Background

Circulating tumor DNA (ctDNA) based liquid biopsies (LB) have significantly advanced clinical care for NSCLC patients by improving access to molecular testing. A key benefit of certain LB approaches is fast turnaround time (TAT), which can accelerate treatment initiation. We prospectively evaluated the feasibility, accuracy, and TAT of OncoBEAM EGFR, KRAS and BRAF genotyping in a cohort of NSCLC patients seen at a single institution in routine clinical practice. Alterations in these genes directly inform the use of approved (EGFR, BRAF) and emerging (KRAS G12C) targeted therapies, and due to mutual exclusivity with gene fusions in ALK/ROS/RET, may obviate the need for additional molecular testing.

Methods

Whole blood samples (n = 187) were collected from metastatic NSCLC patients and sent to a CLIA lab for OncoBEAM digital PCR analysis of EGFR (exon 19 del, L858R, T790M, C797S), KRAS (codons 12, 13, 61), and BRAF V600E. Forty samples were analyzed prospectively to assess TAT and 147 samples were analyzed retrospectively. Samples with sufficient residual plasma (n = 176) were tested with SafeSEQ, an orthogonal NGS-based LB assay. TAT was calculated as number of days from specimen receipt to results.

Results

The mean TAT of OncoBEAM results for 40 samples prospectively tested was 4.25 ± 0.98 days (95% CI: 3.94–4.56), with the most and least rapid results delivered within 3 and 6 days, respectively. For the same 40 patients, the mean TAT of tissue-based genotyping was 12.13 ± 4.42 days (95% CI: 10.68–13.59). Of 54 (29%) ctDNA positive patients in the full cohort (n = 187), EGFR, KRAS, and BRAF mutations were detected in 30 (56%), 25 (46%), and 0 samples, respectively. The median mutant allele frequency (MAF) for all mutations detected by OncoBEAM was 0.50% (range: 0.04–50.84%), where 64% and 23% of mutations were detected with MAF <1% and <0.1%, respectively. Concordance of results between OncoBEAM and SafeSEQ in 176 replicate samples revealed an overall percent agreement of 99.6% with strong linear correlation of MAF (R² = 0.98).

Conclusions

OncoBEAM LB enables sensitive and accurate genotyping results within 5 days, ∼3x faster than the TAT of tissue genotyping results, which carries significant implications for enabling rapid implementation of targeted therapies for NSCLC patients.

Legal entity responsible for the study

The authors.

Funding

Sysmex Inostics.

Disclosure

H. Sloane: Full/Part-time employment: Sysmex Inostics, Inc. D. Edelstein: Full/Part-time employment: Sysmex Inostics, Inc. F. Jones: Full/Part-time employment: Sysmex Inostics, Inc. J. Preston: Full/Part-time employment: Sysmex Inostics, Inc. F. Holtrup: Full/Part-time employment: Sysmex Inostics, Inc. H. Quinn: Full/Part-time employment: Sysmex Inostics, Inc. All other authors have declared no conflicts of interest.

Background

Immune Checkpoint Inhibitors (ICI) have become a care standard in advanced non-small cell lung cancer (aNSCLC). Myeloid-Derived Suppressor Cells (MDSC) are potent immunity suppressors and may represent both a potential prognostic and a predictive biomarker. Neutrophil-to-Lymphocyte Ratio (NLR) is an inflammatory biomarker with a prognostic role in NSCLC. We hypothesized that MDSC levels correlate with NLR and overall survival (OS) in aNSCLC.

Methods

Pretreatment immunophenotyping of total MDSC (HLA-DR−/CD33+/CD11b+), early-MDSC (e-MDSC: CD14−/CD15−), monocytic-MDSC (M-MDSC: CD14+/CD15−) and polymorphonuclear-MDSC (PMN-MDSC: CD14−/CD15+) was performed by flow cytometry in fresh blood. Spearman's rank correlation, univariate and multivariate Cox proportional hazard models were used for data analysis (SPSS Statistics v20).

