Background

In Egypt, lung cancer is the most lethal malignancy. Most patients present with locally advanced or metastatic disease. The aim of the study is to review all demographic and clinic-pathological features of Non- Small Cell Lung Cancer (NSCLC) patients, treatment lines received and then evaluate the discriminatory ability of the new 8th American Joint Committee on Cancer (AJCC)/International Union for Cancer Control (UICC) staging system edition T category, M category and compare it with the 7th edition.

Methods

In this retrospective population-based cohort, data on patient characteristics, tumor characteristics, diagnostic tools used to reach a diagnosis and treatment modalities administered has been collected from the archive of Alexandria Clinical Oncology Department. The study participants included all NSCLC patients who fulfilled the inclusion criteria.

Results

222 patients fulfilled the criteria to be included in the study.192 patients in the 7th edition and 30 in the 8th edition. Male predominance (82.8%) in 7th edition and (80%) in 8th edition. The mean age of diagnosis is 58.8years (ranging from 23 to 84) in the 7th edition and 65.0years (ranging from 40 to 82) in the 8th edition. Surgery was done on 8.1%, concomittant chemo-radiotherapy on 9.9% cases overall. The 7th edition 87.5% and 76.7% of patients received chemotherapy. When we used tumor size to categorize the patients, according to the 7th edition AJCC TNM stage, T1a and T1b 0 patients, T2a 15 (7.8%) patients, T2b 18(9.4%) patients, T3 23(12%) patients, T4 136(70.8%) patients. According to the 8th edition of AJCC TNM stage, T1a,T1b, T1c, T2a 0 patients, T2b 5 patients (16.7%) T3 7 patients (23.3%) T4 18 patients (60%). We were able to draw that survival time decreases as the pathological stage progresses. The 8th edition was shown to be more discriminatory in showing this. The median PFS was 6months between the first line(cisplatin based) P value 0.114 and second line of chemotherapy. Factors such as N stage (P < 0.001), pleural invasion and vessel invasion were associated significantly with DFS.

Conclusions

The 8th edition of AJCC/TNM staging seems to be more superior than the 7th edition in both treatment guidelines and predicting survival.

Legal entity responsible for the study

University of Alexandria.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

TET are rare malignancies that range from indolent thymoma A to aggressive thymic carcinomas (TC). TET are associated with autoimmune disorders (AID) in up to 30% of patients (pts). The pleura is the main metastatic site. Brain metastases are extremely infrequent for TET and they have been only described in case reports.

Methods

RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French nationwide network mandated to systematically discuss every case of TET. The database, hosted by IFCT (Intergroupe Francophone de Cancérologie Thoracique), prospectively includes all consecutive pts with a diagnosis of TET discussed in RYTHMIC national or regional tumor boards. We analysed epidemiologic, clinical and pathological characteristics of pts with TET and CNS metastasis during cancer history.

Results

From January 2012 to December 2019, 2909 pts were included in the database, including 248 TC (8.5%). The median age at diagnosis was 63.5 (range 9 to 91). There were 14 pts with CNS metastases during cancer history; 5 (35.7%) at diagnosis, of them 3 with isolated CNS lesions (retro-orbital lesion for the 1^st, a cerebellum nodule for the 2^nd and multiple lesions for the 3^rd) and 2 with extracerebral lesions. Among the 14 pts, half were men. None of the pts reported any AID. 12/14 (85.8%) pts were diagnosed of TC and 2 (14.2%) of a thymoma A and B3. A surgical biopsy was performed and the histological subtype for non-TC tumours was centrally confirmed. In 9 (64.3%) pts, CNS was a recurrence event with a median of 9 months (95%CI 5.5–12.55) after diagnosis. Median follow-up was 28 months. Median overall survival (OS) was 22 months (95%CI 9.8–34.2). OS tend to be better when CNS were found at diagnosis vs. relapse (not reached vs. 17 moths) and, median progression free survival (PFS) was 13 vs. 8 months respectively. No differences between histological subtypes (9 vs. 8 months for no TC vs. TC respectively). No greater risk of recurrence was seen for CNS metastases found at diagnosis (OR = 0.6, 95%CI. 0.29–1.22; p = 0.04).

