Carboplatin Etoposide Research Articles

Extensive-stage small-cell lung cancer in patients receiving atezolizumab plus carboplatin–etoposide: stratification of outcome based on a composite score that combines gene expression profiling and immune characterization of microenvironment

PurposeSmall-cell lung cancer (SCLC) is an aggressive disease with a dismal prognosis. The addition of immune checkpoints inhibitors to standard platinum-based chemotherapy in first-line setting achieves a durable benefit only...

Abstract CT090: DAREON™-7: A phase 1, open-label, dose escalation and expansion cohort trial of the delta-like ligand (DLL3)-targeting T-cell engager BI 764532, plus first-line platinum-based chemotherapy in patients with DLL3-positive (+) neuroendocrine carcinomas

Abstract Background Neuroendocrine carcinomas (NECs) have limited treatment options. DLL3 is highly expressed in NECs and is a promising treatment target. In an ongoing phase 1 trial (NCT04429087), BI 764532, a DLL3/CD3 IgG-like T-cell engager, was tolerable with clinical activity in patients with DLL3-positive (+) tumors, including those with small cell lung cancer and other NECs. Purpose DAREON™-7 (NCT06132113), a phase 1, open-label, dose-escalation (Part A) and dose-expansion (Part B) trial, aims to determine the maximum tolerated dose (MTD), recommended dose for expansion (RDE)/recommended phase 2 dose (RP2D), and the safety and efficacy of BI 764532 + platinum and etoposide in patients with DLL3+ NEC. Experimental design Part A: ~25 patients will receive intravenous BI 764532 (target dose after step-in dosing) plus carboplatin/etoposide (CE) until intolerable toxicity, or progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or for a maximum of 36 months. BI 764532 dose escalation will be guided by a Bayesian logistic regression model with overdose control. Part B: 2 cohorts (~15 patients each) will receive BI 764532 at the RDE/RP2D + CE or cisplatin/etoposide (carboplatin/etoposide or cisplatin/etoposide are the most-used standard of care [SOC] regimens). Key inclusion criteria: patients must have no prior systemic treatment for DLL3+ locally advanced or metastatic NEC (extrapulmonary or unknown primary) or large cell NEC of the lung except for 1 cycle of standard platinum/etoposide regimen as first-line treatment prior to entering the treatment period of the trial; patients with localized NEC or resectable disease who received prior adjuvant therapy can participate in the trial if they experienced a treatment-free interval of >6 months prior to the diagnosis of metastatic disease; and patients must have at least 1 measurable lesion as defined per RECIST v1.1. Patients must be adequate candidates to receive platinum/etoposide as the SOC treatment. Primary endpoints: occurrence of dose-limiting toxicities (DLTs) in the MTD evaluation (Part A) and on-treatment (Part B) periods. Secondary endpoints: occurrence of DLTs and adverse events during the on-treatment period (Part B), and efficacy measured by objective response and duration of response (Part B). Enrollment is ongoing. Citation Format: Jaume Capdevila, Timon Vandamme, Patricia Niccoli, Saori Mishima, Ken Kato, Yiyuan Ma, Ping Sun, Lijiang Geng, Ulrich M. Lauer. DAREON™-7: A phase 1, open-label, dose escalation and expansion cohort trial of the delta-like ligand (DLL3)-targeting T-cell engager BI 764532, plus first-line platinum-based chemotherapy in patients with DLL3-positive (+) neuroendocrine carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT090.

196MO Anlotinib plus etoposide/carboplatin (EC) versus placebo plus EC in first-line therapy for extensive-stage small cell lung cancer (ES-SCLC): A randomized, double-blind, parallel controlled, phase III trial (ETER 701)

196MO Anlotinib plus etoposide/carboplatin (EC) versus placebo plus EC in first-line therapy for extensive-stage small cell lung cancer (ES-SCLC): A randomized, double-blind, parallel controlled, phase III trial (ETER 701)

Efficacy of carboplatin–etoposide rechallenge after first-line chemo-immunotherapy in ES-SCLC: an international multicentric analysis

