FP03.03 ECOG PS of 0-1 and Very High PD-L1 Expression ≥90% Are Associated With Clinical Benefit From First-Line Chemo-Immunotherapy in Advanced NSCLC

Background: EGFR TKIs have shown first-line efficacy in EGFRm+ NSCLC but acquired resistance is inevitable; with afatinib, this is predominantly through the emergence of T790M. Therefore, a key consideration when assessing therapeutic choices is the availability of subsequent treatment options. The GioTag study (NCT03370770) is the first to assess outcomes of real-world patients (Pts) who received first-line afatinib followed by osimertinib; for pts with EGFRm+ NSCLC and acquired T790M this sequence resulted in a median time on treatment (ToT) of 27.6 months, which did not include chemotherapy. We present subgroup analyses of pts from the GioTag study who are under-represented in randomized controlled trials (RCTs) and assess the impact of afatinib treatment on ECOG PS. Methods: The GioTag study is an observational, multicenter study. Data were collected retrospectively (Dec 2017–May 2018). Pts had EGFRm+ (Del19/L858R) advanced NSCLC and acquired T790M after first-line afatinib. Pts completed afatinib and started osimertinib treatment ≥10 months before data entry to avoid early censoring and ensure mature data collection. Patient subgroups were defined based on baseline characteristics (eg, ECOG PS, age, ethnicity). The primary outcome was ToT from afatinib initiation to osimertinib discontinuation. Results: A total of 204 pts were included in the GioTag study: 15.2% had ECOG PS ≥2; 7.4% were aged ≥75 years; 8.8% were African-American. Pts generally considered to have a poor prognosis derived clinical benefit from the afatinib–osimertinib sequence: median ToT for pts with ECOG PS ≥2 (n=31) was 22.2 months (90%CI 16.0–27.0; vs pts with ECOG PS 0/1 [n=153; 31.3 months; 27.6–44.5] P<.001); and for pts aged ≥75 years (n=15), ToT was 19.9 months (9.7–not evaluable [NE]; vs pts aged <75 years [n=189; 28.1 months; 26.6–31.3] P=.382). In African-American pts, median ToT was 27.6 months (90%CI 24.7–NE). Of 180 pts with available data, 75.0% had no change or an improvement in ECOG PS from the start of afatinib to the start of osimertinib treatment; 24.4% of pts had a deterioration in ECOG PS by 1 step and 0.6% of pts had a deterioration by 2 steps. Conclusions: First-line afatinib followed by osimertinib is a feasible therapeutic strategy in pts with EGFRm+ NSCLC and acquired T790M, including those who are often under-represented in RCTs. Clinical benefit (measured by ToT) was seen among pts with poor prognosis (ECOG PS ≥2), pts aged ≥75 years, and African-American pts.

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First-line cisplatin (P) with docetaxel (TXT) or vinorelbine (VNR) in patients with advanced non-small cell lung cancer: A randomized phase II trial of the Gruppo Oncologico Italia Meridionale

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e19042 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e19042-e19042

Author(s):

V. Gebbia ◽

D. Galetta ◽

V. Lorusso ◽

M. Caruso ◽

F. Riccardi ◽

...

Keyword(s):

Advanced Nsclc ◽

Response Rate ◽

Phase Ii Trial ◽

Stage Iv ◽

Hematological Toxicity ◽

First Line ◽

Primary Endpoints ◽

Randomized Phase Ii ◽

P 75 ◽

Ecog Ps

e19042 Background: P-based doublets are considered standard therapy for advanced NSCLC. The GOIM consider P/VNR as a reference treatment. P/TXT doublet has been reported to be active but it's not well known its real impact on QoL in comparison to P/VNR. Methods: Pts received either 6 courses of P/TXT or P/VNR with QoL and safety being the primary endpoints. Secondary endpoint included response rate, TTP, OS, and tolerability. Patients with stage IV/IIIB, age ≤70, and ECOG PS 0–1, were eligible. Sample size was calculated according to Fleming's single-stage procedure. QoL was analysed using the EORTC questionnaire, responses and toxicity according to the RECIST and NCI-CTC criteria. Pts were randomized to: TXT 75 mg/m2 over 60 min followed by P 75 mg/m2 on d1 every 21 d, or VNR 30 mg/m2 on d 1,8 and P 80 mg/m2 on d1 every 21 d. Results: From 12/06 to 3/08 86 pts were enrolled: P/TXT 42pts, M/F 32/10, IIIB/IV 8/34, squamous/not-squamous:13/29, median age 61 (r 41–70); P/VNR 44 pts, M/F 35/9, IIIB/IV 10/33, squamous/not-squamous 14/30, median age 62 (r 44/70). No statistically significant differences were observed in QoL among the two arms. Detailed analysis of side-effects showed no difference among the two regimens with the exception of G3–4 neutropenia and leukopenia with were slightly higher in the P/VNR arm (p=0.02 and p=0.0005 respectively). The use of G- CSF/darbopoietin was more frequent in pts treated with P/VNR than in the P/TXT arm (p=0019). Conclusions: Final data show an equivalence among the two arms regarding QoL and activity but with a slightly more hematological toxicity in the P/VNR arm. Both regimens are to be considered as standards in the treated of advanced NSCLC. [Table: see text]

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OA04.02 CheckMate 817: First-Line Nivolumab + Ipilimumab in Patients with ECOG PS 2 and Other Special Populations with Advanced NSCLC

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2019.08.424 ◽

2019 ◽

Vol 14 (10) ◽

pp. S214-S215 ◽

Cited By ~ 11

Author(s):

F. Barlesi ◽

C. Audigier-Valette ◽

E. Felip ◽

T. Ciuleanu ◽

K. Jao ◽

...