Conclusions

The prevalence of CNS disease was extremely rare in our cohort (0.48%). CNS metastases have been reported at diagnosis and at progression mainly for thymic carcinoma in which the incidence was 4.9%.

Legal entity responsible for the study

RYTHMIC network/IFCT.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

ES SCLC is an aggressive disease with relapses despite initial response to chemotherapy. In the CC-90011-SCLC-001 study, CC-90011 in combination with EP was well-tolerated in 1L ES SCLC pts. Here, we report updated data for CC-90011 + EP and results with CC-90011 + EC.

Methods

CC-90011-SCLC-001 (NCT03850067) is a phase Ib study of CC-90011 + EP and CC-90011 + EC in 1L ES SCLC. In the chemotherapy phase, pts received EP or EC + escalating doses of CC–90011 (20, 40, 60 mg) on days 1 and 8 of a 21-d cycle for 4–6 cycles. Responders entered a maintenance phase and received CC-90011 60 mg once/wk in a 28-d cycle. Primary endpoints were safety, tolerability, and recommended phase II dose (RP2D). Other endpoints were efficacy (RECIST 1.1 criteria), pharmacokinetics (PK), and pharmacodynamics (PD).

Results

As of 11 Sept 2020, 19 pts received CC-90011 at 20 (n = 8), 40 (n = 7), and 60 mg (n = 4) + EP and 5 received CC-90011 at 20 (n = 3) and 40 mg (n = 2) + EC. Of the 19 pts (CC-90011 + EP) and 5 pts (CC-90011 + EC), 12 and 3 received CC-90011 maintenance for a median of 7.5 and 4.0 wk; 6 and 1 pts discontinued treatment due to adverse events (AEs; n = 4), withdrawal by patient (n = 1), or progressive disease (n = 2). The RP2D of CC-90011 was established as 40 mg with EP and the evaluation of the RP2D of CC-90011 with EC is ongoing. Four pts had dose-limiting toxicity, 1 with grade 3 neutropenia at CC-90011 20 mg + EP, 2 with grade 2–4 thrombocytopenia or grade 4 neutropenia/febrile neutropenia at CC-90011 60 mg + EP, and 1 with grade 4 thrombocytopenia at CC-90011 40 mg + EC. The most common grade 3/4 AEs were neutropenia (63%) and thrombocytopenia (42%) with CC-90011 + EP, and thrombocytopenia (80%) and neutropenia (40%) with CC-90011 + EC. All 19 efficacy-evaluable pts achieved a partial response. PK profiles of the combinations were consistent with CC-90011 monotherapy. MMD expression decreased ≥50% at CC-90011 20 mg and 40 mg + EP and CC-90011 20 mg + EC in available samples.

Conclusions

CC-90011 + EP/EC is well tolerated in 1L ES SCLC with no new safety signals. The study is ongoing to further evaluate CC-90011 + EP/EC with nivolumab.

Clinical trial identification

NCT03850067; EudraCT: 2018-002799-42.

Editorial acknowledgement

This study was supported by Celgene, a Bristol Myers Squibb Company, with special thanks for the work performed by Li Li from Bristol Myers Squibb. Writing and editorial assistance were provided by Hannah Chang, PhD, of Bio Connections LLC, funded by Bristol Myers Squibb Company.

Legal entity responsible for the study

Celgene, a Bristol Myers Squibb Company.

Funding

Celgene, a Bristol Myers Squibb Company.