Background and objectives: Second-line treatment for small-cell lung cancer (SCLC) is primarily guided by the time elapsed since the last platinum dose. Rechallenge with carboplatin and etoposide has demonstrated superior outcomes compared to topotecan if the platinum-free interval (PFI) is longer than 90 days and is considered the standard of care. However, these findings predate the chemo-immunotherapy era. This study investigates the effectiveness of the rechallenge strategy after chemo-immunotherapy in a real-world setting. Design and methods: We retrospectively reviewed patients with the extensive stage (ES)-SCLC who received rechallenge with carboplatin and etoposide after first-line chemoimmunotherapy between September 2020 and August 2023 in nine European centres. Demographic and clinical data were collected and analysed. Results: A total of 93 patients were included. Sixty-six (71%) patients had a PFI between 3 and 6 months. Consolidation thoracic radiotherapy and prophylactic cranial irradiation had been administered in 31 (33.3%) patients and 20 (21.5%) patients, respectively. Overall response rate was 59.1%. Median progression-free survival (PFS) was 5 months (95% confidence interval (CI) 4.3–5.7) and median overall survival (OS) was 7 months (95% CI 5.7–8.3). Notably, PFS and OS were not different according to PFI (3–6 m vs > 6 m). Conclusion: Rechallenge with carboplatin and etoposide is a valid second-line option in patients with ES-SCLC whose disease progresses after first-line chemoimmunotherapy. Our analysis shows similar results to previous studies. Furthermore, outcomes were consistent across patients with different PFIs, confirming its efficacy in patients with a PFI longer than 3 months.

CTNI-72. PHASE II TRIAL OF PATHOLOGY-BASED THREE-GROUP TREATMENT STRATIFICATION FOR PATIENTS WITH CNS GERM CELL TUMORS: A LONG-TERM FOLLOW-UP STUDY

Abstract BACKGROUND Phase II clinical trial funded by Ministry of Health, Labour and Welfare from 1995 to 2003 evaluated efficacy of pathology-based three-group treatment stratification for CNS germ cell tumors (GCTs). We here present long-term follow-up results. METHODS Total 228 cases were registered. Germinoma was treated with carboplatin+etoposide (CARE) and extended-local irradiation, local irradiation was added for intermediate-prognosis-group, and poor-prognosis-group was treated with ifosfamide+cisplatin+etoposide (ICE) and whole-brain or craniospinal irradiation. RESULTS Mean/median ages at diagnosis were 16.8/16 years and female-to-male ratio was 40-188. Registry included 124 germinomas, 75 intermediate-prognosis-group cases (including 37 germinomas with STGC), 28 poor-prognosis-group cases and 1 mature teratoma. Median 222-months follow-up was conducted, and 56 recurrences and 39 deaths were recorded. 10 and 20-year event-free survival (EFS) for germinoma, intermediate and poor-prognosis-groups were 82/73%, 76/66% and 49/49%, respectively, and overall survival (OS) for each were 97/92%, 87/70% and 61/53%, respectively. Prognosis for germinoma with or without STGC was not statistically different. Basal ganglia germinoma showed significantly shorter RFS but OS was not different from other locations. Median age at death was 24 years, Time from treatment to deaths was significantly shorter for deaths due to original disease (5.7 years) than complications (14.9 years) and other causes (12.7 years) (p=0.005, 0.04, respectively). Overall survival after recurrence was clearly distinct according to the original histological groups; overall survival for germinoma, intermediate prognosis group and poor prognosis group were 94, 88 and 18% at 1 year, 91, 50 and 9% at 2 years and 88, 38 and 9 % at 3 years, respectively. CONCLUSIONS Germinoma and intermediate-prognosis-group cases showed long-term survival for approximately 90%, while more intensive treatment would be necessitated for poor-prognosis-group. Long-term survivors often required hormonal supplementation, and increasing frequency of treatment-related complications was observed. There is no end of outpatient follow-up for CNS GCT patients.

The Impact of Surgery & Chemo in Treating Sex Cord-Stromal Tumors

The Impact of Surgery & Chemo in Treating Sex Cord-Stromal Tumors

A study on oligo-progression after durvalumab plus platinum-etoposide for ES-SCLC.

e20642 Background: Chemotherapy plus immune-checkpoint inhibitor(ICI) therapy is the standard of care for untreated extensive-stage small cell lung cancer(ES-SCLC), but the pattern of progression has not been fully investigated. It is known that a certain percentage of patients with ES-SCLC have Oligo-Progression, and ICI treatment can be continued with the addition of local therapy. This is great significance in the current situation where post-treatment is limited. Methods: We performed a retrospective analysis of patients with ES-SCLC treated with durvalumab plus platinum–etoposide regimen from September 2020 to January 2023 in our institution. Results: Forty patients were included, median age was 68 years (range 45-89), 32 (80%) patients were male and 8 (20%) patients were female, ECOG-PS was 0 or 1 in 25 (63%) patients, 2 or 3 in 15 (38%) patients, 38 (95%) patients had a smoking history, 39 (98%) patients were Stage IV, and the regimens were durvalumab plus cisplatin–etoposide in 15 (38%) patients and durvalumab plus carboplatin–etoposide in 25 (63%) patients. The median PFS was 5.9 months (95% CI: 3.8-8.0) and the median OS was 25.4 months (95% CI: 6.0-44.8). 14(35%) patients were still on treatment. Of the 17 (43%) patients with confirmed RECIST-PD, 4 patients had Oligo-Progression. All of them continued ICI treatment with additional radiation therapy. Two patients are continuing ICI treatment. Two patients with second recurrence, and the time from RECIST-PD to second recurrence was 5 months and 18 months, respectively. Conclusions: Among patients with RECIST-PD after durvalumab plus Platinum–Etoposide for ES-SCLC, Oligo-Progression was observed in 24%, and the strategy of continued ICI treatment in addition to local therapy may be promising.