Results

100 patients treated with ICI who received at least one previous platinum-based combination chemotherapy for stage III–IV NSCLC and 14 healthy donors were prospectively included; 93% smokers, median age 63 years (range 38–80); 60% non-squamous and 50% PDL1 ≥1%. Median PFS (mPFS) and mOS was 2.98 m (95% CI, 0.92–4.85) and 11.83 m (95% CI, 9.46–13.85). Pretreatment high-NLR, dichotomized at a ROC curve analyses cutoff value ≥5.17, and high level of total MDSC, defined by the median value as a cut-off (≥6.3%), were correlated with poor PFS (NLR: p = 0.042 and MDSC: p = 0.038) and OS (NLR: p < 0.0001 and MDSC: p = 0.004). Pretreatment low e-MDSC (<21.1%), were also associated with poor PFS (p = 0.02) and OS (p = 0.03). Both total MDSC (Spearman's rho = 0,40; p < 0.0001) and PMN-MDSC (Spearman's rho = 0.29; p < 0.0001) were positively correlated with NLR. Multivariate analyses confirmed that higher NLR and higher total MDSC levels were independently associated with shorter OS (NLR HR 3.45; p = 0.005 and total MDSC HR 3.24; p = 0.021).

Conclusions

Our study suggests that a baseline circulating MDSC correlate with NLR. Higher total MDSC levels and higher NLR were negative prognostic factors. The role of MDSC appears interesting as a potential predictive and prognostic biomarker in NSCLC patients treated with ICI.

Legal entity responsible for the study

Instituto de Investigación Sanitaria - Fundación para la Investigación del Hospital Universitario la Fe.

Funding

Roche Farma, S.A.

Disclosure

All authors have declared no conflicts of interest.

Background

Anlotinib, an oral multi-target TKI antiangiogenic Inhibitor, has been recommended by guidelines for the 3rd line or more treatment of NSCLC in China, but its effectiveness in combination in first-line treatment remains unknown. Therefore, this study aimed to evaluate efficacy and safety of anlotinib in combination with erlotinib, chemotherapy or sintilimab, respectively.

Methods

In this open-label, threearm, prospective study, advanced NSCLC patients with EGFR mutation (Cohort A) receive anlotinib and erlotinib; for patients with EGFR mutation negative, the treatment regimen was anlotinib in combination with chemotherapy (Cohort B) or sintilimab (Cohort C) according to investigator. All patients received treatment until disease progression or treatment intolerance. The primary outcome was ORR, the secondary outcomes were PFS, DCR, OS and safety.

Results

A total of 80 patients were enrolled, in Cohort A 30 patients, Cohort B 28 patients and Cohort C 22 patients. The final follow-up deadline was 20 Dec 2020, In Cohort A, 26 patients achieved confirmed PR, ORR was 92.9%, and DCR was 96.4%. Median PFS was 20.5 months, and 12-month PFS rate was 81.5%. In Cohort B, ORR was 60.0%, while DCR was 96.7%. Median PFS was 13.3 months, and 12-month PFS rate was 55.5%. In Cohort C, medium PFS was 15.6 months. The 18- and 24-month PFS rate was 45.9% and 26.2%, respectively. The median OS of the three arms has not been reached. The most common grade 3 adverse events (AEs) were rash (17.2%), oral mucositis (10.3%), diarrhea (6.9%) and proteinuria (6.9%) in Cohort A, and a grade 4 hypertension was observed. In Cohort B, the most common grade 3 AEs were platelet count decreased (20.0%), leucopenia (16.7%), hand-foot-skin reaction (10.0%), hypertriglyceridemia (10.0%), oral mucositis (6.7%) and thrombus (6.7%). Safety data of Cohort C has been published elsewhere.

Conclusions

This study suggests that anlotinib-based combination therapy for patients with advanced NSCLC might be a new first-line therapy strategy. For EGFR-mutated positive patients, anlotinib plus erlotinib shows good efficacy and tolerability. For EGFR-mutated negative patients, anlotinib combines with chemotherapy or sintilimab also may be a promising first-line treatment.

Clinical trial identification

NCT03628521.

Legal entity responsible for the study

Baohui Han.

Funding

Shanghai Jiao Tong University.

Disclosure

All authors have declared no conflicts of interest.

Background

Chemotherapy-induced neutropenia (CIN) has a prognostic role in several cancer conditions. We previously demonstrated a significant prognostic value of CIN on overall survival (OS) in a pooled dataset of pts with aNSCLC receiving first line chemotherapy (CT) from 1996 to 2001. However, the prognostic role of CIN in NSCLC is still debated.