Disclosure

S. Ponce Aix: Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Takeda. O. Juan-Vidal: Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche/Genetech; Honoraria (self), Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: AbbVie; Honoraria (self): Takeda; Travel/Accommodation/Expenses: MSD. E. Carcereny: Advisory/Consultancy, Travel/Accommodation/Expenses: Takeda; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: MSD; Advisory/Consultancy: BMS. J.M. Trigo: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy: Bayer; Advisory/Consultancy: Boehringer; Advisory/Consultancy: Takeda; Advisory/Consultancy: GSK. L. Greillier: Research grant/Funding (institution): Celgene; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Sanofi; Advisory/Consultancy, Research grant/Funding (institution): Takeda; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Travel/Accommodation/Expenses: Boehringer. A. Navarro: Speaker Bureau/Expert testimony: Oryzon Genomics; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche. J. Bennouna: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self): Boehringer-Ingelheim; Honoraria (self): Servier; Honoraria (self): Bayer. A. Santoro: Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: AbbVie; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Celgene; Speaker Bureau/Expert testimony: Servier; Advisory/Consultancy, Speaker Bureau/Expert testimony: Gilead; Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Arqule; Speaker Bureau/Expert testimony: Lilly; Speaker Bureau/Expert testimony: Sandoz; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy: Sanofi. R. Berardi: Advisory/Consultancy: MSD; Advisory/Consultancy: Boehringer; Advisory/Consultancy: Ostura; Advisory/Consultancy: Lilly. B. Besse: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): BeiGene; Research grant/Funding (institution): Blueprint Medicines; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Cristal Therapeutics; Research grant/Funding (institution): Daiichi-Sankyo; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Ignyta; Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Inivata; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Merck KGaA; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Nektar; Research grant/Funding (institution): Onxeo; Research grant/Funding (institution): OSE immunotherapeutics; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Pharma Mar; Research grant/Funding (institution): Roche-Genentech; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Servier; Research grant/Funding (institution): Spectrum Pharmaceuticals; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Tiziana Pharma; Research grant/Funding (institution): Tolero Pharmaceuticals. J.L. Parra-Palau: Honoraria (self), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene/BMS. T. Sánchez-Pérez: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene - Bristol Myers Squibb Company. I. Aronchik: Shareholder/Stockholder/Stock options, Full/Part-time employment: BMS. E. Filvaroff: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: BMS; Shareholder/Stockholder/Stock options: Amgen; Shareholder/Stockholder/Stock options: Gilead; Shareholder/Stockholder/Stock options: Genentech/Roche.

M. Lamba: Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer; Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene (now part of Bristol Myers Squibb); Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol Myers Squibb. Z. Nikolova: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, A Bristol-Myers Squibb Company. L. Paz-Ares: Leadership role: ALTUM Sequencing; Leadership role: Genomica; Honoraria (self): Adacap; Honoraria (self): Amgen; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self): Bayer; Honoraria (self): Blueprint Medicines; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (self): Bristol-Myers Squibb; Honoraria (self): Celgene; Honoraria (self): Eli Lilly; Honoraria (self): Incyte; Honoraria (self): Ipsen; Honoraria (self): Merck; Honoraria (self), Research grant/Funding (self): Merck Sharp and Dohme; Honoraria (self): Novartis; Honoraria (self), Research grant/Funding (self): Pfizer; Honoraria (self): Pharmamar; Honoraria (self): Roche; Honoraria (self): Sanofi; Honoraria (self): Servier; Honoraria (self): Sysmex; Honoraria (self): Takeda. All other authors have declared no conflicts of interest.

Background

SCLC is characterised by high metastatic potential and dismal prognosis. LKB1 is a cell metabolism regulator and oncosuppressor. LKB1 downregulation has been associated with a cold TIME. LKB1 activates its main effector AMPK by phosphorylation. We aimed to analyse the role of LKB1 in SCLC in relationship to TIME and its association with prognosis.

Methods

We retrospectively evaluated all SCLCs consecutively treated at Istituto Oncologico Veneto and with available tissue from 1996 to 2015. LKB1, pAMPK, PD-L1 (22C3) on tumor cells (TC) and on tumor immune-infiltrating cells (TIIC), CD8 and FOXP3 were evaluated by immunohistochemistry (IHC). Semiquantitative scores were used to handle IHC results as categorical variables. Primary objectives were to assess the impact of LKB1 expression on overall survival (OS) and the association with TIME components.