Effectiveness and safety of first-line immune checkpoint inhibitors for patients with extensive-stage small cell lung carcinoma: A systematic review and network meta-analysis

ObjectiveIn recent years, the introduction of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of extensive-stage small cell lung carcinoma (ES-SCLC), but the optimal combination of ICI and standard chemotherapy strategy is yet to be established. The aim of this network meta-analysis (NMA) was to identify which first-line combination strategy is optimal for patients with ES-SCLC. MethodsPubMed, Embase, Cochrane Library, and the proceedings of international conferences, including American Society of Clinical Oncology and European Society for Medical Oncology meetings, were searched for randomized controlled trials (RCTs) published through October 31, 2022. The collected primary outcomes were overall survival (OS), progression-free survival (PFS), and grade 3–5 treatment-related adverse events (TRAEs). ResultsOur NMA study included six phase 3 and three phase 2 RCTs including 4037 patients and 10 first-line regimens. Regarding effectiveness, the addition of programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors to standard chemotherapy provided greater efficacy than chemotherapy alone. However, cytotoxic T lymphocyte-associated antigen-4 inhibitors were not associated with satisfactory prognoses. Serplulimab plus carboplatin–etoposide (vs. standard chemotherapy, hazard ratio [HR] = 0.63; 95% CI = 0.49–0.82) and nivolumab plus platinum–etoposide (HR = 0.65; 95% confidence interval [CI] = 0.46–0.91) displayed the greatest benefit regarding OS. In terms of PFS, serplulimab plus carboplatin–etoposide yielded the best benefit of all treatments (HR = 0.48; 95% CI = 0.39–0.6). The combination of ICIs and chemotherapy caused more toxicity in general, but durvalumab plus platinum–etoposide (odds ratio [OR] = 0.98; 95% CI = 0.68–1.4), atezolizumab plus carboplatin–etoposide (OR = 1.04; 95% CI = 0.68–1.6), and adebrelimab plus platinum–etoposide (OR = 1.02; 95% CI = 0.52–2) displayed similar safety as standard chemotherapy. Subgroup analysis by race illustrated that serplulimab plus carboplatin–etoposide was associated with the best OS in Asian patients. And in non-Asian patients, the combination of PD-1/PD-L1 inhibitors and chemotherapy (pembrolizumab plus platinum–etoposide, durvalumab plus platinum–etoposide, and durvalumab and tremelimumab plus platinum–etoposide) displayed superiority to standard chemotherapy. ConclusionsThe results of our NMA study suggested that serplulimab plus carboplatin–etoposide and nivolumab plus platinum–etoposide are associated with the best OS as first-line treatments for patients with ES-SCLC. Serplulimab plus carboplatin–etoposide was associated with the best PFS. In Asian patients, serplulimab plus carboplatin–etoposide had the best OS. Systematic review registrationThis study is registered with PROSPERO, number CRD42022345850.

The predictive value of YAP-1 and POU2F3 for the efficacy of immuno-chemotherapy in extensive-stage SCLC patients

IntroductionRecently, several clinical trials of immunotherapy for extensive-stage small-cell lung cancer (ES-SCLC) have shown limited benefits because of unselected patients. Thus, we aimed to explore whether YES-associated protein 1 (YAP-1) and POU domain class 2 transcription factor 3 (POU2F3) could identify SCLC patients with durable benefits from immunotherapy as potential biomarkers. MethodsWe performed IHC of YAP-1 and POU2F3, and RNA-seq on tissues of ES- SCLC patients. An open-source plugin based on IHC-profiler was conducted to calculate the expression levels of YAP-1 and POU2F3. ResultsPatients with ES-SCLC were retrospectively investigated in the Guangdong Provincial People's Hospital from January 2018 to July 2021, and 21 patients whoever received atezolizumab plus etoposide/carboplatin (ECT) regimen also had tissue samples reachable. The median IHC-score of YAP-1 in responders (CR/PR patients) was significantly lower than in nonresponders (SD/PD patients) at 13.97 (95% CI: 8.97–16.30) versus 23.72 (95% CI: 8.13–75.40). The IHC-score of YAP-1 and PFS showed a negative correlation by Spearman (r=-0.496). However, POU2F3 did not show a correlation with efficacy. Besides, patients with YAP-1 high expression had IL6, MYCN, and MYCT1 upregulated, while analysis of immune cell infiltration only showed that M0 macrophages were significantly higher. ConclusionsThe expression of YAP-1 negatively correlated with the efficacy of ECT in ES-SCLC patients while POU2F3 did not reveal the predictive value. However, prospective investigations with a large sample size are needed.