Methods

We performed a post hoc analysis pooling data prospectively collected in six randomized phase III trials in aNSCLC conducted from 2002 to 2016: CALC1 (NCT00330746), GECO (NCT00385606), TORCH (NCT00349219), MILES2 (NCT00401492), MILES3 (NCT01405586) and MILES4 (NCT01656551). All trials tested first-line treatment and primary results have already been published. Pts assigned to CT arms or combination arms of CT with other non-cytotoxic drugs (rofecoxib in GECO and cetuximab in CALC1), that had received at least one cycle of CT and for whom at least one toxicity case report form was available, were considered eligible for the analysis. Neutropenia was categorized on the basis of worst NCI-CTC/CTCAE grade during CT: absent (G0), mild (G1–2), or severe (G3–4). The primary endpoint was OS. Multivariable Cox model was applied for statistical analyses. A landmark at 180 days from randomization was applied to minimize the time-dependent bias.

Results

Overall, 1529 out of 1963 pts enrolled in the trials were considered eligible. 572 of them (who received 6 cycles of treatment) represented the landmark population. Severe CIN was reported in 143 (25.0%) pts and mild CIN in 135 (23.6%). At multivariable OS analysis, CIN was significantly predictive of prognosis although its prognostic value was entirely driven by severe CIN (HR of death 0.71; 95%CI: 0.53–0.95) while it was not evident with mild CIN (HR 1.21; 95%CI: 0.92–1.58). Consistent results were observed in the out-of-landmark group (including 957 pts), where both severe and mild CIN were significantly associated with a reduced risk of death.

Conclusions

This pooled analysis of six large trials of aNSCLC treatment shows a significant improvement of OS in pts developing CIN, particularly in those developing severe CIN, confirming our previous findings.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C. Gridelli: Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Amgen; Advisory/Consultancy: Menarini. A. Morabito: Advisory/Consultancy: Pfizer; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Takeda; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Boehringer; Advisory/Consultancy: Eli-Lilly; Advisory/Consultancy: Roche. F. Ciardiello: Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Servier; Advisory/Consultancy: BMS; Advisory/Consultancy: Celgene; Advisory/Consultancy: Lilly; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Ipsen; Advisory/Consultancy, Research grant/Funding (institution): Roche. V. Gebbia: Speaker Bureau/Expert testimony: Eli-Lilly. C.M. Della Corte: Advisory/Consultancy: MSD. F. Morgillo: Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: MSD; Advisory/Consultancy: Lilly. A. Gravina: Travel/Accommodation/Expenses: Pfizer. M. Di Maio: Research grant/Funding (institution): Tesaro-GlaxoSmithKline; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Janssen; Advisory/Consultancy: Astellas; Advisory/Consultancy: Takeda; Advisory/Consultancy: Eisai; Advisory/Consultancy: Merck Sharp & Dohme. F. Perrone: Advisory/Consultancy: Bayer; Advisory/Consultancy: Ipsen; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: Sandoz; Advisory/Consultancy: Incyte; Advisory/Consultancy: Celgene; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Janssen-Cilag. M.C. Piccirillo: Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: GSK; Advisory/Consultancy: MSD; Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Travel/Accommodation/Expenses: Bayer. All other authors have declared no conflicts of interest.

Background

There is limited data on prognostic value of baseline plasma cfDNA in advanced squamous NSCLC. The current study aimed to assess change in plasma cfDNA levels in locally advanced/metastatic Sq-NSCLC with chemotherapy & its correlation with symptom scores & radiological responses.

Methods

Prospective observational study involving chemotherapy-naïve stages IIIB/IIIC/IV (8^th TNM) Sq-NSCLC patients at a tertiary referral centre. Being a pilot study, enrolment was planned for 50 Sq-NSCLC patients, 25 smokers with COPD (COPD-controls; CC) & 25 healthy controls (HC). Respiratory Symptom Burden (RSB) was calculated from mean Visual Analog Scores (VAS) of dyspnoea, cough, chest pain & hemoptysis. Total Symptom Burden (TSB) was calculated from mean VAS scores of above 4 symptoms + anorexia & fatigue. cfDNA was isolated >2 hours of obtaining 5 ml of peripheral blood using MagMAX^TM Cell-Free DNA Isolation Kit. It was analyzed & quantitated using Agilent^TM High Sensitivity DNA Kit & Agilent^TM Bioanalyzer 2100. All patients received standard platinum-doublet chemotherapy. RSB/TSB/cfDNA assessment & CECT scans of thorax were all done at baseline & after 4 chemotherapy cycles.