Results

71 cases were included: 45 (63.4%) received surgery, 10 (14.1%) radical chemoradiotherapy, 16 (22.5%) chemotherapy. LKB1 IHC was positive in 63 (88.7%) SCLCs. LKB1 was highly positive (score > 3) in 55 (77.4%) cases. pAMPK was expressed in 38 (54.3%) out of 70 cases: 25/54 (46.3%) in LD SCLCs vs. 13/16 (81.3%) in extended SCLCs (p = 0.021). LKB1 score > 3 was associated with pAMPK expression (p = 0.047). LKB1 expression was significantly associated with a prolonged OS in the entire study population (median OS [mOS] 53.2 months [m], 95% CI: 20.8–72.4 vs. 21.9 m, 95% CI 1.6–not calculable [NC], p = 0.017; hazard ratio [HR] 0.40, 95% CI 0.18–0.87, p = 0.021) and in patients with LD-SCLCs (N = 55; mOS 65.7 m, 95% CI 44.5–107.1 vs. 27.4 m, 95% CI 16.3–NC, p = 0.013; HR 0.31, 95% CI 0.11–0.82, p = 0.019). No significant association was found between LKB1 and TIME; pAMPK was significantly associated with absent PD-L1 expression on TC (p = 0.040) and TIIC (p = 0.016).

Conclusions

LKB1/pAMPK deregulation may be associated with metastatic stage and lack of LKB1 expression warrants further validation as poor prognostic marker. Studies on a validation cohort of metastatic SCLC are ongoing while DNA genotyping of LKB1 is planned in LD.

Legal entity responsible for the study

Istituto Oncologico Veneto – IRCCS.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Small cell lung carcinoma (SCLC) is an extremely aggressive malignancy with poor prognosis. Recently, there have been improvements in identifying molecular subgroups and genetic pathways involved in the carcinogenesis of these tumors, but more effective therapies are needed.

Methods

We retrospectively identified patients with extended SCLC in which a Next Generation Sequencing (NGS) test was performed. Clinical characteristics and treatment outcomes were described. The statistical analysis was carried out with Stata15^®.

Results

1745 patients with lung carcinoma were analyzed. A tissue NGS was performed only in 15 out of 232 SCLC patients. Clinical characteristics of these were: median age 64 years, 53% male, 80% stage IV, 53,3% four or more metastatic localizations (liver (53,3%), CNS (40%)). ECOG 1, 69,2% and 0, 30,8% of patients. All patients received standard first-line chemotherapy. The median progression free survival (PFS) was 7 months, the median number of treatment lines was 2 and the median overall survival was 22 months. Molecular findings are described in the table. Most frequent alterations were mutations in RB1 and TP53. A third of patients (33%) had tumor mutational burden over 10 muts/Mb. One patient showed a pathogenic RET mutation but the PFS with a targeted treatment as third line was only 40 days.

Conclusions

Our cohort achieved longer survival than expected for advanced SCLC patients, although we only found one patient with a mutation suitable for targeted therapy. Further investigations are needed to understand the complexity of these tumors and the best therapeutic approaches for the different subgroups.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Small cell lung cancer (SCLC) accounts for 15% of total lung cancers and its 5-years overall survival is less than 10%. Recently, addition of anti-programmed death-ligand 1 (PD-L1) agents to chemotherapy has demonstrated marginally improved outcomes. The hepatocyte growth factor (HGF)/Met pathway activation is associated with chemo- and immune therapy resistance, and a worse prognosis in cancer. The aim of this study was to test the antitumoral effect of combining Met inhibition (savolitinib) with an anti-PD-L1 agent (durvalumab) in SCLC.

Methods

Expression of the targets of interest (Met and PD-L1) was determined by flow cytometry in the mouse KP1 SCLC cell line (Park K et al. Nature Medicine 2011). B16-F10 (Met exon 14 mutated) mouse melanoma cell line was used as positive control for expression. KP1 and B16-F10 cells were subcutaneously injected in B6129SF1/J and C57BL6/J mice, respectively. They were randomised into four groups (SCLC – n = 7; melanoma – n = 6 per group) and treated starting day-3 post-cell implantation with vehicle and isotype IgG (control group), savolitinib (30 mg/kg P.O. 5 days/week), durvalumab (10 mg/kg I.P. twice a week) or a combination of both compounds. Tumour growth was followed-up twice a week.

Results

KP1 cells showed low and no expression of Met and PD-L1, respectively, whereas B16-F10 cells showed high levels of both proteins in vitro. In in vivo models, tumour growth was significantly reduced (p < 0.05) by savolitinib plus durvalumab compared to the control after 18 days or 14 days of treatment in both KP1 (714.74 ± 124.35 mm³ vs. 418.17 ± 153.73 mm³) and B16-F10 (1295.31 ± 893.39 mm³ vs. 494.95 ± 156.08 mm³) syngeneic models, respectively. Moreover, we observed little effect of each drug alone in both Met mutant and wild-type models.

