CLO19-033: Afatinib Followed by Osimertinib in EGFR Mutation-Positive (EGFRm+) Advanced NSCLC: Subgroup Analyses of the GioTag Study by ECOG PS, Age, and Ethnicity

2019 ◽  
Vol 17 (3.5) ◽  
pp. CLO19-033
Author(s):  
Balazs Halmos ◽  
Maximilian J. Hochmair ◽  
Alessandro Morabito ◽  
Desiree Hao ◽  
Cheng-Ta Yang ◽  
...  
Keyword(s):  
African American ◽  
Clinical Benefit ◽  
Poor Prognosis ◽  
Advanced Nsclc ◽  
Acquired Resistance ◽  
Subsequent Treatment ◽  
First Line ◽  
Subgroup Analyses ◽  
Ecog Ps ◽  
The Impact

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.

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

2021 ◽  
Vol 16 (10) ◽  
pp. S948-S949
Author(s):  
B. Ricciuti ◽  
J. Alessi ◽  
S. Alden ◽  
G. Recondo ◽  
M. Nishino ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Advanced Nsclc ◽  
First Line ◽  
Ecog Ps ◽  
Very High

Patterns and management of progression on first-line ipilimumab combined with anti-PD-1 (IPI+PD1) in metastatic melanoma (MM) patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9533-9533
Author(s):  
Ines Pires Da Silva ◽  
Judith M. Versluis ◽  
Tasnia Ahmed ◽  
Douglas Buckner Johnson ◽  
Jennifer Soon ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Acquired Resistance ◽  
Progression Free Survival ◽  
Initial Response ◽  
Best Supportive Care ◽  
First Line ◽  
Disease Characteristics ◽  
Best Response ◽  
Investigational Drugs ◽  
Ecog Ps

9533 Background: First line IPI+PD1 induces long-term response in 36% of MM patients (pts); however, the majority of pts will progress and may require further treatment, which is yet to be established. We studied the patterns of progressive disease (PD) on 1st line IPI+PD1, and the management and outcomes in MM pts. Methods: Demographics, disease characteristics, nature of PD, subsequent treatments and outcomes were examined in MM pts with PD on 1st line IPI+PD1. Multivariable analyses (MVA) identified factors associated with patterns of PD: innate resistance (IR) = PD as best response or stable disease (SD) < 6 mo; acquired resistance (AR) = PD after initial response or SD ≥ 6 mo. Results: 310 MM pts from 14 melanoma centres were included; 208 (67%) had PD during and 102 (33%) after ceasing IPI+PD1. Overall med. progression-free survival (mPFS) was 2.8 mo (CI 95% 2.7 – 3.0); 187 pts (60%) had IR (mPFS 2.2 [2.1 – 2.5]), 112 pts (36%) had AR (mPFS 8.5 [7.2 – 10.2]) and 11 pts (4%) had pseudoprogression, i.e. PD followed by response without changing treatment (mPFS 2.7 mo [1.4 – NA]). On MVA, pts with ECOG PS ≥ 1 were more likely to have IR vs AR; and within IR pts, those with head & neck primary melanomas and lung metastases were more likely to have PD < 1.5 mo. Most pts with IR (68%) had PD in multiple sites, while 61% AR pts had PD in a single site. Brain was most common site of single organ PD; 49% of IR and 41% of AR. Med. follow-up from PD was 32.7 mo (28.1 – 36.8). After PD, 61 pts (20%) had best supportive care (26% of IR and 11% of AR pts). 259 pts (80%) received further treatment: 39% IR pts had systemic treatment (ST) only and 27% had ST + local; 31% AR pts had ST only and 39% had ST + local. Of 200 pts (65%) who had ST(+/-local), 54% had 1 line of ST and 46% had ≥ 2; 1st line ST (ST1) was BRAF/MEKi in 36% of pts, PD1 in 32%, IPI+PD1 in 7%, investigational drugs in 11%, chemotherapy in 9% and others in 5%. ORR in IR pts was lower than in AR pts for every type of ST1 (see Table). Med. OS from PD was 11.4 mo (CI 95% 9.6 – 16.1); IR 6.4 mo (CI 95% 5.6 – 10.2) and AR 26.1 mo (CI 95% 17.1 – NA). Conclusions: These data suggest longer OS from PD for AR vs IR pts independent of ST type. BRAF/MEKi, rechallenge with PD1+/-IPI and investigational drugs showed activity after PD on IPI+PD1, while chemotherapy has no role in this context.[Table: see text]

