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Advanced NSCLC

128P - A real world scenario of applicability of Immuno Oncology agents into practice in NSCLC in a resource constrained setting

Room
ePoster Display
Speakers
  • S. G (New delhi, India)
Authors
  • S. G (New delhi, India)
  • M. Singhal (New delhi, India)
  • A. Sharma (New delhi, India)
  • S. Valame (New delhi, India)
  • D. Panda (New delhi, India)

Abstract

Background

Non-small cell lung cancer is one cancer which has seen radical change in treatment in the last decade with the advent of immunotherapy and targeted therapies. Chemo immunotherapy has increased the survival multi fold in metastatic setting and also in earlier lines and is the first line treatment now in non driver mutation setting. However, applicability of the same into real world practice has been dismal in low and middle income countries due to various reasons. Data is lacking in this setting.

Methods

We conducted a prospective observational study to see the applicability of Immuno Oncology drug indications in stage 3 and 4 NSCLC patients. Consecutive patients between March 2018 and February 2020 who had an approved indication for IO regimen usage were included. Stage 3b and 3c and stage 4 driver mutation negative patients were taken into the study. Their treatment regimens were studied and reasons for non usage of IO regimen were assessed.

Results

Between March 2018 and February 2020, 88 patients were enrolled who were eligible for treatment with IO agents in NSCLC. Among them, stage 3b were 9%, stage 3c were 11.3% and stage 4 were 79.7% patients. Only 30 patients (34%) could receive IO agents in their treatment regimen across various lines of therapy. In stage 4 NSCLC,35.7% patients were treated with IO agents either in the 1st line or later lines. In stage 3, 5 of 18 patients went on to receive IO agent post definitive chemo radiation. The most common reason for non usage of IO agents were financial constraints (68.9%) including exhaustion of insurance limit, denial by insurance company (20.6%) and non availability of drug (10.5%). Of 30 patients who received IO agents, 8 patients had to withdraw owing to financial toxicity while they were still responding with average time to withdrawal being 7.2 months.

Conclusions

This observational study depicts the real world scenario of the difficulties in bringing approved regimen into practice with financial toxicity being the reason the non usage in nearly 60% patients. In low income countries, this needs to be addressed if more number of patients are to be benefitted from IO agents in NSCLC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Advanced NSCLC

129P - Predicting response to immunotherapy in advanced Non-Small-Cell Lung Cancer

Room
ePoster Display
Speakers
  • M. Rebordão Pires (Coimbra, Portugal)
Authors
  • M. Rebordão Pires (Coimbra, Portugal)
  • C. De Sousa Amorim Sampaio da Costa (Coimbra, Portugal)
  • T. Cunha Pereira (Coimbra, Portugal)
  • J. Monteiro (Coimbra, Portugal)
  • I. Domingues (Coimbra, Portugal)
  • A. Caetano (Coimbra, Portugal)
  • A. Meira Garcia (Coimbra, Portugal)
  • E. Jesus (Coimbra, Portugal)
  • G. Sousa (Coimbra, Portugal)

Abstract

Background

The advanced Non-Small Cell Lung Cancer's (aNSCLC) response to immunotherapy (IO) is heterogenous, thus biomarkers to predict response are needed. EPSILoN and NLCIPS (Non-Small Cell Lung Cancer Immunotherapy Prognosis Score) are two predictive models which help to identify aNSCLC patients who will benefit from IO.

Methods

We conducted a retrospective, single-center study of aNSCLC patients who had received IO, between January 2016 and December 2020. The primary endpoint was progression-free survival (PFS) and its correlation with each score. EPSILoN combines five baseline clinical/blood parameters: ECOG/PS, smoking, liver metastases, LDH and neutrophil-to-lymphocyte ratio (NLR). EPSILoN stratified patients in good, intermediate or poor responders to IO. NLCIPS is a response predictive model based in smoking index and NLR, which stratifies patients in 4 groups on 1-year-PFS: very poor, poor, intermediate and good. Descriptive statistical analysis, survival analyses with Kaplan-Meier curves and multivariate analyses with cox regression model were made using SPSS®.

Results

We analyzed 70 patients, 68,6% male, median age 62,5 years (38–81 years), 57,1% smokers, 57,1% stage IV and 27% expressed PD-L1³50%. Using EPSILoN score patients were stratified in good 25,7%; intermediate 67,14%; and poor 7,1%. Using NLCIPS predictive model patients were stratified in 4 groups according to predicted 1-year-PFS: very poor (1-year PFS <0,1) in 18,57%; poor (1-year PFS 0,18) in 27,14%; intermediate (1-year PFS 0,28) in 25,7%; and good (1-year PFS >0,6) in 28,6%. The median follow-up was 8,5 months. Median PFS was 4 months (0–56 months), with statistical significance differences in PFS between groups either applying EPSILoN (p = 0,003) or NLCIPS score (p = 0,008). The multivariate analysis with cox regression, showed a statistically significant difference in PFS using EPSILON score (HR 3,05 [CI 95% 1,24–7,46], p = 0,015), NLCIPS (HR 0,595 [CI 95% 0,4–0,89], p = 0,010) and PD-L1³50% (HR 0,247 [CI 95% 0,09–0,68], p = 0,007).

