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Ali Mirmiran, Albert Dekker Commented on a Post
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Highlights from Gather Session: EGFR-positive Metastatic Non-Small Cell Lung Cancer 

NSCLC Connect recently hosted a Q&A session with Oncologists regarding EGFR-positive Metastatic Non-Small Cell Lung Cancer (mNSCLC)

Below are some highlights from the discussion:

Some respondents noted that clinical trial data (such as from the recent RELAY study) showed the combined use of ramucirumab plus erlotinib was useful in some patient populations; however, various oncologists said they wouldn’t change from their current choice of treatment due to factors of cost and convenience.

  • “The data that came from the RELAY study, which was a Phase 3 study using this combination ramucirumab plus erlotinib versus erlotinib plus placebo, was very, very good and were described in the RELAY study. This study basically showed impressive progression-free survival and basically matched the exon 19 deletion, which is the most sensitive EGFR mutation that we have identified so far.”
  • “The data is very impressive in patients with EGFR mutation due to dual blockage. In patients who have EGFR mutation, I definitely would treat them combining VEGF inhibitor for improvement in progression-free survival. It is not going to be used in all patients but subgroup of patients who have good performance status and EGFR mutated would be the patient I will use.”
  • “Clinical data is very important as a basis of how I make my decisions when I decide to pick a combination to treat and having a PFS in first line similar to osimertinib for this combination at 19 months, PFS is impressive. I've been still picking single-agent osimertinib over this combination just for more convenience for patients.”
  • “I realize that the data is competitive in terms of prognostic outcomes, progression-free survival, and maybe even overall survival, but the cost of using Tagrisso is less than the cost of using combination of ramucirumab with erlotinib, which is a far more expensive program of treatment.”

Regarding their thoughts on the treatment options currently available for patients with EGFR mutations – specifically EGFR exon 21, several respondents expressed other preferences, but were open to trying erlotinib and ramucirumab based on emerging data.

One respondent noted the need for second- or third-line options for their mNSCLC patients.

  • “I think patients have excellent available treatment options for first line, be it osimertinib or combination of erlotinib with ramucirumab. I think the biggest unmet need for those patients after they progress on first line, what to do next, so we tend to move to chemotherapy or chemotherapy and immune therapy, but it goes quickly downhill. We don't have good second- or third-line targeted options like we do have in ALK-positive lung cancer, and I wish we had more targeted therapy in that setting, especially newer-generation TKIs.”

For discussions with patients regarding choice of treatment, most respondents offered support, with conversation often focusing on quality of life, survival, etc.

  • “I explain to them this is palliative and the goal is to keep their disease in check as much as possible to minimize side effects or complications of the disease. We discuss quality of life. We tell them that we could start therapy and watch for side effects. And if they're not tolerating, or if we can get their side effects under control, we would recommend transitioning to best supportive care or hospice.”

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  • January 11, 2023
    Interesting data on combination Cyramza....
  • August 20, 2022
    I used this for a few patients over last 2-3 years. Definitely more side effects such as rash and diarrhea. I have used this only for highly educated patients who Show More
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A clinical nomogram based on absolute count of lymphocyte subsets for predicting overall survival in patients with non-small cell lung cancer

The higher the absolute count of lymphocyte subsets, the longer the overall survival of the NSCLC patients. * The nomogram constructed by the absolute count of lymphocyte subsets can accurately ..... see more

Source : https://www.sciencedirect.com/science/article/pii/S156757692200875X?via=ihub

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Conclusions: " We established a prognostic nomogram to predict OS of the NSCLC patient. This nomogram provided a more quantitative, scientific and objective basis for accurate diagnosis and individual management of NSCLC patients."


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  • December 30, 2022
    someone would assume that now on patients on clinical trials will need to be radimized based on this nomogram. It would be interesting to see NCCN opinion in this regards Show More
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Moving Immune Checkpoint Inhibitors to Early Non-Small Cell Lung Cancer: A Narrative Review - PubMed

Lung cancer is the leading cause of cancer-related death worldwide. Since prognosis of early-stage non-small cell lung cancer (NSCLC) remains dismal for common relapses after curative surgery, considerable efforts are ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/36497292/


Conclusions: Unanswered questions in perioperative therapy in NSCLC include the optimal sequence and timing of chemotherapy and immunotherapy, the potential of combination strategies, the role of predictive biomarkers for patient selection and the choice of useful endpoints in clinical investigation.


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  • December 30, 2022
    6-18 months and this all will be well established
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Prognostic role of modified Glasgow Prognostic score in elderly non-small cell lung cancer patients treated with anti-PD-1 antibodies

Available online 29 November 2022 Author links open overlay panel Tomohiro Tanaka a Person b Envelope Show more This study aimed to investigate whether the immunosenescence-related score is a critical ..... see more

Source : https://www.sciencedirect.com/science/article/abs/pii/S2212534522001447?via=ihub



Conclusions: High mGPS scores significantly impaired DCR, mPFS, and mOS in patients with advanced NSCLC treated with anti-PD-1 antibodies.