Results

Final enrolment was 59 Sq-NSCLC, 27 CC & 25 HC. At baseline, 13/59 (22%) Sq-NSCLC, 3/27 (11%) CC & none (0%) HC had detectable cfDNA. All 3 CC were heavy smokers with no evidence of malignancy & undetectable cfDNA levels on repeat testing. In Sq-NSCLC group, majority were males (95%), current smokers (88%), heavy smokers (70%), had metastatic disease (59%) with median age of 65 years. ECOG PS was 0–1 (56%) and 2 (42%). Median RSB & TSB scores were 9 (IQR = 5–14) & 16 (IQR = 9–23) respectively. 54/59 patients received ≥1 cycle & 27 underwent post-C4 evaluation with detectable cfDNA levels in 18/27 (6.7%). No baseline characteristic correlated with cfDNA detectability. Median OS & PFS were 262 days & 167 days respectively. ECOG PS>2, RSB score >9 & TSB score >16 were all associated with worse OS & PFS as was cfDNA detectability [Median OS = 97 vs. 271 days; p = 0.045; HR = 2.32Median PFS = 93 vs. 182 days; p = 0.027; HR = 2.28].

Conclusions

Baseline cfDNA detectability is independently associated with poor OS and PFS in advanced Sq-NSCLC patients on chemotherapy.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Rapidly evolving treatment options for advanced NSCLC can lead to difficulties in implementing those changes in daily practice. Insight into real-world treatment choices might help identify needs for better patient care.

Methods

215 consecutive metastatic treatment-naïve NSCLC patients were prospectively enrolled in BEPACT Lung (NCT03959137) between June-Oct 2019 in 21 Belgian hospitals. Data collected: treatment site (high vs low volume (HV vs LV)); patients’ characteristics (demographics, medical history, comorbidities, autoimmune disease, medications, prior treatment for earlier stage NSCLC); tumor characteristics; patients’ preference; treatment type (chemotherapy (C), immunotherapy (I), immuno-chemotherapy (I+C), best supportive care (BSC)). The primary objective was to identify factors influencing the treatment choice using first a simple logistic regression model, and then entering factors with p < 0.25 in a multiple logistic regression model.

Results

HV and LV centers showed similar patients’ characteristics. Median age 68.2 years, 65.1% male, 77% performance status (PS) ≤1, 95.7% (former)smokers, 65.6% non-squamous, 42.1% Programmed Death-Ligand1 (PD-L1) high (≥50%). In the PD-L1 high group, simple logistic regression pointed at age (p = .0167), prior treatment (p = .0544), tumor size (p = .0643), number of comorbidities (p = 0.1679) and weight loss (p = .2146) as factors in the choice of I alone vs I+C; in the multiple regression model, this was age (p = .0642), weight loss (p = .0458) and prior treatment (p = .0582). In the PD-L1 low group, simple logistic regression pointed at PS (p < 0.0001), weight loss (p = .0440), patients’ preference (p = .0636), age (p = .1149), antibiotics (p = .1366) and smoking status (p = 0.1566) for the choice of I+C vs C alone or BSC; in multivariate analysis, this was PS (p = .0005), age (p = .0308), and patients’ preference (p = .0585).

Conclusions

In PD-L1 high tumors, the choice of I alone (vs I+C) was more likely with higher age, more weight loss, and no prior treatment. In PD-L1 low tumors, the choice of I+C (vs C alone/BSC) was more likely in case of good PS, younger age or patients’ preference.

Clinical trial identification

NCT03959137 Study Start date: June 1, 2019 Study Completion date: October 31, 2019.

Legal entity responsible for the study

Merck Sharpe & Dohme Corp.

Funding

Merck Sharpe & Dohme.