PEDT-10 PHASE II TRIAL OF PATHOLOGY-BASED THREE-GROUP TREATMENT STRATIFICATION FOR PATIENTS WITH CNS GERM CELL TUMORS: A LONG-TERM FOLLOW-UP STUDY

Abstract Background Phase II clinical trial funded by Ministry of Health, Labour and Welfare from 1995 to 2003 evaluated efficacy of pathology-based three-group treatment stratification for CNS germ cell tumors (GCTs). We here present long-term follow-up results. Methods Total 228 cases were registered. Germinoma was treated with carboplatin+etoposide (CARE) and extended-local irradiation, local irradiation was added for intermediate-prognosis-group, and poor-prognosis-group was treated with ifosfamide+cisplatin+etoposide (ICE) and whole-brain or craniospinal irradiation. Results Mean/median ages at diagnosis were 16.8/16 years and female-to-male ratio was 40-188. Registry included 123 germinomas, 76 intermediate-prognosis-group cases (including 38 germinoma with STGC), 28 poor-prognosis-group cases and 1 mature teratoma. Median 222-months follow-up was conducted, and 56 recurrences and 39 deaths were recorded. 10 and 20-year recurrence-free survival (RFS) for germinoma, intermediate and poor-prognosis-groups were 84/79%, 83/76% and 59/59%, respectively, and overall survival (OS) for each were 97/91%, 92/85% and 57/53%, respectively. Prognosis for germinoma with or without STGC was the same. Basal ganglia germinoma showed significantly shorter RFS but OS was not different from other locations. Median age at death was 24 years, and ages were significantly different depending on causes, such as disease-related (14 years on average) and complications (29 years). OS after recurrence at 5/10/20 years were 64/62/48%.Hormonal supplementation was seen in 82% for neurohypophyseal cases and antidiuretic hormone supplementation was most frequent (82%). Among available cases, 20-out-of-155 cases showed neoplastic/vascular complications, among which cavernous malformation was the most (n=9). Median period until complication presentation was 235 months, and the rate at 20 years was 11%. Conclusions Germinoma and intermediate-prognosis-group cases showed long-term survival for approximately 90%, while more intensive treatment would be necessitated for poor-prognosis-group. Long-term survivors often required hormonal supplementation, and increasing frequency of treatment-related complications was observed. There is no end of outpatient follow-up for CNS GCT patients.

SKYSCRAPER-02: Primary results of a phase III, randomized, double-blind, placebo-controlled study of atezolizumab (atezo) + carboplatin + etoposide (CE) with or without tiragolumab (tira) in patients (pts) with untreated extensive-stage small cell lung cancer (ES-SCLC).

LBA8507 Background: Atezo, in combination with CE, was the first cancer immunotherapy approved for 1L treatment of ES-SCLC. However, most pts eventually experience disease progression. TIGIT is a novel inhibitory immune checkpoint present on activated T cells and NK cells. Tira (anti-TIGIT) may synergise with other immunotherapies, such as PD-L1/PD-1 inhibitors, and further amplify the immune response to improve clinical outcomes. SKYSCRAPER-02 (NCT04256421) evaluates whether the antitumor effect and survival benefits of the combination of atezo + CE could be enhanced by adding tira in pts with ES-SCLC. Methods: Eligible pts with untreated ES-SCLC (asymptomatic treated or untreated brain metastases [BM] permitted) were randomized 1:1 to receive induction tira 600 mg IV or placebo (pbo) combined with atezo 1200 mg IV + CE for 4 x 21-day cycles followed by maintenance tira or placebo combined with atezo every 3 weeks until disease progression or loss of clinical benefit. Stratification factors include ECOG PS (0 vs 1); presence/history of BM (yes vs no); LDH (≤upper limit of normal [ULN] vs >ULN). Co-primary endpoints were investigator-assessed PFS and OS in all randomized pts without the history/presence of BM at baseline (primary analysis set [PAS]). Additional endpoints include PFS and OS in all randomized pts regardless of BM status (full analysis set [FAS]), objective response rate, duration of response, and safety. Results: A total of 490 patients were randomized (tira + atezo + CE, n=243; pbo + atezo + CE, n=247). As of 6 Feb 2022, median duration of follow-up was 13.9 months (mo); data represent final analysis for PFS and interim analysis for OS. In the PAS, no additional benefit was seen for tira + atezo + CE in PFS or OS compared with pbo + atezo + CE (Table). PFS and OS in the FAS were consistent with those observed in the PAS (Table). Grade 3/4 TRAEs occurred in 52.3% (tira + atezo + CE) and 55.7% (pbo + atezo + CE) and Grade 5 TRAEs occurred in 0.4% (tira + atezo + CE) and 2.0% (pbo + atezo + CE). TRAEs leading to any treatment discontinuation occurred in 5.0% and 5.3% with tira + atezo + CE and pbo + atezo + CE, respectively. Conclusions: The addition of tira to atezo + CE did not provide benefit over atezo + CE in pts with untreated ES-SCLC with or without BM. The combination was well tolerated, and no new safety signals were identified. The study will continue to planned final OS analysis. Clinical trial information: NCT04256421. [Table: see text]