Conclusions

Our results show that combinatorial treatment with savolitinib plus durvalumab provides a significantly more effective antitumor effect than each agent alone and warrants further studies in SCLC. We hypothesize that this greater effect might be due to the modulation of certain functional immune cell subsets. Currently, immune infiltrates in both tumour models are being evaluated.

Legal entity responsible for the study

Fundació IMIM.

Funding

Instituto de Salud Carlos III (PI19/00003).

Disclosure

Á. Taus: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer-Ingelheim; Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Tesaro-GSK. E. Arriola: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda. All other authors have declared no conflicts of interest.

Background

Small-cell lung cancer (SCLC) accounts for 15% of pulmonary malignancies and is an aggressive disease with only little therapeutic progress in the last years. Aim of the current study is to characterize the utilization of platinum-etoposide (PE) chemotherapy in real-world SCLC management, as a basis for the predicting the potential penetration, and benchmark for assessing the clinical benefit of novel drugs in combination therapies.

Methods

Newly diagnosed patients in the years 2010–2017 were identified from the records of the Thoraxklinik Heidelberg and retrospectively analysed.

Results

Among 1189 primary patients, two-thirds (63%, n = 755) presented with extensive (ED), and 37% (n = 434) with limited disease (LD). For most ED-SCLC patients (66%, n = 496), first-line chemotherapy consisted exclusively of PE, 27% received other chemotherapies, mainly vincristine-etoposide, upfront or after switch in subsequent treatment cycles due to clinical deterioration, while 7% forewent systemic treatment altogether. The full course of 6 PE cycles was given to 47% of ED patients, with an average number of cycles per patient 4.6, a median duration of treatment 3.5 months, and a median progression-free survival of 5.8 months. In LD-SCLC, PE was used for 79% of patients exclusively, and for 16% along with other chemotherapeutics, while 5% of patients did not receive systemic treatment. Relapse or progression occurred in 80% of LD patients, in 27% already within the same year of initial diagnosis. Median overall survival (mOS) was 9.9 months for PE-treated ED and 20.4 months for PE-treated LD-SCLC patients, with a 5-year OS rate of 1% and 21%, respectively.

Conclusions

PE is the first-line systemic treatment for approximately two-thirds of ED and 80% of LD SCLC patients, but has limited activity, with mOS below 1 year and long-term benefit in only about 20% of cases, respectively. Besides highlighting the need for novel therapeutic strategies, these results define the size of the target population and the efficacy threshold for promising add-on drugs in the routine setting.

Legal entity responsible for the study

Thoraxklinik Heidelberg gGmbH.

Funding

Has not received any funding.

Disclosure

F. Bozorgmehr: Honoraria (self), Research grant/Funding (self): BMS; Honoraria (self): MSD. R. Elshafie: Honoraria (self), Research grant/Funding (self): Accuray; Honoraria (self): AstraZeneca; Honoraria (self): BMS; Honoraria (self): Novocure; Honoraria (self): Merck; Honoraria (self): Takeda. J. Kuon: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Research grant/Funding (self): Celgene. C-P. Heussel: Honoraria (self): Novartis; Honoraria (self): Basilea; Honoraria (self): AstraZeneca; Shareholder/Stockholder/Stock options: GSK. F. Herth: Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Roche; Honoraria (self), Research grant/Funding (self): Novartis. A. Stenzinger: Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): BMS; Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self), Research grant/Funding (self): Thermo Fisher; Research grant/Funding (self): Chugai; Research grant/Funding (self): Illumina. M. Thomas: Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Roche; Honoraria (self), Research grant/Funding (self): Takeda; Honoraria (self), Research grant/Funding (self): Novartis. P. Christopoulos: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self), Research grant/Funding (self): Takeda; Honoraria (self): Pfizer; Honoraria (self): Boehringer; Honoraria (self), Research grant/Funding (self): Novartis. All other authors have declared no conflicts of interest.

