Choiralston3083

G724S has been described to mediate resistance to first- and third-generation EGFR tyrosine kinase inhibitors (TKIs). Invitro experiments have provided compelling evidence that G724S retains sensitivity for afatinib. Nevertheless, limited data have reported the clinical efficacy of afatinib in patients with NSCLC harboring G724S mutation.

We identified 52 patients with NSCLC with

G724S from an inhouse database and comprehensively profiled their concurrent mutation statuses. Treatments and clinical outcomes were also collected.

Of 52 G724S-positive patients, 39 harbored concomitant

exon 19 deletion (19del), and all 37 of the 39 patients who had available clinical data were detected with a G724S mutation after receiving EGFR TKIs. A rare variant of 19del E746_S752delinsV co-occurred with G724S the most frequently (n= 29), whereas 7 of 10 patients with concomitant

exon 20 mutation were TKI treatment naive. S768I was the most common mutation in exon 20 (n= 7). One patient harbored a concomitant

a resistant mutation against EGFR TKI preferentially in the context of a rare variant of 19del, whereas it might mediate differential mechanisms in the context of exon 20 mutation. We also found that afatinib could be a potential therapeutic option for patients with NSCLC with G724S.

EGFR G724S emerges as a resistant mutation against EGFR TKI preferentially in the context of a rare variant of 19del, whereas it might mediate differential mechanisms in the context of exon 20 mutation. We also found that afatinib could be a potential therapeutic option for patients with NSCLC with G724S.

Although treatment with osimertinib confers survival benefits in patients with lung cancer with the

T790M mutation, the mechanism of acquired resistance to osimertinib remains poorly understood. We conducted a prospective observational study to identify the mechanism on the basis of repeated tissue biopsies.

Patients with

-mutated advanced lung cancer with a T790M mutation detected on a tissue biopsy underwent a rebiopsy after developing acquired resistance to osimertinib. Nucleic acids extracted from the biopsy samples were subjected to targeted resequencing (Oncomine Comprehensive Assay), and circulating cell-free DNA (ccfDNA) was analyzed by CAncer Personalized Profiling by deep Sequencing (AVENIO ctDNA Surveillance Kit).

Between November 2016 and March 2020, a total of 87 patients were screened. Among them, 44 developed acquired resistance. Of these, 19 samples from rebiopsies and 12 from preosimertinib biopsies were able to be analyzed by an Oncomine Comprehensive Assay. A ccfDNA analysis was performed in 16 patients. Regarding the mechanisms of acquired resistance, structural change in EGFR, namely, C797S, G796S, or L792V, was the most frequent alteration, being observed in 57.9% of the cases.

gain was observed in 31.6% of the cases, and gains in cell cycle genes were observed in 26.3% of the cases. In addition, we identified

gain and an

mutation in a patient with small-cell transformation and a

V600E mutation in a patient with oligoprogressive disease.

A repeated tissue biopsy and a ccfDNA analysis were useful in analyzing the mechanisms underlying acquired resistance. A long treatment history of EGFR TKIs may result in a high percentage of EGFR structural change.

A repeated tissue biopsy and a ccfDNA analysis were useful in analyzing the mechanisms underlying acquired resistance. A long treatment history of EGFR TKIs may result in a high percentage of EGFR structural change.

fusions are oncogenic drivers in 1% to 3% of NSCLCs. The activity of immune checkpoint inhibitor (ICI)monotherapy or in combination with chemotherapy (chemotherapy with ICI [chemo-ICI]) in these tumors and their immunophenotype have not been systematically described.

In this multi-institutional retrospective study, tumor programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB) were evaluated in patients with

rearranged NSCLC. Time-to-treatment discontinuation (TTD) and objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) were calculated for patients treated with ICI or chemo-ICI in the metastatic setting.

A total of 184 patients were identified. Among 146 assessable cases, PD-L1 expression was less than 1% in 60 (41%), 1% to 49% in 35 (24%), and greater than or equal to 50% in 51 tumors (35%). Of 100 (92%) TMB-assessable tumors, 92 had less than 10 mutations per megabase. TMBwas significantly lower for

rearranged tumors (n= 97) compactivity.

It has been well established that

Thr790Met is one of the major resistance mechanisms to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). Nevertheless, whether

Thr790Leu (T790L), which shares the mutation site of Thr790 with

Thr790Met, mediates resistance to EGFR TKIs remains elusive. The treatment options for patients harboring this rare mutation have not been reported.

Capture-based targeted ultradeep sequencing was performed on tumor and plasma samples collected at various treatment milestones from three patients with advanced lung adenocarcinoma undergoing targeted therapy.

Needle biopsy of lymph node metastasis from patient 1 revealed

T790L at disease progression on first-line treatment of gefitinib. Patient 2 had

T790L identified from needle biopsy of lung tissue at disease progression on icotinib treatment. This patient was subsequently treated with osimertinib and achieved stable disease with a progression-free survival of 9 months. For patient 3, at disease recurrence after surgery, resected lung tumor tissue was retrieved for molecular profiling and revealed

exon 19 deletion and

T790L. The patient subsequently received osimertinib treatment and continued to benefit for 16 months and counting. She has maintained stable disease at the time of submission of this manuscript.

We revealed for the first time that

T790L may serve as a potential resistance mechanism to first-generation EGFR TKIs. We also report the first clinical evidence of efficacy generated by osimertinib in patients with lung adenocarcinoma harboring primary or acquired

T790L, shedding light on treatment options for this subset of patients.