The Change of Soluble Programmed Death Ligand 1 (sPD-L1) in Plasma of Small Cell Lung Cancer and Its Clinical Significance.

Background soluble programmed death-ligand 1 (sPD-L1) expression in lung squamous cell carcinoma and lung adenocarcinoma is associated with disease progression, and sPD-L1 expression in small cell lung cancer (SCLC) may have similar manifestations and become a potential marker for treatment. The purpose of this study was to observe the changes of plasma sPD-L1 expression in SCLC patients. Methods. 90 patients diagnosed with SCLC from January 2019 to November 2020 were selected as the test group, including 72 males and 18 women, 58.7 ± 6.6 years; 30 healthy subjects were selected from the physical examination center, including 18 males, 12 females, and 60.3 ± 7.0 years. There were no statistical difference in sex and age factors between the trial and control groups (p > 0.05). Selected SCLC used chemotherapy regimen: cisplatin + etoposide (EP), carboplatin + etoposide (CE), and SCLC group were divided into three subgroups of disease progression group, partial remission group, and disease stability group according to the treatment effect. Comparison of the differences in sPD-L1 expression content between the experimental and control populations. Plasma sPD-L1 levels were dynamically monitored pre- and posttreatment in 90 patients with small-cell lung cancer and were associated with efficacy among subgroups. Meanwhile, the risk factors for patient sPD-L1 expression content were analyzed by logistic regression. Results. Plasma sPD-L1 levels were higher in the SCLC group than in the healthy people group (t = 7.40, p < 0.01). In the disease progression group of the SCLC group, sPD-L1 levels were decreased in the SCLC group, sPD-L1 in some remission group was increased after treatment, and sPD-L1 levels in the disease-stable group (p > 0.05). Multivariate logistic regression analysis showed that factors promoting increased sPD-L1 expression in SCLC patients included increased smoking, brain metastasis, and ProGRP expression (both p values < 0.05). Conclusion. (1) Higher peripheral sPD-L1 expression in SCLC patients than in healthy patients, and the expression levels were closely related to efficacy. (2) Dynamic changes in s PD-L1 were correlated with clinical efficacy. (3) The progression of sPD-L1 and ProGRP in SCLC patients showed the same extent during remission and stabilization, suggesting the effect of s PD-L1 in the evaluation of SCLC tumors and the reflection of the tumor marker ProGRP.

Small cell lung cancer: Real-world data from two institutions in Lebanon for patients receiving carboplatin etoposide or atezolizumab in first line of treatment.

e20578 Background: Small-cell lung cancer (SCLC), accounts for approximately 15% to 17% of all diagnosed lung cancers. It is an aggressive high-grade neuroendocrine carcinoma, diagnosed during advanced stages in the majority of patients. Despite the fact that first line treatment provides response rates of up to 80%, the majority of patients relapse within 6 months after completion of initial treatment. Few advances have been made in the management of recurrent disease and treatments patterns are poor and limited in each line of the disease. The aim of this study is to present real world data regards survival outcomes such as progression free survival and overall survival in SCLC patients receiving carboplatine etoposide or tecentriq carboplatin etoposide regimens as first line of treatment. Methods: This is a retrospective (descriptive) study on 56 patients aged ≥ 18 years and with confirmed histological SCLC. Patients with extensive stage of SCLC were enrolled in this cohort study from 2 health institutions in Lebanon from July 2007 to December 2019 and followed up until progression or death. Primary end points were overall survival (time from randomization to death from any cause) and progression free survival at 6 and 12 months (time from randomization to disease progression). Secondary endpoints included objective response rate and the duration of response. Exploratory analyses included the assessment of survival outcomes of each type of treatment according to liver and brain metastasis. Results: Overall, 56 SCLC patients, diagnosed between 2003 and 2019, were observed (age &lt;65: (27.0%, 10 patients); ≥65 (73.0%, 41 patients)). Most often prescribed treatment were etoposide-carboplatyl (80.8%, 42 patients) and atezolizumab (19.2%10 patients). Regarding metastasis at diagnosis, liver and brain metastasis were respectively (26.8%, 11 patients) and (17.1%, 7 patients). 27patients (71.1%) were alive at 6 months without progressive disease and 13 patients (34.21 %) alive at 12 months without PD. Median progression free survival incidence since diagnosis was 8.8 months. Overall survival was 10.86 months. Objective response rate after first line was 84.2%. In a cox regression analysis, liver metastasis, brain metastasis, survival at 6 or 12 months without progressive disease did not decrease significantly PFS or OS since diagnosis. Conclusions: To our knowledge, this is the first real world clinical data on SCLC in Lebanon. This study showed limited treatment options and short survival outcomes with PFS= 8.8months and OS= 10.86 months respectively for carboplatin etoposide regimen and tecentriq carboplatin etoposide regimen. There is an essential needs for clinical comparative studies in real world practicing between treatments at each line, specially for novel treatment like atezolizumab that may present new hope and directions for SCLC.