Conclusions

Our study shows that stratifying aNSCLC patients using either EPSILON or NLCIPS score can help to identify who will most likely benefit from IO. Further studies are warranted.

Legal entity responsible for the study

Portuguese Institute for Oncology of Coimbra.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Advanced NSCLC

130P - Neutrophil-to-lymphocyte ratio as a response predictor to immune checkpoint inhibitors in non-small-cell lung cancer

Room
ePoster Display
Speakers
  • C. De Sousa Amorim Sampaio da Costa (Coimbra, Portugal)
Authors
  • C. De Sousa Amorim Sampaio da Costa (Coimbra, Portugal)
  • M. Rebordão Pires (Coimbra, Portugal)
  • J. Monteiro (Coimbra, Portugal)
  • A. Caetano (Coimbra, Portugal)
  • F. Salgueiro (Coimbra, Portugal)
  • J. Correia Magalhães (Coimbra, Portugal)
  • M. De Sousa (Coimbra, Portugal)
  • R. Basto (Coimbra, Portugal)
  • A. Meira Garcia (Coimbra, Portugal)
  • I. Domingues (Coimbra, Portugal)
  • E. Jesus (Coimbra, Portugal)
  • G. Sousa (Coimbra, Portugal)

Abstract

Background

The immune checkpoint inhibitors (ICIs) have changed the treatment of non-small cell lung cancer (NSCLC) but there are few predictive and prognostic biomarkers. Even with high levels of PD-L1 expression, some patients do not benefit from anti-PD1 or PD-L1 inhibitors. Neutrophil-to-lymphocyte ratio (NLR) has been shown to be a potential biomarker in these settings.

Methods

The primary endpoint was to evaluate NLR relation with progression-free survival (PFS) and overall survival (OS). Secondary endpoints were analysis of population demographics and major toxicities to ICIs. Unicentric, retrospective clinical study, including all patients with advanced NSCLC treated with ICIs. NLR is calculated by dividing the absolute neutrophil count by the absolute lymphocyte count from a complete blood count with differential. NLR was defined as high when > 2,375 and low when ≤ 2,375, using ROC curve. PFS was calculated by the Kaplan-Meier method.

Results

Sixty-nine patients treated with ICIs from January 2016 until October 2020 were analysed, with median age of 63 years old, 66.7% were males, 33.3% non-smokers, 62.3% had an ECOG PS 0, and 58% had stage IV at diagnosis. Thirty-two (46.4%) patients were receiving ICIs as second line treatment. Thirty-three patients (47.8) received pembrolizumab, thirty-two (46.4%) nivolumab and four (5.8%) atezolizumab. The median number of treatments of ICIs were 9 (1–105). Median PFS was 7 months (3.0–10.9), with no significative statistical differences between the high and low NLR groups. Median PFS of patients treated with nivolumab was 3 months (1.9–4.1), with pembrolizumab was 15 months (4.7–25.3) and with atezolizumab was 3 months. Immunomediated adverse events (AEs) G3/4 were present in 6 patients and required ICIs suspension in all cases. One toxic death with pembrolizumab (1 cycle) was observed after hepatic failure.

Conclusions

Our results were probably due to small population in this study and it is crucial to search for biomarkers to predict ICIs response. These biomarkers will help to define which patients will benefit the most from these therapeutics.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Advanced NSCLC

131P - Predictive factors of response to PD-(L)1 inhibitors in patients with advanced non-small cell lung (NSCLC) and high PD-L1 expression

Room
ePoster Display
Speakers
  • A. Barba Joaquín (Barcelona, Spain)
Authors
  • A. Barba Joaquín (Barcelona, Spain)
  • A. Piedra (Barcelona, Spain)
  • J. Mosquera (a Coruña, Spain)
  • M. Riudavets Melià (Villejuif, France)
  • M. Gomez-Randulfe (a Coruña, Spain)
  • M. Garcia Campelo (A Coruña, Spain)
  • I. Sullivan (Barcelona, Spain)
  • J. Serra (Barcelona, Spain)
  • M. Aguado (Barcelona, Spain)
  • M. Majem Tarruella (Barcelona, Spain)

Abstract

Background

Tumor PD-L1 expression is the only biomarker predictive of responsiveness in advanced NSCLC treated with PD-(L)1 inhibitors. Analysis of PD-L1 expression by IHC has been validated in histological samples. Smoking and overweight have been described as predictive factors of better outcome, whereas bone metastases,antibiotic, corticosteroids and proton pump inhibitors as predictive factors of poor outcome. The aim of our study was to analyze potential predictive factors of response to PD-(L)1 inhibitors in patients (pts) with advanced NSCLC and high PD-L1 expression.