We revealed for the first time that EGFR T790L may serve as a potential resistance mechanism to first-generation EGFR TKIs. We also report the first clinical evidence of efficacy generated by osimertinib in patients with lung adenocarcinoma harboring primary or acquired EGFR T790L, shedding light on treatment options for this subset of patients.

In patients with relapsed SCLC, amrubicin (AMR) is the current standard treatment in Japan. Nevertheless, its efficacy is not satisfactory and prognosis is poor. Preclinical study suggested that anthracycline agent might induce immunogenic cell death and work synergistically with immune checkpoint inhibitors.

Patients with relapsed SCLC who relapsed after completion of platinum-containing regimen were registered. Patients were treated with pembrolizumab (200 mg, flat dose on d 1, every 3 wk for 2 y) plus AMR (40 mg/m

on d 1-3, every 3 wk until progression). Primary end point was overall response rate (ORR). Secondary end points consisted of progression-free survival (PFS), overall survival, and safety. On the basis of the hypothesis that this treatment will improve ORR from 20% to 40% (0.1 of one-sided α and power of 0.8), 25 patients are required (trial identifier NCT03253068).

Between November 2017 and October 2019, a total of 25 patients were enrolled. Most participants (88%) relapsed within 90 days after platinum-containing therapy and all patients were immune checkpoint inhibitor-naive. ORR, the primary end point, was 52.0% (95% confidence interval [CI] 31.3%-72.2%). Median PFS was 4.0 months (95% CI 2.8-7.0 mo), and PFS rate at 1 year was 14.4%. Median overall survival was 10.6 months (95% CI 7.3-21.3 mo). Common adverse events greater than or equal to grade 3 were neutropenia (64%), leukopenia (40%), and febrile neutropenia (16%). No treatment-related deaths occurred.

Among patients with relapsed SCLC, pembrolizumab plus AMR was effective and tolerable.

Among patients with relapsed SCLC, pembrolizumab plus AMR was effective and tolerable.Molecular sequencing after highly potent targeted gene inhibitors have suggested resistant tumors can display substantial heterogeneity. Among these various mechanisms of resistance, secondary mutations on targetable oncogenes have been identified. BRAF V600E, as a bypass mechanism on disease progression while receiving osimertinib therapy, has been reported in 3% of EGFR-mutated patients. Few case reports described the efficacy of the association of osimertinib and dabrafenib plus trametinib. Here, we report, for the first time, a case of a patient treated with this association, with a prolonged response on leptomeningeal metastasis. We also provide a comprehensive overview of the available literature on the efficacy and tolerance of this association.

Since the July 2017 National Comprehensive Cancer Network (NCCN) malignant pleural mesothelioma (MPM) guideline revision recommended second-line immune checkpoint inhibitors (ICIs), studies have suggested a greater response to ICI among patients with nonepithelioid MPM. Nevertheless, little is known regarding adoption of ICI in routine practice and if uptake differs by histologic subtype. Our objectives were to evaluate the real-world uptake of second-line ICI among patients with MPM and to reveal its association with histologic subtype.

This was a multicenter, retrospective cohort study of real-world patients with MPM receiving at least two lines of systemic therapy between 2011 and 2019. We found the uptake of second-line ICI over time and evaluated the association between histologic subtype and ICI use, adjusting for relevant patient demographic and clinical factors.

Among the 426 patients with MPM in our cohort, 310 had epithelioid and 116 nonepithelioid histologic subtype. The median age was 73 yeain this population, reflecting prompt integration of scientific discovery into clinical practice.

The objective of this study was to compare overall survival (OS) between patients with pT1-2N1 versus pT3N0 NSCLC and various subtypes of pT3N0 NSCLC.

The National Cancer Database was queried to identify treatment-naive patients with pathologic stage IIB primary NSCLC. Patients were included if they were diagnosed with pT3N0 or pT1-2N1 NSCLC and received definitive surgery within 4 months of diagnosis. Selleckchem Cyclopamine The pT3N0 cohort was subdivided by single versus multiple concurrent T3 descriptors and single-T3 subtypes. The 5-year OS was compared using the Kaplan-Meier method, and the Cox proportional-hazards model was used to identify prognostic factors for death.

A total of 16,770 patients were included (pT3N0 7179; pT1-2N1 9591). pT3N0 NSCLC was associated with greater 5-year OS than pT1-2N1 NSCLC (52.4% versus 47.8%,

< 0.0001). Among patients receiving adjuvant chemotherapy after surgery, multiple-T3 pT3N0 NSCLC was associated with lower 5-year OS than single-T3 pT3N0 NSCLC (49.0% versus 63.3%,

< 0.le T3 descriptors in pT3N0 NSCLC.

Immune checkpoint inhibitors (ICIs) have become an increasingly important tool in cancer treatment, revealing durable responses in several different types of tumors, including NSCLCs. Nevertheless, ICIs carry a risk of immune-mediated toxicities. There is a paucity of data for concurrent use of these agents in patients with autoimmune disorders, such as multiple sclerosis (MS).

We report a case of a man with a historyof MS and metastatic NSCLC with brain metastases who had cancer progression after receiving chemotherapy, whole-brain radiation therapy, and stereotactic radiosurgery to brain lesions and was treated with the programmeddeath-ligand 1 inhibitor, atezolizumab. He had dramatic clinical and radiographic benefit but developed asevere MS flare and neurologic decline precluding furthertreatment. Considerable growth of a previously radiated brain lesion prompted resection, with pathologic findings consistent with radiation necrosis and demyelination without viable tumor cells.

Although patients with preexisting autoimmune diseases, including MS, might be at an increased risk of developing immune-related adverse events with ICIs, they may also experience anticancer benefit.