An institutional evaluation of the safety and efficacy of same-day administration of pegfilgrastim in patients receiving chemotherapy for lung cancer.

e18591 Background: Pegfilgrastim is recommended to be administered 24 hours after myelosuppressive chemotherapy (CTX) as prophylaxis for chemotherapy-induced (febrile) neutropenia (CIN/FN). Recent studies have yielded equivocal data on same day versus next day administration of pegfilgrastim. There has been limited real world evidence addressing lung cancer (LC) patients and the use of same day pegfilgrastim. We evaluated our own institutional data on the safety of same day pegfilgrastim administration in LC patients. Methods: A retrospective chart review was performed by searching electronic health records using ICD-9 and ICD-10 codes corresponding with a lung cancer diagnosis between November 1, 2013 and August 31, 2018 at The University of Arizona Cancer Center (UACC). Patients included in the study were 18 years of age or older, diagnosed with biopsy-confirmed lung cancer, treated at UACC, and receiving chemotherapy and pegfilgrastim on the same day. The outcomes of interest included FN incidence after the first cycle and across all cycles of CTX, CIN grade 3/4 and CTX dose delays or hospitalizations due to CIN/FN after first cycle and across all cycles of CTX. Results: 1,181 patient records were reviewed and 114 patients met the inclusion criteria; 87 (76%) patients had non-small cell LC and 27 (24%) patients had small cell LC. The median age was 68 years, 52% of patients had cancer stage of 3 to 4, and 63% of patients had 0-1 ECOG status. The FN risk assessment was mild in 72% of patients. The mean (SD) of baseline absolute neutrophil count was 5.68 (3.09). In total 384 CTX cycles were received. The table shows the results of all intended outcomes. One patient experienced FN after the first cycle of CTX of irinotecan and 5 patients developed 6 FN episodes across all cycles; 2 patients were on carboplatin etoposide; 1 patient on cisplatin etoposide; 1 patient on vinorelbine and 1 patient was on pemetrexed and then on irinotecan CTX when the two FN episodes were developed. Conclusions: This study showing that same day administration of pegfilgrastim was as effective as next day administration in LC patients, without warranting any concerns for febrile neutropenia or delayed engraftment. Utilization of same day pegfilgrastim, in light of biosimilars and COVID, provides a unique opportunity for cancer care without concerns for FN as stated in previous studies.[Table: see text]

Treatment of advanced small cell lung cancer. Clinical case and literature review

Lung cancer is one of the most common tumors in humans. The incidence is in one of the leading positions. In 2019 1327 patients with this pathology were identified in the Republic of Bashkortostan. Of these, with stage III of the disease 28.7%, with stage IV 45.8%, which is higher. Small cell lung cancer (SCLC) is one of the most prognostically unfavorable malignant tumors in humans. About 15% of lung tumors are SCLC. The first combination for the treatment of advanced SCLC after etoposide and platinum preparations was the combination of the etoposide + carboplatin (EP) regimen with atezolizumab. In the IMpower133 study, after a median follow-up of 13.9 months. median overall survival in the atezolizumab group was 12.3 months, and in the placebo group 10.3 months. In clinical observation, the effectiveness of the combination of the EP regimen with atezolizumab has been demonstrated. A patient with SCLC received 4 courses of EP therapy with atezolizumab and 14 injections of atezolizumab. The partial response achieved is retained. Case study efficacy and satisfactory safety profile of the combination of atezolizumab and the EP regimen.

Melphalan, Etoposide, and Carboplatin Megatherapy with Autologous Stem Cell Transplantation in Children with Relapsing or Therapy-Resistant Extracranial Germ-Cell Tumors-A Retrospective Analysis.