Background

Comorbidity is increasingly common in SCLC and may significantly affect treatment tolerability and patient outcome. Cardiopulmonary comorbidity thus needs to be carefully considered when making treatment choices. However, cardiopulmonary stress can be challenging to evaluate clinically in these patients, which warrants biomarkers as a tool for objective assessment and individualised treatment decision. Here, we have investigated circulating levels of the vasoactive peptides adrenomedullin (ADM), atrial natriuretic peptide (ANP) and arginine vasopressin (AVP), known to correlate with various aspects of cardiopulmonary pathology, in a large cohort of SCLC patients within a randomised controlled trial (RASTEN; Ek L. et al, Ann Oncol 2018).

Methods

Plasma concentrations of stable fragments of the peptide precursors midregional pro-ADM (MR-proADM), midregional pro-ANP (MR-proANP) and C-terminal pre-provasopressin (copeptin, surrogate marker of AVP) were measured in EDTA-plasma collected at baseline, using a standardised, commercial immunoluminometric sandwich assay (KRYPTOR, Thermo Fisher Scientific, Germany).

Results

A total of 252 RASTEN trial patients were included in the present cohort, of which 104 (41%) had limited disease (LD) and 148 (59%) had extensive disease (ED). For all three biomarkers, increasing levels were associated with reduced survival, particularly in patients with ED. The associations were strongest with MR-proADM, where the top versus bottom quartile was associated with an adjusted hazard ratio (HR) for overall survival of 2.13 (95% CI 1.34–3.40; P = 0.001) in the entire cohort, and 4.08 (95% CI 2.12–7.84; P = <0.001) in patients with ED. This corresponded to a median overall survival (OS) of 6.7 months and 17.1 months, in patients with the highest and lowest MR-proADM levels, respectively.

Conclusions

In this large clinical trial cohort, we have shown that in particular MR-proADM may be a useful cardiovascular biomarker that strongly correlates to survival in SCLC. Further prospective studies are warranted to validate the clinical utility of MR-proADM for improved, individualised treatment decisions in SCLC and potentially other malignancies.

Legal entity responsible for the study

Lund University, Sweden.

Funding

Governmental funding of clinical research within the national health services, ALF Swedish Research Council Swedish Cancer Society.

Disclosure

All authors have declared no conflicts of interest.

Background

Small cell lung cancer (SCLC) generally occurs in men, mainly related to smoking. However, the main risk factors of female non-smoking patients with small cell cancer are unknown. This study aims to explore the clinical characteristics of female SCLC and the influence of two major risk factors: smoking and long-term second-hand smoke inhalation on the disease.

Methods

Female patients with SCLC diagnosed in Shanghai Chest Hospital from 2014 to 2018 were enrolled. The information of smoking history, long-term second-hand smoking history and other characteristics were evaluated. In order to reduce the bias and to scientifically evaluate the impact of smoking status and long time second-hand smoking status on female SCLC, we used the Propensity score matching (PSM) analysis method to compare them in a 1:1 ratio in this non randomized study. Comprehensive genomic profiling was performed on DNA extracted from 35 samples by next generation sequencing (NGS) with a panel of 68 cancer-related genes.

Results

323 patients were finally enrolled, including only 21(6.5%) smokers but 206(63.8%) cases with long-time second-hand smoke inhalation history. After PSM, smoking status made no statistical difference on PFS(p = 0.163) and OS(p = 0.983). However, patients with long-time second-hand smoking history had worse PFS (No vs. Yes,11.1 m vs. 8.7 m, HR = 1.451, 95%CI: 1.093–1.927, p = 0.009) and OS(No vs. Yes,18.9 m vs. 15.8 m, HR = 1.460, 95%CI: 1.088–1.960, p = 0.011). Multivariate analysis of clinical characteristics showed that long time second-hand smoking history(p = 0.004), cTNM stage(p < 0.001), surgery(p = 0.018), chemotherapy(p < 0.001) and PCI(p < 0.001) were independent prognostic factors of OS. EGFR mutation was identified in 7 never-smoke cases, 3 SCLC combined with adenocarcinoma.

Conclusions

Although most female patients with SCLC had no history of smoking, the proportion of them with long-term history of second-hand smoke inhalation was very high. And patients with second-hand smoking history were tend to have worse prognosis. A relatively higher frequency of EGFR mutations were observed in female patients, though it is still unclear how effective EGFR-TKIs are for EGFR-mutated SCLCs.