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A Randomized Phase 2 Trial of Nivolumab Versus Nivolumab-Ipilimumab Combination in EGFR-Mutant NSCLC

Although immune checkpoint inhibitors (ICIs) have dramatically improved outcomes for nononcogene-addicted NSCLC, monotherapy with programmed cell death protein-1 (PD1) inhibition has been associated with low efficacy in the EGFR-mutant setting. ..... see more

Source : https://www.jtocrr.org/article/S2666-3643(22)00140-0/fulltext



Conclusions: Immune checkpoint inhibition is ineffective in EGFR TKI–resistant NSCLC. Whereas a small subgroup of EGFR-mutant NSCLC may be immunogenic and responsive to ICI, better biomarkers are needed to select appropriate patients."

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  • December 15, 2022
    In my opinion it is extremely important as it proves another proof that both AO and IO combos have no activity in this disease
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A Subset of VEGFR-TKIs Activates AMPK in LKB1-mutant Lung Cancer - PubMed

The mutation of tumor suppressor gene liver kinase B1 (LKB1) has a prevalence of about 20% in non-small cell lung cancer (NSCLC). LKB1-mutant lung cancer is characterized by enhanced aggressiveness ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/36459496/


Conclusions: This study discovered AMPK as an important off-target of apatinib, and elucidated different effects of this cluster of VEGFR-TKIs on AMPK. This finding can be the basis for the accurate and combined application of these drugs in clinic, and highlights the subset of VEGFR-TKIs including apatinib and anlotinib are potentially...

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Phase I Study Evaluating Glesatinib (MGCD265), An Inhibitor of MET and AXL, in Patients with Non-small Cell Lung Cancer and Other Advanced Solid Tumors - Targeted Oncology

Background Heightened signaling by mesenchymal epithelial transition factor (MET) is implicated in tumorigenesis. Glesatinib is an investigational, oral inhibitor of MET and AXL. Objective This phase I study determined the ..... see more

Source : https://link.springer.com/article/10.1007/s11523-022-00931-9


Conclusions: The safety profile of single-agent glesatinib was acceptable. SDD 750 mg twice daily was selected as the preferred glesatinib formulation and dose based on clinical activity, safety, and PK data. Observations from this study led to initiation of a phase II study of glesatinib in patients with NSCLC stratified by type of MET...

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Efficacy of immune checkpoint inhibitors in non-small cell lung cancer with uncommon histology: a propensity-score-matched analysis - PubMed

doi: 10.1186/s12890-021-01681-6. 1 Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan. 2 Second Division, Department of Internal Medicine, Hamamatsu University School of ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/34600514/


Conclusions: ICIs had similar clinical efficacy for treatment of uNSCLC and cNSCLC. Good ECOG-PS and PD-L1 expression were predictive for efficacy of ICIs in uNSCLC.

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  • December 03, 2022
    It was suspected to be the case but nice to know
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RNA Structural Dynamics Modulate EGFR-TKI Resistance Through Controlling YRDC Translation in NSCLC Cells

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) positively affect the initial control ratio of non-small cell lung cancer (NSC... see more

Source : https://www.sciencedirect.com/science/article/pii/S1672022922001425?via=ihub

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Conclusions: Conclusions/Relevance: Our study reveals an unprecedented mechanism through which the RNA structure switch modulates EGFR-TKI resistance by controlling YRDC mRNA translation in an ELAVL1-dependent manner.

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  • December 03, 2022
    I am lost a bit; so RNA is able to b self regulated on mRNA level?
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Ongoing progress in BRAF-mutated non-small cell lung cancer - PubMed

Activating BRAF mutations are detected in 1.5% to 4.5% of patients with non-small cell lung cancer (NSCLC). These mutations involve the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway, and affect proliferation, ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/36331404/


Relevance: First-generation BRAF inhibitors are not active in the class II and III BRAF mutations that form the other half of BRAF mutations in NSCLC. New RAF inhibitors are being investigated in early trials. Novel treatment combinations, particularly with immune checkpoint inhibitors, are also underway. Patient referral to expert centers and...

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  • November 25, 2022
    obviously with Braf inhibitors it would be better
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Comparison of 22C3-PD-L1 Expression Between Paired Tumor... : Applied Immunohistochemistry & Molecular Morphology

ion. A total of 460 paired paraffin blocks of surgical NSCLC specimens were analyzed using the 22C3-PD-L1 assay. PD-L1 expression between 2 paired paraffin blocks was calculated using 3 classification ..... see more

Source : https://journals.lww.com/appliedimmunohist/Fulltext/9900/Comparison_of_22C3_PD_L1_Expression_Between_Paired.60.aspx


Conclusions: In cases that harbored different morphology in different paraffin blocks, the dual-block immunohistochemistry assessment method is recommended due to the intratumoral heterogeneity.