Keyword(s):

Advanced Nsclc ◽

Special Populations ◽

First Line ◽

Ecog Ps

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Analysis of first-line treatment (tx) patterns in advanced non-small cell lung cancer (NSCLC) patients (pts) with compromised performance status (PS), organ dysfunction (dfxn) or other significant comorbidities.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21093 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21093-e21093

Author(s):

Julia Judd ◽

Elizabeth A. Handorf ◽

Brinda Gupta ◽

Martin Edelman

Keyword(s):

Kinase Inhibitors ◽

Advanced Nsclc ◽

Performance Status ◽

Single Agent ◽

The Elderly ◽

First Line ◽

Real World Data ◽

Vegf Inhibitors ◽

Chi Squared ◽

Ecog Ps

e21093 Background: NSCLC is a disease of the elderly and most cases are related to tobacco. Therefore, concomitant organ dfxn, which increases the risk of toxicity with cancer directed therapy, is prevalent. Patterns of care studies have shown that the elderly, those with organ dfxn or compromised PS are frequently not treated, despite prospective studies demonstrating survival benefit with active tx. We hypothesized that the advent of new, more active therapies has resulted in practice changes in these populations. Methods: We conducted a retrospective, observational cohort study using the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database to compare first line tx patterns from 2011 to 2020 in pts with advanced NSCLC meeting at least 1 of the following criteria: age > 70 years, organ dfxn (serum creatinine > 1.5 times the upper limit of normal [ULN] and/or total bilirubin > 2 times ULN), ECOG PS > 2 or documented HIV. Pts were excluded if there was a > 90-day post-diagnosis gap in EHR data. Tx patterns were categorized as having received standard, non-standard or no frontline tx. Tx groups included PD-1/PD-L1 inhibitor single agent, chemoimmunotherapy, platinum-based (Plat) doublet +/- VEGF inhibitors (VEGFi), single agent chemotherapy (chemo) and tyrosine kinase inhibitors (TKIs). Descriptive statistics were used to analyze tx patterns, and the relationship between txs and variables of interest were tested using Chi-squared tests or t-tests. Results: Of the 58,145 pts with advanced NSCLC in the database, 33,701 met at least 1 criterion for inclusion. There was a small but significant increase in the number of pts treated with standard therapy from 2011 to 2020 (p < 0.001). There was rapid uptake of PD-1/PD-L1 inhibitors as well as chemoimmunotherapy upon FDA approvals in 2016 and 2018, respectively. This correlated with a rapid decrease in the use of Plat-doublet chemo +/- VEGFi as well as a decrease in the number of pts receiving single agent chemo or not treated at all (Table). Conclusions: Real world data from 2011 to 2020 demonstrates an increase in the use of standard therapies as well as the rapid incorporation of immunotherapy into first line tx in advanced NSCLC pts who are elderly, have a poor PS, or organ dfxn. However, a substantial proportion of pts (28.9%) still do not receive any documented tx, within the Flatiron Health network.[Table: see text]

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Effect of first-line pembrolizumab treatment in individuals with advanced non-small cell lung cancer and poor performance status.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18796 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18796-e18796

Author(s):

Rajwanth Veluswamy ◽

Jiayi Ji ◽

Liangyuan Hu ◽

Xiaoliang Wang ◽

Cardinale B. Smith ◽

...

Keyword(s):