Methods

The study was carried out in pts with advanced NSCLC and high PD-L1 expression treated with PD-(L)1 inhibitors. Clinical and histological variables of interest were registered. Kaplan-Meier estimations were used to calculate survival, and log-rank test to make comparisons. The impact of variables on survival was assessed through univariate and multivariate analysis. We present preliminary results of the analysis.

Results

86 pts were included in the analysis. Mean age was 66 y [36–84], 21 (24.4%) were females, 73.3% former smokers and 22.1% current smokers, 38,4% presented normal BMI, 79% had non-squamous NSCLC, 85% received PD-(L)1 inhibitors in first line and 12% pts had cytological sample for PD-L1 determination. 72 (84%) pts received monotherapy with PD-(L)1 inhibitor, 4 (5%) pts CT plus PD-(L)1 inhibitor and 10 (11.6%) pts received PD-(L)1 inhibitors with other immunotherapy. The mean OS and PFS were 14.1 and 9.6 months, respectively. ORR and DCR in overall patients were 57% and 72.7%, respectively and ORR and DCR in pts treated in first line were 57.6% and 73.4%, respectively. Better results were detected in overweight and in smoker pts despite not being estatistically significant. A trend to worse OS was observed in pts with bone metastasis. No differences in OS were observed according to the type of tumor sample (cytological and histological samples).

Conclusions

Preliminary results showed that smoking and overweight could be potential predictive factors of better outcome withe bone metastasis potential predictive factors of poor outcome, and no differences in survival were observed according to the type of tumor sample.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Barba Joaquín: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Travel/Accommodation/Expenses: Merk; Speaker Bureau/Expert testimony: Bristol; Speaker Bureau/Expert testimony: Angelini. M. Riudavets: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Merk. M.R. Garcia Campelo: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merk; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Speaker Bureau/Expert testimony: Boehringer; Speaker Bureau/Expert testimony: AstraZeneca. I.G. Sullivan: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merk; Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: AstraZeneca. M. Majem Tarruella: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Boehringer; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Pfizer. All other authors have declared no conflicts of interest.

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Advanced NSCLC

132P - Stage IV Non-small cell lung cancer stage in the elderly - Real World Data

Room
ePoster Display
Speakers
  • J. Monteiro (Coimbra, Portugal)
Authors
  • J. Monteiro (Coimbra, Portugal)
  • C. De Sousa Amorim Sampaio da Costa (Coimbra, Portugal)
  • M. Rebordão Pires (Coimbra, Portugal)
  • A. Caetano (Coimbra, Portugal)
  • F. Salgueiro (Coimbra, Portugal)
  • I. Domingues (Coimbra, Portugal)
  • A. Meira Garcia (Coimbra, Portugal)
  • E. Jesus (Coimbra, Portugal)
  • N. Bonito (Coimbra, Portugal)
  • G. Sousa (Coimbra, Portugal)

Abstract

Background

Lung cancer is commonly diagnosed at an advanced stage and older age, therefore an increasing number of elderly patients are being considered for systemic treatment. Platinum-based chemotherapy (CT) is a viable option for fit patients, while single-agent CT is an alternative for selected patients, and immunotherapy and targeted therapy are recommended when indicated. However, the elderly are a complex and heterogeneous population, that remain a challenge for oncologists in the real world.

Methods

We conducted a retrospective study to compare younger (<70 years) and older (≥70 years) patients with stage IV Non-Small Cell Lung Cancer (NSCLC), regarding treatment choices and overall survival (OS), being these two the primary endpoints. The secondary endpoints were to describe and compare the two groups, to assess which characteristics were associated with poor prognosis, and to evaluate the occurrence of grade 3–4 toxicities.

Results

We included 118 patients with a newly diagnosed stage IV NSCLC discussed and oriented in a Multidisciplinary Meeting at our institution between January of 2017 and December of 2019, divided into group A (<70 years) (n = 70) and group B (≥70 years) (n = 48). There was a statistically significant difference regarding the the Eastern Cooperative Oncology Group Performance Status (ECOG PS) (p = 0.005) and molecular target (p = 0.04), with group B having higher ECOG PS values and higher prevalence of EGFR mutation over ALK. Factors such as having brain (HR: 2.172; 95% IC: 1.209–3.905; p = 0.01) or bone (HR: 1.856; 95% IC: 1.060–3.251; p = 0.03) metastasis or not undergoing systemic treatment (HR: 9.191; 95% IC: 4.496–18.788; p < 0,001) showed negative influence on OS. Only 63,6% (n = 75) of the patients underwent systemic treatment. In these patients there was a difference regarding the chosen 1st line treatment (p = 0.02), with a higher prevalence of the platinum-based doublet CT in the group A vs B (61% vs 42%), at the expense of a lower prevalence of single-agent CT (8% vs 27%, respectively). There were no significant differences concerning OS or incidence of grade 3–4 toxicities.