Disclosure

A. Sibille: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Takeda. K. Cuppens: Advisory/Consultancy: Merck Sharpe & Dohme; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: Roche. S.H. Coulon: Full/Part-time employment: Merck Sharpe & Dohme. L. Decoster: Honoraria (institution): Lilly; Advisory/Consultancy: Roche; Research grant/Funding (self): Boehringer Ingelheim; Travel/Accommodation/Expenses: Merck Sharp & Dohme; Travel/Accommodation/Expenses: Roche. I. Demedts: Advisory/Consultancy: Merck Sharpe & Dohme; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Takeda; Advisory/Consultancy: Lilly; Advisory/Consultancy: Glaxo Smith Kline. K. Deschepper: Advisory/Consultancy: Merck Sharpe & Dohme; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Lilly; Research grant/Funding (institution): Merck Sharpe & Dohme; Research grant/Funding (institution): Chiesi. A. Janssens: Advisory/Consultancy: AstraZeneca. S. Ocak: Advisory/Consultancy: Merck Sharpe & Dohme; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Takeda. V. Pruniau: Full/Part-time employment: Merck Sharpe & Dohme. J.F. Vansteenkiste: Advisory/Consultancy: Merck Sharpe & Dohme; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sanofi; Research grant/Funding (institution): Merck Sharpe & Dohme. All other authors have declared no conflicts of interest.

Background

Cancer-related fatigue (CRF) among patients with lung cancer (LC) is present before and after treatment and present in about three fourth of cases. CRF is often a common unmet need affecting the quality of life of patients with LC. We conducted this study to understand the predictors for CRF among patients with LC attending the palliative care department in our center.

Methods

A prospective observational study was conducted among patients having LC. The study was conducted on patients referred to the palliative care department of Tata Medical Center, Kolkata from January 2019 to June 2019. Those patients whose Karnofsky status is less than 40, with a history of diabetes, heart disease, psychiatric disease, and psychotropic drugs were excluded from the study. Edmonton Symptom Scale was used to assess the various symptoms like pain, fatigue, nausea, depression, anxiety, appetite, well-being, cough, and shortness of breath. History of any surgery, chemotherapy, or radiotherapy along with blood investigations like serum albumin, hemoglobin, and white blood cell count was documented.

Results

Eighty-four patients with LC with a mean age of 61.5 years were included in the present study. The prevalence of CRF was 48.80%. Univariate analysis revealed that the presence of cough (p < 0.001), breathlessness (p < 0.001), hemoglobin levels (p = 0.012), and radiotherapy treatment (p = 0.038) to be associated with fatigue. After multiple logistic regression analysis with fatigue as outcome variable, revealed that presence of cough [OR = 3.80; 95% CI = 1.13 to 12.80;(p = 0.031)] and breathlessness [OR = 3.57; 95% CI = 1.19 to 10.73; (p = 0.023)] as significant predictors affecting fatigue among lung cancer patients.

Conclusions

Half of our patients with LC had CRF. The presence of cough and breathlessness were significant factors that affected the CRF in the present study after the confounding factors were adjusted. Further studies on this associated symptom cluster of fatigue, breathlessness, and cough have to be conducted. While managing the patients with fatigue it is important that these associated symptoms like cough and breathlessness have to be handled.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Because of the poor prognosis of lung cancer, it is important to take into account the quantity and quality of survival in treatment decision-making. It is therefore important to consider the impact of toxicity on health-related quality of life (HRQoL). We report the results on the association between patient-reported HRQoL and toxicity in stage locally advanced (LA-) and metastatic non-small cell lung cancer (NSCLC) patients receiving systemic therapy and/or radiotherapy in the PRO-Long study.

Methods

PRO-Long is a prospective, longitudinal study on the effect of systemic therapy and/or radiotherapy on HRQoL, toxicity, functional exercise capacity and neuro-cognitive functioning in LA- and metastatic NSCLC patients. HRQoL and toxicity data was collected pre-therapy and repeatedly until 1 year after therapy, respectively with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). HRQoL scores were calculated based on EORTC guidelines. Overall toxicity scores were translated into the Standardized Total Average Toxicity (STAT) score. Individual toxicity scores were calculated by subtracting baseline scores from subsequent data point scores. Multi-level analyses were applied to assess statistical significance (<0.01).