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  • November 25, 2022
    We know that tumors are heterogeneous but in real life how many blocks will you test
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BIR Publications

Therapy and prognosis of several solid and hematologic malignancies, including non-small cell lung cancer (NSCLC), have been favourably impacted by the introduction of immune checkpoint inhibitors (ICIs). Their mechanism of ..... see more

Source : https://www.birpublications.org/doi/10.1259/bjr.20210270


Conclusions: We will explore the role of radiomics in the setting of ICI-treated patients.


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Multiplexed imaging of tumor immune microenvironmental markers in locally advanced or metastatic non-small-cell lung cancer characterizes the features of response to PD-1 blockade plus chemotherapy - PubMed

Tumor immune microenvironmental marker expression, especially CD8/PD-L1 or CD68/PD-L1 co-expression, was associated with the efficacy of PD-1 blockade plus chemotherapy as first-line treatment in patients with advanced NSCLC. see more

Source : https://pubmed.ncbi.nlm.nih.gov/36331328/


Summary: Multiplexed imaging of tumor immune microenvironmental markers in locally advanced or metastatic non-small-cell lung cancer characterizes the features of response to PD-1 blockade plus chemotherapy

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The impact of patient travel time on disparities in treatment for early stage lung cancer in California

Background Travel time to treatment facilities may impede the receipt of guideline-concordant treatment (GCT) among patients diagnosed with early-stage non-small cell lung cancer (ES-NSCLC). We investigated the relative contribution of ..... see more

Source : https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0272076


Conclusion: The benefit of GCT observed with increased travel times may be a ‘Travel Time Paradox,’ and may vary across racial/ethnic and socioeconomic groups.

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  • November 06, 2022
    obviously the further people live the harder is to get
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Genomic landscape of lung cancer in the young

BackgroundLung cancer in the young is a rare entity of great interest due to the high frequency of targetable mutations. In this study, we explored the genomic landscape of non-small ..... see more

Source : https://www.frontiersin.org/articles/10.3389/fonc.2022.910117/full


Conclusion: NSCLC in the young in our cohort was characterized by a high frequency of actionable genetic aberrations and a low TMB, which was also true for our older patients. The enrichment of actionable mutations in young patients described in other reports might be attributed to differences in the etiology and clinicopathological...

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  • November 06, 2022
    it makes sense; younger patients have driver mutations
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Developing an effective quality evaluation strategy of next-generation sequencing for accurate detecting non-small cell lung cancer samples with variable characteristics: a real-world clinical practice - Journal of Cancer Research and Clinical Oncology

Purpose Next-generation sequencing (NGS) has been widely used in determining molecular profiling of non-small cell lung cancer (NSCLC). However, low-quality sequencing data may be generated with formalin-fixed and paraffin-embedded (FFPE) ..... see more

Source : https://link.springer.com/article/10.1007/s00432-022-04388-1


Conclusions: Our study demonstrates that the real-world clinical adoption of an effective QC strategy for NGS is necessary to ensure accurate results from FFPE samples of NSCLC with variable characteristics. Validation of actionable alterations by additional methods is highly recommended in cases with low QC score, particularly for the...

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  • November 06, 2022
    biggest question who to put all those mutations together
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Knockdown of growth differentiation factor-15 inhibited nonsmall cell lung cancer through inactivating PTEN/PI3K/AKT signaling pathway - Genes & Genomics

Background Non-small cell lung cancer (NSCLC) is characterized by high morbidity and mortality in the world. Growth and differentiation factor 15 (GDF15) has been proved to play an important role ..... see more

Source : https://link.springer.com/article/10.1007/s13258-022-01328-8


Conclusions: GDF15 plays an important role in NSCLC progression. GDF15 mediated PTEN/PI3K/AKT signaling pathway might be the potential therapeutic targets for the prevention and treatment of GDF15.


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Immunochemotherapy includes pembrolizumab for stage IIIB lung squamous cell carcinoma: a case report

Lung cancer is a malignant tumor with high morbidity and mortality ( 1, 2). Conventional treatment methods include surgical treatment, chemotherapy, radiotherapy, and targeted therapy ( 3- 5). With the ..... see more

Source : https://atm.amegroups.com/article/view/102133/html


Conclusions: This case reminds us that the induction treatment pattern of pembrolizumab combined with chemotherapy for subsequent conversion surgery can be a potentially curative treatment option for locally advanced stage IIIB patients. The monitoring of thyroid-related indicators is important during immunotherapy, especially in the first...

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TECPR1 Induces Apoptosis in Non-Small Cell Lung Carcinoma via ATG5 Upregulation-Induced Autophagy Promotion - PubMed

1 Department of Pulmonary and Critical Care Medicine, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. 2 Department of Pulmonary and Critical Care ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/36197771/


Conclusion: TECPR1 induces NSCLC cell apoptosis via ATG5 upregulation-induced autophagy promotion.

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Conclusions: High level of baseline MTV corresponded to shorter PFS and OS, especially when the cut-off value was set between 50-100 cm3. MTV is a potential predictive value for the outcome of ICIs in NSCLC patients.

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  • October 09, 2022
    makes sense to some degree. It was well known with traditional chemotherapy.