Conclusions

Age should not be a decisive factor for the realization of systemic treatment. A personalized and appropriate choice of treatment can improve compliance and tolerance, without detriment to survival.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Advanced NSCLC

133P - Drug - drug interactions (DDIs) in non-small cell lung cancer during chemotherapy - immunotherapy treatment

Room
ePoster Display
Speakers
  • M. Occhipinti (Milan, Italy)
Authors
  • M. Occhipinti (Milan, Italy)
  • M. Brambilla (Milan, Italy)
  • G. Galli (Milan, Italy)
  • S. Manglaviti (Milan, Italy)
  • A. Prelaj (Milan, Italy)
  • R. Ferrara (Milan, Italy)
  • A. De Toma (Milan, Italy)
  • T. Beninato (Milan, Italy)
  • E. Zattarin (Milan, Italy)
  • C. Proto (Milan, Italy)
  • G. Lo Russo (Milan, Italy)
  • A. Gelibter (Rome, Italy)
  • M. Simmaco (Rome, Italy)
  • M. Garassino (Chicago, IL, United States of America)
  • P. Marchetti (Rome, Italy)

Abstract

Background

Polypharmacotherapy is a relevant issue in cancer patients, since the onset of a drug-drug Interaction (DDI) may affect both treatment efficacy and toxicity. Immune checkpoint inhibitors (ICIs) have rekindled the interest in DDIs beyond pharmacodynamic and pharmacokinetic considerations. Concomitant drugs (CDs), such as steroids, proton pump inhibitors and antibiotics can influence the clinical efficacy of ICIs. Here we present the use of Drug-PIN® (Personalized Interactions Network) software in non-small cell lung cancer (NSCLC) patients undergoing chemo-immunotherapy (CHT - ICI). Drug-PIN® is the first intelligent system that recognizes the critical role of multiple interactions between active and/or pro-drug forms by integrating biochemical, demographic, and genomic data of 110 SNPs from each patient.

Methods

From January 2020 to September 2020 we enrolled patients with (1) Stage IV NSCLC candidate to receive CHT - ICI (platinum salts - pemetrexed - pembrolizumab); (2) ECOG PS 0–2; (3) taking at least 1 concomitant drug; Toxicities were graded according to CTCAE v5.0. Oncologic treatments, CDs, clinical and laboratory data were collected and inserted in Drug-PIN ®.

Results

Forty-two patients, with a median age of 63 years (range 35–82) and with a male/female ratio of 22/20, were included. Eight clinically relevant DDIs with a need for medical intervention in a total of 6 patients (14%) were identified; the 3 major DDIs were related to a medium grade interaction between pemetrexed and NSAIDs. Thirty-five patients showed at least one toxicity of any grade, of which 15 with grade ≥ 3. Nineteen patients showed at least one immune related adverse event. We identified a statistically significant association between the use of antiaggregant/anticoagulants (p = 0.01 odds ratio 5.52, 95% CI 1.23–30.66) and opioids (p = 0.02 odds ratio 5.43, 95% CI 1.1–37.23) and non-response to treatment.

Conclusions

This is the first retrospective study assessing the prevalence of DDIs, the clinical need for medical intervention and the impact of concomitant drugs on CHT - ICI efficacy in NSCLC patients. Drug-PIN® could be useful in the era of personalized medicine to prevent severe adverse events and improve survival in cancer patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

G. Lo Russo: Honoraria (institution): Lilly; Honoraria (institution): BMS; Honoraria (institution): AstraZeneca. M.C. Garassino: Honoraria (institution): AstraZeneca; Honoraria (institution): Lilly; Honoraria (institution): Pfizer; Honoraria (institution): BMS; Honoraria (institution): MSD. All other authors have declared no conflicts of interest.

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Advanced NSCLC

134P - Effectiveness of Immune Checkpoint Inhibitor monotherapy for postoperative recurrent Lung Cancer in clinical practice

Room
ePoster Display
Speakers
  • T. Sasaki (Sendai, Japan)
Authors
  • T. Sasaki (Sendai, Japan)
  • N. Yoshimura (Sendai, Japan)

Abstract

Background

There are few clinical trials and literature reports investigating the effects of immune checkpoint inhibitors (ICIs) specialized in the treatment of postoperative recurrent lung cancer.To investigate the specific efficacy of ICI monotherapy in postoperative recurrent lung cancer.