Results

In total, 50 patients were recruited. The majority had stage III disease (54%), was male (60%) and received chemotherapy with (50%) or without (24%) radiotherapy. Toxicity is associated with overall HRQoL (p = 0.000) and physical (p = 0.000), cognitive (p = 0.000), role (p = 0.000) and emotional (p = 0.000) functioning. HRQoL is associated with loss of appetite (p = 0.000), fatigue (p = 0.000), dyspnea (p = 0.001), cough (p = 0.000), diarrhea (p = 0.000), constipation (p = 0.008), anxiety (p = 0.007) and depression (p = 0.000). Fatigue, cough and depression significantly impact the majority of HRQoL domains.

Conclusions

Toxicity may impact overall and certain HRQoL domains in LA- and metastatic NSCLC patients receiving systemic or combined therapy. It is therefore important to consider the impact of toxicity on HRQoL in this vulnerable patient population.

Legal entity responsible for the study

The authors.

Funding

Funding Agency for Innovation by Science and Technology (IWT), Brussels, Belgium. Contract number: IWT TBM 130262.

Disclosure

All authors have declared no conflicts of interest.

Background

Non-small cell lung cancer (NSCLC) is the most frequent type of lung cancer that is associated with highest morbidity and mortality rate. Anlotinib is an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase that is used as third-line treatment for NSCLC. The objective of this study was to evaluate the overall survival in patients with advanced NSCLC treated with anlotinib.

Methods

Data was collected until January 5^th 2021 from PMC, PubMed, Google Scholar, Science Direct, and Scopus, using combination of keywords associated with advanced NSCLC and treatment using anlotinib in relation to their overall survival. Publications included are limited to English manuscripts that were published in the past 10 years. The studies include patients with advanced NSCLC and exclude patients with brain metastases that were controlled or uncontrolled for less than two months. All studies were reviewed and evaluated by authors. The quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS), with four studies were in moderate quality and one study was in good quality. Studies were also assessed using GRADE and showed moderate quality of evidence as there are neither inconsistency nor publication bias.

Results

A total of five studies consisting of four clinical trial studies and one cohort study with a total of 1,353 advanced NSCLC patients were included. Studies claimed that anlotinib showed better PFS (HR = 0.48; 95% CI: 0,23–1.00; P = 0.05) and significantly improved OS (HR = 0.75; 95% CI: 0.67–0.83; P < 0.00001) compared to the placebo group. One study also presented better PFS and OS in refractory advanced NSCLC patients treated with anlotinib compared to the placebo group.

Conclusions

Anlotinib is proven to be beneficial compared to placebo in treating advanced NSCLC patients as it shows significant improvement in overall survival and also better progression free survival. Studies also found that anlotinib possess remarkable efficacy and manageable safety profile, therefore should always be considered as candidate for treatment in advanced NSCLC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Qualitative research was conducted with adults with EGFR-mutated NSCLC to debrief two patient-reported outcomes (PROs), the PROMIS-PF-8c and NSCLC-SAQ, confirm their content validity, and ensure they are clear, relevant, and appropriate for use with this population.

Methods

Concept elicitation (CE) and combined CE/cognitive debriefing (CD) interviews were conducted with adults with locally advanced or metastatic EGFR-mutated NSCLC identified from lung cancer patient advocacy groups and online sources. The CE portion of the interview sought to understand important concepts of NSCLC. Subjects then completed the PROMIS-PF-8c and NSCLC-SAQ, and answered questions to evaluate their content, clarity, and relevance. The study received IRB approval; subjects provided written informed consent.

Results

30 patients were interviewed [87% female, 80% Caucasian, mean age 57 ± 12 years, 63% from US, 70% with Exon20 insertion mutation]. The most common NSCLC symptoms and impacts are reported below.

The most bothersome symptoms were shortness of breath (43%), pain other than chest pain (29%), cough (29%), and fatigue (21%). Fatigue was the most difficult symptom to manage (38%). In general, patients were able to accurately paraphrase each item and found them to be clear, relevant, and meaningful. All symptoms and impacts were mapped to the content of these two PROs and were endorsed by > 20% of patients. One of the most common impacts, difficulty with physical functioning, was covered in the PROMIS-PF-8c, while the NSCLC-SAQ contains all the most frequently reported NSCLC symptoms.

Conclusions

Content validity of the PROMIS-PF-8c and NSCLC-SAQ has been confirmed in patients with EGFR-mutated NSCLC. Measurement properties will be evaluated using data from upcoming clinical studies.

Legal entity responsible for the study

Janssen Global Services, LLC.

