ≤5 cycles) and E 100 mg/m2/day (IV, Days 1-3 of each cycle for ≤5 cycles). Treatment will occur in 21-day cycles. The primary objective is PFS-4m by independent imaging review (IIR) using RECIST 1.1 (% of pts alive without progressive disease at week 18). Secondary objectives include PFS, OS, ORR, safety and tolerability, LEN pharmacokinetics characterization in pts in arm A, and quality of life. Tumor assessments will be performed by the investigator every 6 wks. Disease progression must be confirmed by IIR. All AEs will be recorded.
Clinical trial identification
NCT04154189.
Editorial acknowledgement
Medical writing support was provided by Heather A. Mitchell, PhD, of Oxford PharmaGenesis, Newtown, PA and was funded by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
N. Gaspar: Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy: Ipsen. Q. Campbell-Hewson: Travel/Accommodation/Expenses: Eisai. S.S. Bielack: Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Lilly; Advisory/Consultancy: Sensorion; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Roche; Advisory/Consultancy: Boehringer Ingelheim; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Loxo. F. Bautista: Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Travel/Accommodation/Expenses: Jazz Pharmaceuticals; Advisory/Consultancy: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: EUSA Pharma; Travel/Accommodation/Expenses: Takeda. C. Meazza: Speaker Bureau/Expert testimony: Takeda. K. Janeway: Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Research grant/Funding (institution): Amgen. D.A. Morgenstern: Advisory/Consultancy: Boehringer-Ingelheim; Advisory/Consultancy: Roche; Advisory/Consultancy: Bayer; Research grant/Funding (institution): Bristol-Myers Squibb; Travel/Accommodation/Expenses: EUSA Pharma. L. Dutta, J. McKenzie, K. O'Hara, J. Huang, C.E. Okpara: Full/Part-time employment: Eisai. B. Bidadi: Full/Part-time employment: Merck & Co. Inc.; Shareholder/Stockholder/Stock options: Merck. All other authors have declared no conflicts of interest.
228P - Symptoms and impacts of metastatic castration-resistant prostate cancer (mCRPC) among Japanese patients designated to receive Ra-223 (ID 520)
- Hiroji Uemura (Yokohama, Japan)
Abstract
Background
Radium-223 (Ra-223) received regulatory approval for castration-resistant prostate cancer (CRPC) with bone metastasis in Japan in 2016. This study aimed to reveal emerging symptoms, impacts, and concerns within the Japanese patient experience of living with mCRPC and the burden of bone metastasis prior to Ra-223 treatment, through patient and physician interviews.
Methods
This non-interventional, qualitative study consisted of interviews with 23 bone metastatic CRPC patients prior to their first Ra-223 treatment cycle, and 3 treating physicians in Japan. Patients were recruited via purposive sampling. Inclusion criteria were: (1) a diagnosis of bone metastatic CRPC, and (2) designated to start receiving Ra-223 in routine clinical practice. Physicians included those who had prescribed at least one Ra-223 treatment cycle in the past 12 months and are currently prescribing Ra-223. All interview data were entered into ATLAS.ti v8.0 for coding, assessment of concept frequency, themes and saturation analysis.
Results
The patients’ mean age was 75.8 y.o., with 45% symptomatic at the time of enrolment. Forty-seven mCRPC symptoms were reported, including pain, fatigue, nocturia, muscle loss, and various side effects related to previous PC treatment and/or disease stage. Around mCRPC diagnosis, patients reported back pain (45%), hip pain (23%) and pain specifically in their bones (27%). Life impacts reported included 45 concepts, with the most frequently mentioned being worry for their disease progression and how it would impact their family and lives, the impact that mCRPC has on their daily, physical abilities (e.g. difficulty walking, muscle loss) and the impact a patients’ mCRPC has on the family and caregivers. Patients had high expectations from Ra-223 in terms of cessation of disease progression (32%) and pain alleviation (23%), but also worry about adjusting to the treatment. All 3 physicians cited the need for information sharing about Ra-223.