Methods

We retrospectively studied the treatment results of 82 cases of postoperative recurrent lung cancer (non-small cell lung cancer) who received ICI monotherapy in our department. We extracted factors that contribute to response and survival and examine the efficacy and safety of three types of ICI for postoperative recurrent lung cancer.

Results

I. Nivolumab (n = 37) has a 3-year survival rate of 26% and a disease control rate of 61%, which is comparable to clinical trials for advanced/recurrent lung cancer, and is particularly good for the elderly and patients with poor performance status. It seemed to be adaptive. II. Pembrolizumab (n = 29) had a 2-year survival rate of 71%, a response rate of 34%, and a disease control rate of 66%, which were as good as those in clinical trials. III. Atezolizumab (n = 16) had a particularly low response rate with a 1-year survival rate of 85%, a response rate of 19%, and a disease control rate of 56%. The prognosis of the driver gene mutation case was significantly poor (p = 0.01). In the overall multivariate analysis, gene mutation-positive cases had a significantly poor prognosis (p = 0.02, HR = 0.34).

Conclusions

The anti-PD-1 antibody drug performed better than the anti-PD-L1 antibody drug. In addition, the effectiveness of ICI administration for postoperative recurrent lung cancer could be shown as a feature of this study. The number of cases and analysis data will be updated and reported at the meeting.

Legal entity responsible for the study

Ethics Committee of Tohoku Medical and Pharmaceutical University Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Advanced NSCLC

135P - The real-world use of Tyrosine Kinase Inhibitors (TKIs) in Epidermal Growth Factor Receptor mutated (EGFRm) advanced (stage IIIb / IIIc / IV) Non-Small Cell Lung Cancer (NSCLC) patients

Room
ePoster Display
Speakers
  • J. Subramanian (Kansas City, MO, United States of America)
Authors
  • J. Subramanian (Kansas City, MO, United States of America)
  • Y. Choi (Seoul, Korea, Republic of)
  • T. Chou (Taipei, Taiwan)
  • J. Gregg (Davis, CA, United States of America)
  • R. Hui (Sydney, NS, Australia)
  • N. Leighl (Toronto, ON, Canada)
  • A. Marchetti (Chieti, Italy)
  • N. Navani (London, United Kingdom)
  • T. Bailey (Bollington, United Kingdom)
  • M. Silvey (Bollington, United Kingdom)
  • R. Makin (Bollington, United Kingdom)
  • D. Kahangire (Cambridge, United Kingdom)
  • M. Chau (Gaithersburg, MD, United States of America)
  • A. Taylor (Cambridge, United Kingdom)
  • F. Griesinger (Oldenburg, Germany)

Abstract

Background

Given the role of EGFRm in the development of NSCLC, EGFR is an established target for treating the disease. While EGFR-TKIs are the recommended first-line (1L) treatment option for advanced EGFRm NSCLC, there is limited evidence describing the use of EGFR-TKIs in clinical practice. This study investigated the real-world treatment patterns in advanced EGFRm NSCLC patients.

Methods

A physician survey and retrospective medical chart review conducted in Australia, Canada, Germany, Italy, South Korea, Taiwan, UK and USA (May – Aug 2020) included 223 physicians and provided data on 1,793 advanced NSCLC patients who received a positive first EGFR test result between Jan – Dec 2017, with data on patient demographics, clinical characteristics, and testing and treatment patterns abstracted from diagnosis until Mar 2020 (or death).

Results

Median age at advanced diagnosis was 65 years, 54% were male; 17% had a family history of lung cancer. 56% of patients were either smokers or ex-smokers (median pack years: 35); 31% had never smoked. 84% had advanced NSCLC at presentation. 39% received ≥ 1 treatment prior to EGFRm result, with 14% receiving an EGFR TKI pre EGFRm result. Following receipt of EGFRm test result 88% of patients initiated ≥ 1 treatment line; 67% of sample initiated EGFR TKIs as 1L “post EGFRm result” treatment (52–86% between countries); 73% received an EGFR-TKI “pre” or 1L “post” EGFRm result. 56% of patients received a 1L “post EGFRm result” EGFR TKI alone; 9% received in combination with chemotherapy. 80% of patients overall received an EGFR TKI at any line, pre or post confirmation of EGFRm status (range 73–94% between countries).

Conclusions

Just under three quarters of patients received an EGFR-TKI either prior to EGFRm test result, or in the 1L “post EGFRm result” setting, indicating that while the majority of patients received targeted therapy, over a quarter of patients with confirmed EGFRm status may have received sub-optimal treatment. The geographical variations in 1L EGFR-TKI use observed between countries suggests variability in the adoption and implementation of optimal testing and treatment in this population.