Simple SummaryGerm cell tumors (GCTs) are malignancies derived from germ cells that originate in gonads or extragonadal localizations. They are considered highly curable in both children and adults even if distant metastases are present, but therapy-resistant or relapsing patients have a worse prognosis. The aim of our retrospective study was to analyze the outcome of 18 children with GCT treated with melphalan–etoposide–carboplatin high-dose chemotherapy and autologous stem cell transplantation. To date, this is one of the largest reported pediatric cohorts of GCT patients treated with megatherapy. We observed high survival rates—a five-year overall survival of 76%, and event-free survival of 70.8% without therapy-associated mortality. We concluded that this megatherapy protocol is feasible in heavily pretreated children, but the issue of precise indications for high dose chemotherapy (HDCT) is evident and must be answered in a well-designed controlled study to avoid unnecessary overtreatment.Pediatric germ cell tumors (GCTs) are a group of chemosensitive malignancies with a 90% curability rate. We report a series of children with relapsing or therapy-resistant GCT treated with melphalan–etoposide–carboplatin high-dose chemotherapy (HDCT) and autologous stem cell transplantation. This consisted of 18 children, either with GCTs after relapse (nine patients) or with an unsatisfactory response to first-line chemotherapy (nine patients), who underwent HDCT. The HDCT regimens MEC1 (carboplatin 1500 mg/m2, etoposide 1800 mg/m2, and melphalan 140 mg/m2) and MEC2 (carboplatin 800 mg/m2, etoposide 800 mg/m2, and melphalan 140 mg/m2) were each used in nine patients. The median observation time was 81 months, the 5-year overall survival (OS) was 76%, and the event-free survival (EFS) was 70.8%. Non-relapse mortality was 0%, and four patients died after HDCT due to progression of the malignancy. No difference in OS or EFS was noted between the MEC1 and MEC2 protocols. The 5-year OS and 5-year EFS were higher in children treated with autologous stem cell transplantation before the age of four years. The presence of metastatic disease or time of HDCT consolidation during first/subsequent line chemotherapy did not affect patient survival. The melphalan–etoposide–carboplatin protocol is feasible in pediatric GCT, but is associated with potentially life-threatening complications. In conclusion, the use of HDCT must be examined in well-designed clinical trials, and the identification of patients who can benefit from this approach is critical to avoid overtreatment.

EPEN-06. CHEMOTHERAPY OF RECURRENT EPENDYMOMA: LONG-TERM RESPONSE ONLY IN FEW CASES

INTRODUCTIONThe efficacy of chemotherapy in recurrent ependymoma is unclear. We present results from the German HIT-REZ-studies.METHODS137 patients were analyzed regarding the treatment with chemotherapy at first recurrence, the time from first relapse to progression (PFS) and to either time-point of death or last follow-up (OS). Tumor response evaluation was based on MRI and clinically; molecular data was available in 80.RESULTSIn our cohort, 96 patients (20 supratentorial, 73 infratentorial, 3 spinal) received chemotherapy during first recurrence: 49 (51.0%) temozolomide (TMZ) monotherapy, 12 (12.5%) HIT-SKK regime, 9 (9.4%) carboplatin/etoposide (CE) and 26 (27.1%) other combinations. In 19.8% (26.5% in TMZ), chemotherapy was administered prior to surgery (neoadjuvant), which resulted in tumor progression in 78% (85% in TMZ). Gross-total resection was achieved in 86% without neoadjuvant chemotherapy and in 74% (69% in TMZ) with neoadjuvant treatment. Switching to trofosfamide/etoposide (TE) after surgery and unresponsiveness to TMZ showed further progression in all cases of tumor-residuum after surgery. Regarding 1-year-PFS, treatment with HIT-SKK (50.0%±14.4%) or CE (55.6%±16.6%) was advantageous over TMZ (30.2%±6.7%). However, 5-y-OS was lower in CE (19.0% ±16.8%) than in TMZ (39.8%±7.7%) and HIT-SKK (42.9%±8.7%). Long-term control was seen in individual cases of TMZ, HIT-SKK and CE, with TMZ providing longest response of 72 months.CONCLUSIONNeoadjuvant TMZ has no significant advantage regarding PFS. However, in few cases chemotherapy prevented progression after incomplete resection. Difficulties in response evaluation and variability in therapies hinder conclusions. Supported by the German Children’s Cancer Foundation

High Dose Chemotherapy with Autologous Stem Cell Transplantation in Hepatoblastoma does not Improve Outcome. Results of the GPOH Study HB99.