Funding

Janssen Global Services, LLC.

Disclosure

K. Liu: Full/Part-time employment: Janssen Pharmaceuticals. S.D. Mathias: Full/Part-time employment: Health Outcomes Solutions. H.H. Colwell: Full/Part-time employment: Health Outcomes Solutions. T. Li: Full/Part-time employment: Janssen Pharmaceuticals. P. Mahadevia: Full/Part-time employment: Janssen Pharmaceuticals. R.F. Pierson: Full/Part-time employment: Janssen Pharmaceuticals. All other authors have declared no conflicts of interest.

Background

Docetaxel is the standard second-line chemotherapy drug for advanced NSCLC, but the treatment effect is still limited. Antiangiogenic drugs can also potentially support vessel normalization to help deliver chemotherapy drugs for better clinical benefit, in addition to having anti-angiogenic and anti-tumor effects. Anlotinib, as one of the new antiangiogenic drugs, significantly improved both PFS and OS of advanced NSCLC patients and were approved by NMPA as third-line treatment in a phase III trial (ALTER0303). So here, we present recent data from a cohort of patients who received anlotinib plus docetaxel after first-line chemotherapy in the prospective phase II clinical trial ALTER-L024 (NCT03732001).

Methods

Advanced NSCLC patients progressed after first-line chemotherapy were assigned to treat with docetaxel at a dose of 60 mg per square meter of body-surface area and anlotinib at a dose of 12 mg oral per day for 2 weeks every 3 weeks in the treatment group. Progression free survival (PFS) was primary endpoint, and objective response rate (ORR), disease control rate (DCR) and safety were secondary endpoints.

Results

At data cut-off (November 4, 2020), we recruited 22 patients (pts) in the combination cohort of this phase II trial. Most pts were male (81.8%), former/current smokers (81.8%) and non-squamous cell histology (68.2%). Among 17 pts who had received at least one tumor assessment, four pts achieved PR, twelve pts achieved SD and only one patient developed to disease progression. The ORR was 23.5% (4/17) while the DCR was 94.1% (16/17). The estimated median PFS was 5.9 months (not mature). The most common Grade 3 adverse events (AEs) were hand-foot syndrome (13.6%), myelosuppression (4.5%) and constipation (4.5%), and no Grade4/5 observation. There were no unexpected treatment-related AEs (TRAES).

Conclusions

This recent analysis of the ALTER-L024 study demonstrates the encouraging clinical benefit and manageable safety profile of anlotinib plus docetaxel in patients who progressed on previous chemotherapy.

Clinical trial identification

NCT03732001.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Brain metastasis is one of the significant problems in patients with lung cancer. Most of the patients are asymptomatic at presentation. Prognosis and survival in these patients are lacking. Many studies that looked upon the incidence of brain metastasis at the presentation of NSCLC are retrospective. In India, brain metastasis frequency in patients with NSCLC at the presentation has not been well studied. This study has been planned to evaluate the incidence of brain metastasis in NSCLC patients treated in our center.

Methods

It is a prospective observational study conducted in medical oncology at our tertiary care center from Sep 2019- Sep 2020. A total of 150 patients with lung cancer were registered in the department. Among them, 112 patients had advanced non-small cell carcinoma of the lung (NSCLC), and they were enrolled in the study. MRI brain was taken at the time of diagnosis.

Results

The mean age at presentation was 60 years. The Median follow-up was 15 months. Median overall survival in the study was 11 months. Patients with brain metastasis had a median survival of 7 months, whereas patients without brain metastasis had 13 months. Clinical profile, performance status, demographic characteristics, and imaging findings were noted at the presentation time and the results were analyzed as follows.

Conclusions

The study period is short, so that data on molecular abnormalities in patients with brain metastasis was not included in the data. Our study found that female patients were at higher risk for brain metastasis. Other risk factors were adenocarcinoma histology and age less than 60 years. There are no biomarkers to predict brain metastasis in NSCLC due to its molecular heterogeneity. The study will serve as a baseline platform of clinical predictors of brain metastasis in NSCLC. Our future direction and research will be clinical predictors along with molecular driver mutations in NSCLC in detecting brain metastasis.

Legal entity responsible for the study

Rajiv Gandhi Government General Hospital, Madras Medical College.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.