Editorial acknowledgement

Medical writing support under the guidance of the authors was provided by Gary Sidgwick of Adelphi Real World, on behalf of Adelphi Real World and AstraZeneca, and was funded by AstraZeneca in accordance with Good Publication Practice (GPP3) guidelines.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

J. Subramanian: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Boehringer-Ingelheim; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Ely Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: Cardinal Health. Y-L. Choi: Research grant/Funding (institution): AstraZeneca. J. Gregg: Shareholder/Stockholder/Stock options, Full/Part-time employment: Freenome; Speaker Bureau/Expert testimony: AstraZeneca. R. Hui: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy: Ely Lilly; Honoraria (self), Advisory/Consultancy: Merck Sharp and Dohme; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Seagen. N. Leighl: Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca. N. Navani: Honoraria (self): BMS; Honoraria (self): Pfizer; Honoraria (self): Takeda; Honoraria (self), Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Amgen; Advisory/Consultancy: Olympus. D.A. Kahangire: Full/Part-time employment: AstraZeneca. M. Chau: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca; Shareholder/Stockholder/Stock options: Roche. A. Taylor: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. F. Griesinger: Advisory/Consultancy: Roche; Advisory/Consultancy: Boehringer-Ingelheim; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Novartis; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Takeda; Advisory/Consultancy: Merck Sharp & Dohme. All other authors have declared no conflicts of interest.

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Advanced NSCLC

136P - Best practice recommendations for molecular analysis of acquired EGFR TKI resistance mechanisms

Room
ePoster Display
Speakers
  • L. Hondelink (Leiden, Netherlands)
Authors
  • L. Hondelink (Leiden, Netherlands)
  • D. Cohen (Leiden, Netherlands)
  • J. Von der Thüsen (Rotterdam, Netherlands)
  • E. Dubbink (Rotterdam, Netherlands)
  • T. Van Wezel (Leiden, Netherlands)
  • K. Monkhorst (Amsterdam, Netherlands)

Abstract

Background

With the approval of first line osimertinib treatment in stage IV EGFR mutated NSCLC, detection of potentially targetable resistance mechanisms will become increasingly important - and complex. Clear guidelines on how to test effectively for the wide variety of molecular alterations that occur after EGFR-TKI resistance are currently lacking. Between pathology labs worldwide there is considerable divergence with respect to work-up strategies for resistance mechanism detection, potentially leading to incomplete analyses in which treatable targets can be missed. By retrospectively analyzing the yield of different testing modalities in 323 cases from three tertiary referral hospitals in the Netherlands, we provide ‘best practice’ recommendations for optimal molecular diagnostics in the post-EGFR TKI resistance setting.

Methods

Molecular work-up strategies were compared in 162 first and second generation TKI treated cases (early-TKI group) and 161 osimertinib treated cases (osimertinib group). Laboratories made use of combinations of DNA-NGS, RNA-NGS, ISH and immunohistochemical techniques. In total, a resistance mechanism was identified in 72 early-TKI cases (50%) versus 78 osimertinib cases (52%).

Results

RNA-NGS revealed relevant extra information in 4% of early-TKI cases and 10% of osimertinib cases. Co-occurrence of fusions and exon skipping events with any other resistance mechanism detected by DNA-NGS or ISH occurred in four out of eight cases (50%). Amplifications in HER2 and MET were detected in 12 (12%) of early-TKI cases and 23 (17%) of osimertinib cases. MET- and HER2 ISH revealed relevant extra information in 14 cases. In 11 cases (31% of all MET and HER2 amplifications), the amplification was exclusively detected in ISH or IHC, but was missed in DNA-NGS, especially in cases with low tumor-cell percentage.

Conclusions

Our data support a ‘best practice’ method for molecular diagnostics in the current practice EGFR TKI resistance setting that includes DNA-NGS, RNA-NGS, MET ISH and either HER2 ISH or IHC. As resistance mechanisms co-occur and fusions and exon-skipping are not mutually exclusive events, we advise against using a sequential or more selective approach.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

J. von der Thüsen: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche Diagnostics. E.J. Dubbink: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Pfizer; Advisory/Consultancy: PGDx. T. Van Wezel: Research grant/Funding (institution), Research grant was not for this study: ArcherDX. K. Monkhorst: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Speakers fee: AstraZeneca; Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies, Speakers fee: Roche; Honoraria (self), Advisory/Consultancy, Speakers fee: MSD; Honoraria (self), Speakers fee: Benecke; Advisory/Consultancy, Non-remunerated activity/ies: Pfizer; Advisory/Consultancy: BMS; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Diaceutics; Advisory/Consultancy: Lilly; Advisory/Consultancy: Bayer; Advisory/Consultancy: Boehringer Ingelheim; Non-remunerated activity/ies: Takeda; Non-remunerated activity/ies: PGDx; Non-remunerated activity/ies: Delfi. All other authors have declared no conflicts of interest.