Legal entity responsible for the study

Lei Yuqiong.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Definitive chemoradiotherapy is still the standard treatment for limited stage small cell lung cancer (LS-SCLC). Previous studies suggested the prognostic value of the Lung Immune Prediction Index (LIPI) and the Gustave Roussy Score (GRIM) as prognostic markers in advanced small cell lung cancer (SCLC). However, LIPI and GRIM score have not been evaluated in patients with LS-SCLC.

Methods

Pretreatment LIPI and GRIM score of 33 (43%) patients out of 77 LS-SCLC patients treated with chemoradiotherapy (CRT) during 2004–2015 were included. The LIPI score was based on dNLR greater than 3 and LDH greater than upper limit of normal (ULN) and characterizes 3 groups (good, 0 factors; intermediate, 1 factor; poor, 2 factors). The GRIM score is calculated by neutrophil-to-lymphocyte ratio (>6), lactate dehydrogenase (LDH) greater than upper ULN, and serum albumin concentration (<3,5). Both scores were calculated before start of chemoradiotherapy and follow-up was conducted until death or at least 2 years.

Results

The median overall survival (OS) time in the good, intermediate, and poor LIPI subgroups were 14, 17 and 3 months (p = 0.973) and 14, 17 and 17months in the GRIM subgroups (p = 0.984). In univariate analysis, patients age <65years (p = 0.008), concurrent chemotherapy (p = 0.028), and administering prophylactic cranial irradiation (PCI) (p = 0.031) were associated with improved OS. Using Cox regression analysis, age remained significant (HR = 3.299, p = 0.031) and PCI showed a trend (HR = 2.801, p = 0.06).

Conclusions

Independent predictors of overall survival were identified and can contribute to improved treatment personalization. Concurrent chemotherapy and PCI after CRT were associated with improved OS compared to LIPI- and GRIM score, which had no prognostic impact in LS-SCLC.

Legal entity responsible for the study

The authors.

Funding

LMU university hospital.

Disclosure

All authors have declared no conflicts of interest.

Background

Recurrent small cell lung cancer (SCLC) is associated with a dismal prognosis and treatment options are still limited. In this study, we evaluated the outcome of thoracic reirradiation for locally recurrent small cell lung cancer in order to identify prognostic factors and assess treatment-related toxicity.

Methods

Data of 33 patients with a loco-regional recurrence of SCLC, who underwent reirradiation at 4 international university hospitals between 2008 and 2015, were analyzed. Initial treatment consisted of concurrent platinum-based chemoradiotherapy in 91% of all patients. Prophylactic cranial irradiation after definitive chemoradiotherapy was applied in 76% of the patients. Reirradiation doses ranged from 20 to 87.50 Gy (median: 32.50 Gy). At the time of the second radiation course, concurrent chemotherapy was given in 3 patients (9%) using topotecan. Overall survival (OS), acute and late toxicities of thoracic reirradiation were evaluated and prognostic factors were identified.

Results

Reirradiation was performed at a median interval time of 24 months after the first thoracic radiation course. Median survival after reirradiation was 7 months (range, 1–54 months). The 1- and 2-year OS were 33% and 17%, respectively. Patients with a good performance status (KPS >70%, p = 0.016), absence of extrathoracic disease (p = 0.001), reirradiation dose (EQD2) of >40 Gy (p = 0.019) and a cumulative dose of first plus second series of radiotherapy (EQD2) >90 Gy (p = 0.019) were associated with improved OS. Acute pulmonary Grade 1–2 toxicity from re-irradiation was recorded in 11 patients (33%) and grade 3 acute toxicity was encountered in 1 patient (3%).

Conclusions

Reirradiation for locally recurrent SCLC is safe and shows promising outcomes. Patients reirradiated with doses >40 Gy experienced more favorable survival rates. In contrast, patients with a poor performance status or extrathoracic disease have a poor prognosis and should be considered only for symptom control in this group.

Legal entity responsible for the study

The authors.

Funding

LMU University Hospital.

Disclosure

All authors have declared no conflicts of interest.