Treatment Group ◽

Real World ◽

Advanced Nsclc ◽

Performance Status ◽

Poor Performance ◽

Smoking History ◽

Poor Performance Status ◽

First Line ◽

Inverse Probability ◽

Ecog Ps

e18796 Background: There is limited evidence supporting the optimal use of immune checkpoint inhibitors (ICIs) in NSCLC patients with poor performance status (PS), as clinical trials exclude these patients. In this study, we use real-world oncology data to determine the impact of first line pembrolizumab vs. no treatment in high PD(L)-1 expressing cancers in individuals with advanced NSCLC and ECOG PS ≥2. Methods: We performed a retrospective cohort study of patients with advanced NSCLC with ECOG PS ≥2 between 09/01/2014 and 02/18/2020, using the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Patients were included if they were PD(L)-1 high (≥50%) and had clinical and treatment information recorded within 90 days of diagnosis. Real-world overall survival (rwOS) was defined as time from diagnosis to death (censored at last EHR activity). Median rwOS was estimated using weighted Kaplan-Meier methods. A marginal Cox structural model with inverse probability of treatment weighting was used to adjust for selection bias and estimate the effectiveness of pembrolizumab. The inverse probability weights were estimated using an ensemble machine learning technique, Super Learner, based on age, gender, race, practice type and smoking history. Adjusted hazard ratios (aHR) were estimated using weighted Cox proportional hazards models. Stratified analysis was conducted by ECOG PS (2 vs >2). Results: 217 (16%) individuals with advanced NSCLC and high PD(L)-1 expression received no treatment, compared to 546 (39%) individuals who received 1L pembrolizumab. The no-treatment group had a lower proportion of ECOG 2 compared to the pembrolizumab group (Table). Median rwOS in the no-treatment group was 2.4 months, compared to 7.1 months in the pembrolizumab group (p<0.001). In unadjusted survival analyses in the entire cohort and in cohorts stratified by ECOG status, treatment with pembrolizumab was associated with a significantly lower risk of death (hazard ratio [HR]: 0.38, 95% Confidence Interval [CI]: 0.31-0.45). In adjusted analyses, individuals treated with pembrolizumab had improved survival (HR: 0.40, 95% CI: 0.35-0.45). Conclusions: Our analysis of real-world clinical oncology data demonstrated that 1L treatment with pembrolizumab was associated with significantly improved rwOS among individuals with ECOG ≥ 2. [Table: see text]

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PD-(L)1 inhibitors as monotherapy for the first-line treatment of non-small cell lung cancer patients with high PD-L1 expression: A network meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9076 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9076-9076

Author(s):

Margarita Majem ◽

Manuel Cobo ◽

Dolores Isla ◽

Diego Marquez-Medina ◽

Delvys Rodriguez-Abreu ◽

...

Keyword(s):

Advanced Nsclc ◽

Meta Analysis ◽

Statistical Significance ◽

Stage Iv ◽

Small Cell ◽

Small Cell Lung ◽

First Line ◽

Former Smokers ◽

Ecog Ps ◽

Nsclc Patients

9076 Background: PD-L1 has emerged as a potential biomarker for predicting responses to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC). In this network meta-analysis, we aimed to evaluate the efficacy of first-line PD-(L)1 monotherapy in advanced NSCLC patients with high PD-L1 expression. Methods: We conducted a systematic search in PubMed to identify all eligible trials from inception until 1 November 2020, with no start date limit applied. Only phase III trials evaluating the efficacy of first-line (1L) PD-(L)1 monotherapy in patients with stage IIIB/stage IV NSCLC and high PD-L1 expression were included. Results: Six clinical trials (KEYNOTE-024, KEYNOTE-042, EMPOWER Lung-01, IMpower110, MYSTIC and CheckMate-026) with 2,111 patients were included. In head-to-head comparisons, immunotherapy showed a significant improvement in progression-free survival (PFS: HRpooled = 0.69, 95% CI: 0.52-0.90, p = 0.007), overall survival (OS: HRpooled = 0.69, 95% CI: 0.61-0.78; p < 0.001) and overall response rate (ORR) (Risk ratio [RR]pooled = 1.354, 95% CI: 1.04-1.762, p = 0.024) compared to chemotherapy (CT). In the assessment of relative efficacy for PFS through indirect comparisons, pembrolizumab (results from KEYNOTE-024) ranked highest followed by cemiplimab and atezolizumab, with statistical significance determined across some of the drugs. In terms of OS, cemiplimab ranked highest followed by atezolizumab and pembrolizumab, although non-significant OS was determined across these drugs. Overall, 1L PD-(L)1 monotherapy improved OS in almost all subgroups, reaching statistical significance in men (HRpooled = 0.624, 95% CI: 0.51-0.72, p < 0.001), non-Asian patients (HRpooled = 0.66, 95% CI: 0.55-0.79, p < 0.001), all patients regardless of age ( < 65 years [HRpooled = 0.72, 95% CI: 0.57-0.90, p = 0.005]; ≥65 years [HRpooled = 0.61, 95% CI: 0.48-0.77, p < 0.001]), ECOG PS status (ECOG PS = 0 [HRpooled = 0.68, 95% CI: 0.56-0.82, p < 0.001; ECOG PS = 1 [HRpooled = 0.59, 95% CI: 0.43-0.82, p = 0.001) and histological tumour type (Squamous [HRpooled = 0.49, 95% CI: 0.37-0.67, p < 0.001; Non-squamous [HRpooled = 0.67, 95% CI: 0.52-0.87, p = 0.003). In the case of smokers and NSCLC stage, only current/former smokers (HRpooled = 0.623, 95% CI: 0.47-0.83, p = 0.001) and patients with stage IV disease* (HRpooled = 0.687, 95% CI: 0.59-0.81, p < 0.001) benefited from single PD-(L)1 monotherapy over CT. Conclusions: PD-(L)1 inhibitor monotherapy improves efficacy outcomes in the 1L setting of advanced NSCLC patients with high PD-L1 expression. Current/former smokers ≥65 years, with ECOG PS = 1 and squamous NSCLC benefited most from this therapy. *KEYNOTE-042 was the only study including patients with stage IIIB NSCLC.

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