Conclusions
The symptoms and impacts of living with mCRPC and the associated burden of bone metastasis and skeletal-related symptoms are considerable and varied, and information sharing is key to easing concerns in utilizing Ra-223 treatment.
Legal entity responsible for the study
Bayer Yakuhin, Ltd.
Funding
Bayer Yakuhin, Ltd.
Disclosure
H. Uemura: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen Pharmaceutical; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer Yakuhin, Ltd.; Honoraria (self), Speaker Bureau/Expert testimony: Astellas Pharmaceutical; Honoraria (self), Speaker Bureau/Expert testimony: Takeda Pharmaceutical; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca Pharmaceutical. K. Akakura: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bayer Yakuhin, Ltd.; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Astellas Pharmaceutical; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Takeda Pharmaceutical; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca Pharmaceutical; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Janssen Pharmaceutical. A. Stroupe, C. Seo, A. Uzumcu, K. McCarrier: Advisory/Consultancy: Bayer Yakuhin, Ltd. D. Ledesma: Full/Part-time employment: Bayer Yakuhin, Ltd. All other authors have declared no conflicts of interest.
127P - A prospective phase II clinical trial exploring neoadjuvant immunotherapy combined with chemotherapy in resectable thoracic esophageal squamous cell cancer (TESCC) with multi-station lymph node metastases (NICE study): Preliminary results (ID 549)
- Jun Liu (Shanghai, China)
Abstract
Background
Patients (pts) with resectable TESCC with multi-station lymph node metastases derive unoptimistic overall survival benefit with neoadjuvant or postoperative adjuvant therapy. Camrelizumab (anti-PD-1) is standard of care as second-line therapy for advanced TESCC in China. We hypothesize that the addition of camrelizumab to neoadjuvant chemotherapy agents (albumin paclitaxel and carboplatin) will increase the pathological complete response (pCR) rate compared with historical controls.
Methods
This was an investigator-initiated trial for pts with newly diagnosed AJCC 8th resectable TESCC with multi-station lymph node metastases with a plan to have surgery. Pts received 2 courses of camrelizumab 200mg IV q3w added to carboplatin AUC=5 IV q3w plus albumin paclitaxel 100 mg/m2 IV qwk with surgery 4 wks after the last dose. The primary objective was pCR. Our primary endpoint will be reached if 5/52 (9.6%) planned pts have pCR.
Results
From 11/2019 to 6/2020, 11 pts were enrolled all of whom had surgery. Median age was 65 (55-72), 9.1% women, and 36.4% PD-L1 positive (≥1%, 22C3). Pre-surgical grade 3/4 toxicity occurred in 8/11pts, and treatment was delayed by an average of 5.7 days due to toxicities. Grade 3/4 toxicities were neutropenia (8/11), thrombocytopenia (2/11). All pts recovered well from pre-surgical toxicities.Our primary endpoint was met; the pCR (pT0N0M0) was achieved in 45.4% (5/11) and pT0 was 54.5% (6/11). Radiologic response rate was 90.9% (PR10,CR0). Pts with either PD-L1+ or PD-L1- had pCRs. R0 resection rate was 100% (11/11). The average intraoperative blood loss was 172ml and the average hospitalization time after operation was 9 days (7-12days).No patient developed anastomotic leak and died due to treatment-related toxicity.
Conclusions
The addition of camrelizumab to neoadjuvant chemotherapy agents (albumin paclitaxel and carboplatin) was well tolerated. The primary endpoint of pCR in at least 5/52 pts was surpassed with pCR in 5/11 pts post-surgery. The pCR was seen independent of PD-L1 score. The surprisingly good preliminary results have encouraged us to keep this phase II study ongoing.
Clinical trial identification
ChiCTR1900026240.