Capecitabine plus oxaliplatin (XELOX) followed by capecitabine plus irinotecan (XELIRI) in a sequential schedule in first-line metastatic colorectal cancer (MCRC): a phase II multicenter study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13516-13516
Author(s):  
J. Cassinello ◽  
J. V. Álvarez ◽  
M. J. García-López ◽  
E. Pujol ◽  
A. Colmenarejo ◽  
...  
Keyword(s):  
Phase Ii ◽  
Dose Intensity ◽  
Hepatic Function ◽  
Phase Ii Trials ◽  
First Line ◽  
Highly Active ◽  
Sequential Schedule ◽  
Ecog Ps ◽  
The Impact

13516 Background: In phase II trials, XELOX and XELIRI were highly active and well tolerated in first-line MCRC. The aim of this study is to explore the efficacy and safety of XELOX followed by XELIRI as first-line treatment in MCRC. Specifically, we wanted to evaluate the impact of sequential scheduling on the dose-limiting neurotoxicity associated with oxaliplatin accumulation. Methods: Eligible patients (pts) had histologically or cytologically confirmed MCRC, ECOG PS ≤ 2 and adequate bone marrow, renal and hepatic function. Prior chemotherapy for MCRC was not allowed. Pts received 4 cycles of XELOX (capecitabine 1000mg/m2 orally bid d1–14 + oxaliplatin 130mg/m2 i.v. d1, q3w) followed by 4 cycles of XELIRI (capecitabine 1000mg/m2 bid d1–14 + irinotecan 240mg/m2 i.v. d1, q3w). This sequential schedule was repeated until unacceptable toxicity or disease progression. Results: Of the 35 pts analized to date: M/F (69%/31%); median age 68 years (range 41–78); ECOG PS 0–1 (94%); surgery (77%) and adjuvant chemotherapy (31%). 240 cycles (median 6, range 1–16) have been administered. 35 pts received XELOX (123 cycles, median 4), and 21 pts received XELIRI (83 cycles, median 4) in the first sequential schedule. In the second sequential schedule 6 pts received XELOX (22 cycles, median 4) and 4 pts received XELIRI (12 cycles, median 3.5). Median relative dose intensity was 88% for XEL, 96% for OX and 92% for IRI. In 27 efficacy evaluable pts, the ORR was 48% (95% CI, 29–67%). Eight pts were not evaluable due to adverse events (n=6), ongoing treatment (n=1) and lost of follow up (n=1). Conclusions: This sequential schedule is active and well tolerated in first-line MCRC. The improvement/recovery of the oxaliplatin-related neurotoxicity during the XELIRI phase is also promising and allows the re-treatment with oxapliplatin in the next sequence without accumulating neurotoxicity. Final results will be presented at the meeting. [Table: see text] No significant financial relationships to disclose.

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

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]

scholarly journals Cost-Effectiveness Analysis of Nivolumab Plus Ipilimumab for Advanced Non-Small-Cell Lung Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaomin Wan ◽  
Xiaohui Zeng ◽  
Liubao Peng ◽  
Ye Peng ◽  
Qiao Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cost Effectiveness ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Subgroup Analyses ◽  
The Cost

Objective: This study evaluated the cost-effectiveness of nivolumab plus ipilimumab vs. chemotherapy in the first-line setting for patients with advanced non-small-cell lung cancer (NSCLC) from the US payer perspective.Materials and methods: A Markov model wasdeveloped to evaluate the cost and effectiveness of nivolumab plus ipilimumab vs. chemotherapy in the first-line treatment of advanced NSCLC. The survival benefits of nivolumab plus ipilimumab were based on the results of the CheckMate 227 trial. The main endpoints of the model were cost, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER). Univariable and probabilistic sensitivity analyses were conducted to assess model uncertainty. Additonal subgroup analyses were also performed.Results: nivolumab plus ipilimumab produced a gain of 0.62 QALYs, at a cost of $104238 per QALY. The variables that had the greatest influence on the ICER were body weight and overall survival (OS) hazard ratio (HR). The probability of nivolumab plus ipilimumab being cost-effectiveness compared to chemotherapy is 50.7 and 66.2% when the willingness-to-pay (WTP) value is $ 100,000 and $ 150,000 per QALY. The results of subgroup analyses showed the ICER remained below $150,000/QALY regardless of the PD-L1 expression level.Conclusions: nivolumab plus ipilimumab was estimated to be cost-effective compared with chemotherapy for patients with advanced NSCLC at a WTP threshold from 100,000/QALY to 150,000/QALY.

scholarly journals LKB1 mutations are not associated with the efficacy of first-line and second-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC): a post hoc analysis of the TAILOR trial

ESMO Open ◽  
2020 ◽  
Vol 5 (3) ◽  
pp. e000748
Author(s):  
Claudio Vernieri ◽  
Monica Ganzinelli ◽  
Eliana Rulli ◽  
Gabriella Farina ◽  
Anna Cecilia Bettini ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Cytotoxic Chemotherapy ◽  
Second Line ◽  
Small Cell Lung ◽  
First Line ◽  
Mutational Status ◽  
Platinum Based Chemotherapy ◽  
Nsclc Patients ◽  
The Impact ◽  
Chemotherapy Efficacy