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Advanced NSCLC

137P - Epidermal Growth Factor Receptor mutation status and response to Tyrosine Kinase Inhibitors in advanced Chinese female lung squamous cell carcinoma: a retrospective study

Room
ePoster Display
Speakers
  • Q. Chang (Shanghai, China)
Authors
  • Q. Chang (Shanghai, China)
  • H. Qiang (Shanghai, China)
  • C. Tianqing (Shanghai, China)

Abstract

Background

The frequency of epidermal growth factor receptor (EGFR) mutations and the efficacy of tyrosine kinase inhibitor (TKI) in Chinese female patients with lung squamous cell carcinoma (SCC) are unknown. This study was designed to investigate the incidence of EGFR mutations and the role of targeted therapy in advanced Chinese female lung SCC patients.

Methods

Advanced female patients diagnosed with lung SCC at the Shanghai Chest Hospital between January 2013 and December 2018 were retrospectively analyzed.

Results

A total of 4223 advanced lung SCC patients were screened, and there were 154 female lung SCC patients who had underwent EGFR mutation detection. Positive EGFR mutations were found in 29.9% (46/154) of female lung SCC patients, including twenty-three 19del mutation (14.9%), twenty-one 21L858R mutation (13.6%) and other mutations (1.4%, 21861Q and 20ins). For 45 EGFR positive mutation female SCC patients, the median progression-free survival (PFS) of patients who received EGFR-TKI therapy (n = 38) was 8.0 months (95% CI, 5.4–10.7 months), which was significantly longer than patients who were treated with chemotherapy (8.0 vs 3.2 months, p = 0.024), and the median overall survival (OS) was also longer (24.9 months vs 13.9 months, p = 0.020). The objective response rate (ORR) was 44.7% (17/38), and the disease control rate (DCR) was 81.6% (31/38). For 105 female SCC patients with EGFR negative mutation, the median OS was 18.6 months (95% CI, 14.2–22.9 months) and it was no different from that of EGFR positive mutation patients (18.6 vs 22.8 months, p = 0.377).

Conclusions

For advanced Chinese female lung SCC patients with EGFR positive mutations, targeted therapy could confer longer PFS and OS than chemotherapy, but the survival was similar with patients who were negative EGFR mutations.

Legal entity responsible for the study

The authors.

Funding

The Western Medicine Guide Project of the Shanghai Committee of Science and Technology.

Disclosure

All authors have declared no conflicts of interest.

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Advanced NSCLC

138P - The impact of variant allele frequency in EGFR mutated NSCLC patients on targeted therapy

Room
ePoster Display
Speakers
  • A. Addeo (Geneva, Switzerland)
Authors
  • A. Addeo (Geneva, Switzerland)
  • A. Friedlaender (Geneva, Switzerland)
  • M. Chevallier (Geneva, Switzerland)
  • C. De Vito (Geneva, Switzerland)
  • P. Tsantoulis (Geneva, Switzerland)

Abstract

Background

Allelic frequency, or the variant EGFR allele frequency, corresponds to the fraction of sequencing reads harbouring the mutation. The allelic fraction is influenced by the proportion of tumour cells in the sample, the presence of copy number alterations but also, most importantly, by the proportion of cells within the tumour that carry the mutation. Mutations that occur early in tumour evolution, often called clonal or truncal, have a higher allelic frequency than late, subclonal mutations, and are more often drivers of cancer evolution and attractive therapeutic targets. Most, but not all, EGFR mutations are clonal. We hypothesized that tumours with low allelic frequency of the EGFR mutation will respond less favourably to targeted treatment.

Methods

We identified all patients treated with front-line TKIs (gefitinib, erlotinib, afatinib, osimertinib) in our centre for advanced EGFR mutated NSCLC between January 2016 and January 2020. We identified 42 patients. OS was primary endpoint and PFS secondary. Patient characteristics included sex, age at diagnosis, smoking status, performance status (PS) and presence of brain metastases at diagnosis.

Results

The median allelic frequency of the EGFR mutation was 0.47. We used a simple cut-off of 0.30 to separate low from high allelic frequency, as a surrogate marker of early, clonal mutations versus late, subclonal mutations. High EGFR mutation allelic frequency was associated with longer PFS (HR 0.27, 95% 0.09–0.79, P = 0.017). igh allelic frequency was not associated with significant difference in OS (HR 0.47, 95% 0.17–1.30, P = 0.14), Sensitive tumours were associated with significantly longer PFS (HR 0.22, 95% 0.07–0.61, P = 0.004) and OS (HR 0.35, 95% 0.13–0.90, P = 0.029). 1yOS was 10% in the insensitive group, compared with 79% in the sensitive group. Patients with insensitive tumours were almost 10 times more likely to die before 12 months than patients with sensitive tumours (Fisher's test OR 9.7, P = 0.007).