The purpose of the German HB99 trial (1999-2008) for hepatoblastoma (HB), was primarily to analyse the effect of high dose (HD) chemotherapy with carboplatin/etoposide (CE) in high risk (HR) patients with extended tumors, vessel involvement, extrahepatic tumor or distant metastases. In standard risk (SR) patients the effect of treatment reduction was analysed. HR patients received 2 cycles CE at conventional dose, followed by 2 at HD with subsequent autologous stem cell transplantation before delayed surgery. SR patients received 3-4 cycles of ifosfamide, cisplatin and doxorubicin (IPA) and delayed surgery. Analysis was on an intention to treat basis including resection rate, AFP decline, event free survival (EFS) and overall survival (OS). The patients with HD therapy were additionally analysed on an "as treated" basis. The results were compared to historical/published data. Of the 142 patients, the 5-y OS was 58% for the 57 HR patients and 94% for the 85 SR patients. The AFP decline after 2 cycles CE was ≥ 50% in > 90% of the patients. 12/18 (67%) patients treated with HD therapy showed an AFP decline after the first cycle (as treated). Tumor resection was possible in 89% of the patients. The median FU was 7.4 years. Late deaths occurred in 4 patients. Use of HD chemotherapy for HB did not improve patient outcomes, compared to contemporaneous and more recent trials (SIOPEL 4 trial). Reduction of therapy in SR patients was possible without worsening of results compared to previous trials. The tumor response to CE was good. CE can therefore be considered for relapse patients.

Tandem high-dose chemotherapy with topotecan-thiotepa-carboplatin and melphalan-etoposide-carboplatin regimens for pediatric high-risk brain tumors.

High-dose chemotherapy (HDC) and autologous stem-cell transplantation (auto-SCT) are used to improve the survival of children with high-risk brain tumors who have a poor outcome with the standard treatment. This study aims to evaluate the outcome of HDC/auto-SCT with topotecan-thiotepa-carboplatin and melphalan-etoposide-carboplatin (TTC/MEC) regimens in pediatric brain tumors. We retrospectively analyzed the data of 33 children (median age 6years) who underwent HDC/auto-SCT (18 tandem and 15 single) with uniform conditioning regimens. Eleven patients aged < 3years at diagnosis were eligible for HDC/auto-SCT to avoid or defer radiotherapy. In addition, nine patients with high-risk medulloblastoma (presence of metastasis and/or postoperative residual tumor ≥ 1.5cm2), eight with other high-risk brain tumor (six CNS primitive neuroectodermal tumor, one CNS atypical teratoid/rhabdoid tumor, and one pineoblastoma), and five with relapsed brain tumors were enrolled. There were three toxic deaths, and two of which were due to pulmonary complications. The main reason for not performing tandem auto-SCT was due to toxicities and patient refusal. The event-free survival (EFS) and overall survival (OS) rates of all patients were 59.4% and 80.0% at a median follow-up with 49.1months from the first HDC/auto-SCT, respectively. The EFS/OS rates of patients aged < 3years at diagnosis, high-risk medulloblastoma, other high-risk brain tumor, and relapsed tumors were 50.0/81.8%, 87.5/85.7%, 66.7/88.9%, and 20.0/60.0%, respectively. Although tandem HDC/auto-SCT with TTC/MEC regimens showed promising survival rates, treatment modifications are warranted to reduce toxicities. The survival rates with relapsed brain tumors were unsatisfactory despite HDC/auto-SCT, and further study is needed.

Cisplatin or carboplatin? Neutrophil to lymphocyte ratio may serve as a useful factor in small cell lung cancer therapy selection.

The present study aimed to investigate the significance of the neutrophil to lymphocyte ratio (NLR) in peripheral blood of patients with small cell lung cancer (SCLC) when selecting a first-line treatment. A total of 73 patients with SCLC who had complete clinical data and sought treatment at Fujian Medical University Union Hospital between January 2014 and May 2016 were included. Data were retrospectively analyzed, utilizing a receiver operating characteristic curve to determine the NLR cut-off value. Out of the 73 patients, 39 were classified as high-NLR (NLR ≥3.80) and 34 as low-NLR (NLR <3.80). Compared with the high-NLR group, patients in the low-NLR group had a longer progression free survival (PFS); however, there was no statistically significant difference in overall survival (OS) time. Patients with a high NLR had a significantly longer PFS (P=0.021) and OS time (P=0.042) when treated with a etoposide/cisplatin (EP) therapy regimen, compared with those treated with etoposide/carboplatin (EC). PFS was the longest in the high-NLR patients with limited stage (LS; P=0.002). Among the patients receiving the EC regimen, the PFS of the low-NLR group was significantly longer compared with the high-NLR group (P=0.003). Patients in the low-NLR group who received thoracic radiotherapy had a longer PFS (P=0.011), when comparing patients in the low-NLR group who did not receive thoracic radiotherapy, and within this group the therapeutic effect of radiation was the greatest in LS patients. Compared with the high-NLR group, the low-NLR group patients who received cranial radiotherapy had a significantly longer PFS (P=0.039). For the initial evaluation of patients with SCLC, pre-treatment NLR may be of significance for selecting first-line chemotherapy agents. As the present study was retrospective and investigated a limited number of patients, further research and prospective studies are warranted.