PurposeIn patients with advanced lung adenocarcinoma, the impact of LKB1 mutations on cytotoxic chemotherapy efficacy remains poorly explored. Here, we aimed at investigating the potential impact of LKB1 mutational status on chemotherapy efficacy in advanced non-small-cell lung cancer (NSCLC) patients enrolled in the TArceva Italian Lung Optimisation tRial (TAILOR) trial.MethodsThe multicenter TAILOR trial randomised patients with EGFR-wild type (wt) advanced NSCLC progressing on/after previous platinum-based chemotherapy to receive docetaxel or erlotinib. Here, we evaluated the impact of LKB1 mutational status on progression-free survival (PFS) and overall survival (OS) in patients treated with second-line docetaxel/erlotinib or during prior platinum-based chemotherapy.ResultsOut of 222 patients randomised in the TAILOR trial, left-over tumour tissues were available for 188 patients, and 120 patients with evaluable LKB1 status were included. Of them, 17 (14.17%) patients had LKB1-mutated tumours, while 103 (85.83%) had LKB1-wt disease. During second-line treatment, PFS and OS were not statistically significantly different in patients with LKB1-mutated when compared with LKB1-wt NSCLC (adjusted HR (aHR)=1.29, 95% CI 0.75 to 2.21; p=0.364 and aHR=1.41, 95% CI 0.82 to 2.44; p=0.218, respectively). Similarly, we found no significant association between LKB1 mutations and patient PFS or OS during prior first-line platinum-based chemotherapy (aHR=1.04, 95% CI 0.55 to 1.97; p=0.910 and aHR=0.83, 95% CI 0.42 to 1.65; p=0.602, respectively).ConclusionAmong advanced NSCLC patients receiving two lines of systemic therapy, LKB1 mutations were not associated with PFS or OS during second-line docetaxel or prior first-line platinum-based chemotherapy. While larger prospective trials are needed to confirm our findings, cytotoxic chemotherapy remains the backbone of investigational combination strategies in this patient population.

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

2019 ◽  
Vol 14 (10) ◽  
pp. S214-S215 ◽  
Author(s):  
F. Barlesi ◽  
C. Audigier-Valette ◽  
E. Felip ◽  
T. Ciuleanu ◽  
K. Jao ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Special Populations ◽  
First Line ◽  
Ecog Ps

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.

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]

Impact of Subsequent Therapies on Outcome of the FIRE-3/AIO KRK0306 Trial: First-Line Therapy With FOLFIRI Plus Cetuximab or Bevacizumab in Patients With KRAS Wild-Type Tumors in Metastatic Colorectal Cancer

2015 ◽  
Vol 33 (32) ◽  
pp. 3718-3726 ◽  
Author(s):  
Dominik P. Modest ◽  
Sebastian Stintzing ◽  
Ludwig Fischer von Weikersthal ◽  
Thomas Decker ◽  
Alexander Kiani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Subsequent Treatment ◽  
Hazard Ratio ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
The Impact

Purpose We investigated choice and efficacy of subsequent treatment, with special focus on second-line therapy, in the FIRE-3 trial (FOLFIRI plus cetuximab [arm A] or bevacizumab [arm B]) for patients with KRAS wild-type metastatic colorectal cancer. Patients and Methods Start of subsequent-line (second or third) therapy was defined as use of an antitumor drug that was not part of the previous regimen. We evaluated choice, duration, and efficacy of subsequent therapy and determined the impact of subsequent-line treatment on outcome of patients in FIRE-3. Results Of 592 patients in the intent-to-treat population, 414 (69.9%) received second-line and 256 (43.2%) received third-line therapy. In subsequent treatment lines, 47.1% of patients originally assigned to arm A received bevacizumab, and 52.2% originally assigned to arm B received either cetuximab or panitumumab. Oxaliplatin was subsequently used in 55.9% (arm A) and 53.2% (arm B) of patients. Second-line therapy was administered for a median duration of 5.0 versus 3.2 months (P < .001) in study arm A versus B. Progression-free (6.5 v 4.7 months; hazard ratio, 0.68; 95% CI, 0.54 to 0.85; P < .001) and overall survival (16.3 v 13.2 months; hazard ratio, 0.70; 95% CI, 0.55 to 0.88; P = .0021) from start of second-line therapy were longer in patients in arm A compared with arm B. Conclusion Our data suggest that the sequence of drug application might be more important than exposure to single agents. In patients with RAS wild-type tumors, first-line application of anti–epidermal growth factor receptor–directed therapy may represent a favorable condition for promoting effective subsequent therapy including antiangiogenic agents.

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