Legal entity responsible for the study
Shanghai Chest Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
192P - A multicenter crossover analysis of first and second-line FOLFIRINOX or gemcitabine plus nab-paclitaxel administered to pancreatic cancer patients: Results from the NAPOLEON study (ID 581)
- Kenta Nio (Fukuoka, Fukuoka, Japan)
Abstract
Background
FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) are considered standard 1st-line chemotherapy (CTx) for patients with metastatic pancreatic cancer, and reports about the effects of FFX and GnP as 2nd-line CTx have been accumulating. However, compared data of two crossover sequences and those of the comparison of the crossover sequences with others are unknown.
Methods
We investigated the efficacies of the two crossover sequences using the data of the multicenter observational study conducted in patients with CTx-naive advanced or unresectable pancreatic cancer (AUPC) treated with FFX or GnP from 14 hospitals in Japan during the period from December 2013 to June 2018. Patient characteristics and clinical outcomes including overall survival (OS), time-to-first and -second progression (TTFP/TTSP) and overall response rate (ORR) were analyzed between the two crossover groups [CG] firstly. Then, the efficacies of them were compared with non-crossover groups [NCG].
Results
Of 318 AUPC patients, 118 and 200 patients received FFX and GnP as 1st-line CTx, respectively. Of these, 91 and 100 patients received 2nd-line CTx, of which 72 (79%) and 17 (17%) patients were shifted to GnP (F-to-G) and FFX (G-to-F), respectively (p<0.01). The F-to-G group comprised more patients with higher body mass index, biliary drainage, peritoneal metastasis, and maximal tumor size of 20 mm or larger at baseline. In the two crossover sequences, there was no significant difference in the median OS (11.5 vs. 16.4 months; hazard ratio [HR] 1.25; p=0.45) between the F-to-G and G-to-F groups, respectively. No significant differences in the ORR of 1st-line (p=0.12) and 2nd-line (p=0.74) were seen. The median TTFP and TTSP were also comparable between the two groups (5.7 vs. 5.0 months; HR 0.99; p=0.97, 8.8 vs. 12.2 months; HR 1.12; 95% CI 0.67-2.02; p=0.58), respectively. Then, the median OS in the CG (n=89) was not significantly longer than that in the NCG (n=99) (11.6 vs. 12.8 months; HR 1.24; p=0.19).
Conclusions
There were no significant efficacy differences between the two CGs. The OS of CG was not statistically superior to NCG in our study.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
263P - Good response to chemotherapy in primary CNS lymphoma may not translate into significant neurocognitive improvement in comatose patients (ID 625)
- Ryan M. Lim (Singapore, Singapore)
Abstract
Background
Primary Central Nervous System Lymphoma (PCNSL) is a rare type of non-Hodgkin’s lymphoma that tends to occur in the elderly and immunocompromised patients. The mainstay of treatment is that of high-dose methotrexate-based chemotherapy. Studies suggest that radiological response to high-dose methotrexate-based chemotherapy correlates with an improvement in neurocognitive ability that remains stable on follow-up. However, no studies involving patients with extremely poor neurological status prior to the commencement of chemotherapy have been reported, and the neurological prognosis of this group of patients remains unknown.
Methods
We describe 3 patients with biopsy-proven PCNSL that had comatose neurological states (Glasgow Coma Scale, GCS of 3-5) as a result of disease progression prior to treatment. The patients all experienced a drop in GCS in the short time frame between initial presentation and the start of treatment ranging from 12 days to 6 months.
Results
Case 1 initially presented with lethargy, drowsiness and behavioural change, with disease foci in a periventricular distribution. Case 2 presented with diplopia and poor visual acuity, as a result of disease affecting the optic chiasma and brainstem. Finally, case 3 had unsteady gait, memory impairment and slow speech at diagnosis, with disease over periventricular regions involving the corpus callosum and corona radiata. All were treated with high-dose methotrexate-based chemotherapy. However, although excellent radiological responses to treatment were achieved, no meaningful neurological or cognitive recovery was documented.
Conclusions
PCNSL patients with a baseline comatose state have poor neurological prognosis even if there is excellent tumour response to chemotherapy. As it is an aggressive disease with an unpredictable clinical course, rapid detection and prompt treatment is crucial in this disease entity.
Legal entity responsible for the study
National Cancer Centre Singapore.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.