Conclusions

The mutant allelic frequency of EGFR in NSCLC appears to be associated with clinical outcomes among patients treated with TKIs. By combining the latter with variant allelic frequency, we identify two clear prognostic groups, resistant and sensitive patients to TKIs.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Addeo: Honoraria (self): BMS; Honoraria (self): Merck; Honoraria (self): Astellas; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): AstraZeneca. A. Friedlaender: Honoraria (self): BMS; Honoraria (self): Merck; Honoraria (self): Astellas. All other authors have declared no conflicts of interest.

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Advanced NSCLC

139P - The impact of TP53 mutations on EGFR mt+ NSCLC IV patients treated with 3rd generation TKI on 2nd line or further line therapy - Real world data from two certified lung cancer centers in Germany

Room
ePoster Display
Speakers
  • J. Roeper (Oldenburg, Germany)
Authors
  • J. Roeper (Oldenburg, Germany)
  • P. Christopoulos (Heidelberg, Germany)
  • M. Falk (Hamburg, Germany)
  • L. Heukamp (Hamburg, Germany)
  • A. Stenzinger (Heidelberg, Germany)
  • M. Thomas (Heidelberg, Germany)
  • F. Griesinger (Oldenburg, Germany)

Abstract

Background

TP53 co-mutations are frequent in EGFR mt+ NSCLC and have a strong negative impact on all clinical endpoints in 1st and 2nd generation TKI therapy. However, it is unclear, whether TP53 mutations also have an impact on the effectiveness of 3rd generation TKI. Therefore, we retrospectively analyzed the impact of TP53 co-mutations on PFS and OS in a cohort of EGFR mt+ NSCLC IV patients (UICC 7/8) who developed T790M resistance to 1st and 2nd generation TKI and were treated with 3rd generation TKI in 2nd or further line.

Methods

77 EGFR mt+ NSCLC IV patients tested for TP53 co-mutations and showing a T790M resistance mechanism against 1st or 2nd generation TKI were treated with 3rd generation TKI (Osimertinib) in 2nd or further lines. The endpoints PFS and OS were investigated in the TP53mt+ vs. TP53WT groups for only 2nd line (24 TP53 mt+ vs. 27 TP WT) and for the complete population (2nd and further line).

Results

Baseline characteristics of the 77 EGFR mt+ NSCLC IV patients: median age was 64 years (28–92 years), 65% were female (n = 50/77), 71.4% were never/light smoker (n = 55/77) and 9% had an ECOG of 0 or 1 (n = 70/77). 32/77 (42%) had a TP53 mutation, 45/77 (58.4%) were TP53 WT. Median PFS of 3rd generation TKI in 2nd line was 9 (n = 24) vs. 13 months (n = 27) for TP53 mt+ vs. WT (HR 0.499; p < 0.042). Median PFS of 3rd generation TKI in 2nd and further lines was 9 (n = 32) vs. 14 (n = 45) months for TP53 mt+ vs. WT (HR 0.502; p < 0.012). Median OS of 3rd generation TKI in 2nd and further lines was 16 vs. 24 months for TP53mt+ (n = 32) vs. WT (n = 45) (HR 0.561; p < 0.031).

Conclusions

TP53 co-mutations have a negative impact on PFS and OS in EGFR mt+ NSCLC IV patients treated with 3rd generation TKI (Osimertinib) in 2nd line and 2nd/further lines. Thus, p53 is a negative predictor in EGFR mt+ NSCLC patients treated with Osimertinib. TP53 might be an important target to drug in EGFR mt+ NSCLC in combination with Osimertinib.

Legal entity responsible for the study

University Hospital Internal Medicine-Oncology, Pius Hospital Oldenburg, University Oldenburg.

Funding

Has not received any funding.

Disclosure

J. Roeper: Honoraria (self): Boehringer Ingelheim; Honoraria (self): AstraZeneca; Honoraria (self): Roche. P. Christopoulos: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy, Research grant/Funding (self): Roche; Advisory/Consultancy, Research grant/Funding (self): Takeda; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Chugai; Advisory/Consultancy: Pfizer. M. Falk: Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self): AstraZeneca; Honoraria (self): Roche; Advisory/Consultancy: Pfizer. L.C. Heukamp: Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Siemens. M. Thomas: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: Takeda; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Celgene; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche. F. Griesinger: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Siemens; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Takeda; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AbbVie. All other authors have declared no conflicts of interest.

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