scholarly journals AURA3 trial: does Tagrisso (osimertinib) have the potential to become the new standard of care for second-line treatment of patients with EGFR T790M mutation-positive locally advanced or metastatic NSCLC

2016 ◽  
Vol 5 (4) ◽  
pp. 159-162 ◽  
Author(s):  
Vassiliki A Papadimitrakopoulou
Keyword(s):  
Locally Advanced ◽  
Standard Of Care ◽  
Line Treatment ◽  
Second Line ◽  
T790m Mutation ◽  
Metastatic Nsclc ◽  
Egfr T790m

Efficacy of cetuximab after immunotherapy (IO) in advanced cutaneous squamous cell carcinoma (CSCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9562-9562
Author(s):  
Julian Andres Marin-Acevedo ◽  
Bethany Withycombe ◽  
Youngchul Kim ◽  
Zeynep Eroglu ◽  
Joseph Markowitz ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Acquired Resistance ◽  
Standard Of Care ◽  
Line Treatment ◽  
Second Line ◽  
Survival Times ◽  
Entire Cohort ◽  
Overall Response ◽  
Curative Radiotherapy

9562 Background: Anti-PD1 (aPD1) monotherapy with cemiplimab-rwlc or pembrolizumab is now considered standard of care for first-line management of advanced CSCC not amenable to surgery or curative radiotherapy. Previously chemotherapy or anti-EGFR agents were commonly used for these patients albeit with modest efficacy and limited duration of response. In prospective evaluation, the overall response rate (ORR) to cetuximab was 28% with disease control rate (DCR) of 69% at 6 weeks. The efficacy of second-line treatment following primary or acquired resistance to aPD1 therapy is not known. We investigated the activity of cetuximab in patients who progressed on previous IO therapy. Methods: We performed a single institution retrospective review from 9/28/18 (US approval date of cemiplimab-rwlc for CSCC) through 11/30/20 of patients with locally advanced or metastatic CSCC who received cetuximab after prior IO therapy. We identified patients who received cetuximab either immediately following IO therapy (cohort A) or as a subsequent line not immediately following IO therapy (cohort B). Primary endpoint was ORR with secondary endpoints of DCR, survival and toxicity. Median follow-up and survival times were calculated using the Kaplan-Meier method. Results: Thirteen patients, median age 72 years (62-82), all Caucasian, and 11 males (85%) were included in this study. Eleven pts received cetuximab immediately post-IO progression; two had additional intervening therapy post-IO before receiving cetuximab. Three patients received concurrent radiotherapy (palliative or definitive) with cetuximab. The ORR to cetuximab was 54% (7/13) including 1 complete and 6 partial responses. The cumulative 6-month DCR was 77%. All responses were observed in cohort A; both patients in cohort B had progressive disease as best response. Six of 7 initial responses are ongoing, including 3 in whom cetuximab was discontinued. At a median follow-up of 9.1 months, the median PFS has not been reached for the entire cohort. There were no unanticipated toxicities to cetuximab with rash (77%) and hypomagnesemia (54%) being the most common adverse events. Conclusions: In advanced CSCC, cetuximab used immediately after progression on aPD1 therapy yields notably higher and durable overall response than previously reported in the pre-IO therapy era. If validated in a larger dataset, this should be the preferred therapy for second-line treatment in advanced CSCC. Further exploration into the mechanism of this high efficacy of anti-EGFR therapy post aPD1 therapy is warranted.

scholarly journals Paradigm Shifting of Systemic Chemotherapy for Unresectable Pancreatic Cancer in Japan

2019 ◽  
Vol 8 (8) ◽  
pp. 1170 ◽  
Author(s):  
Junji Furuse
Keyword(s):  
Pancreatic Cancer ◽  
Systemic Chemotherapy ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Phase Iii ◽  
Unresectable Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Brca Mutations ◽  
Line Chemotherapy

Systemic chemotherapy plays an important role in the treatment of pancreatic cancer, to improve the survival of patients with pancreatic cancer. Unresectable pancreatic cancer can be classified into three categories: metastatic, locally advanced, and hereditary pancreatic cancers. Furthermore, the second-line chemotherapy is required to prolong the survival. The combined regimens of oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GEM plus nab-PTX) have been recognized as the standard of care for advanced pancreatic cancer. However, the consensus of selection of the first-line chemotherapy still remains. Randomized controlled trials (RCTs) between FOLFIRINOX and GEM plus nab-PTX are ongoing for locally advanced and metastatic disease in Japan, respectively. Hereditary pancreatic cancer, especially associated with BRCA mutations, is responsive to platinum-containing regimens and/or poly (ADP-ribose) polymerase (PARP) inhibitors. It is becoming more important to examine the presence/absence of BRCA mutations to select the appropriate treatment strategy for individual patients. Although some S-1-based regimens have been investigated in the second-line treatment after GEM-based chemotherapy in Japan, no regime demonstrated survival benefit. Nanoliposomal irinotecan (nal-IRI) plus FF has been established as the standard of care in the second-line treatment in a global phase III trial (NAPOLI-1). A randomized phase II trial comparing FF plus nal-IRI with FF alone was also conducted in Japan to examine the efficacy and safety of the FF plus nal-IRI in Japanese patients.

scholarly journals Efficacy and Safety of Pemetrexed and Gefitinib in the Treatment of Non-Small-Cell Lung Cancer: A Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Zhihao Zhang ◽  
Xiyong Wang ◽  
Huaiqing Xiao ◽  
Dongqiang Wu ◽  
Dongliang Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Small Cell ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
Metastatic Nsclc

Object. This study is aimed at evaluating the efficacy and safety of pemetrexed and gefitinib in the treatment of non-small-cell lung cancer (NSCLC). Methods. Databases, including PubMed, the Cochrane Library, Embase, CNKI, and Web of Science, were applied to search for randomized controlled trials (RCTs) about the use of pemetrexed and gefitinib in the second-line treatment of locally advanced and metastatic NSCLC from database foundation to April 2020. Meta-analysis was conducted using the RevMan 5.3 software. Primary outcomes included progression-free survival (PFS) and overall survival (OS), and secondary outcomes included objective response rate (ORR), disease control rate (DCR), and all grades of drug-related adverse events (AEs). Results. Totally, 14 RCTs and 1,334 patients were involved in the study. The results of meta-analysis showed that compared with pemetrexed, gefitinib was not superior in improving ORR ( P = 0.21 ), DCR ( P = 0.52 ), PFS ( P = 0.41 ), and OS ( P = 0.79 ). Subgroup analysis showed that in patients with mutant EGFR ( P = 0.08 ) and wild-type EGFR ( P = 0.80 ), both pemetrexed and gefitinib produced a similar effect on PFS. In terms of safety, the incidence of rash ( P < 0.00001 ) and diarrhea ( P = 0.0005 ) in the gefitinib group was significantly higher than those in the pemetrexed group, while the occurrence of neutropenia ( P = 0.01 ) and fatigue ( P = 0.02 ) was significantly lower. Conclusion. Gefitinib and pemetrexed showed similar efficacy and safety, regardless of the type of EGFR. Both gefitinib and pemetrexed can be used as conventional drugs for the second-line treatment of locally advanced and metastatic NSCLC.

scholarly journals Case Report: Response to Almonertinib in a Patient With Metastatic NSCLC Resistant to Osimertinib due to Acquired EGFR L718Q Mutation

2021 ◽  
Vol 12 ◽  
Author(s):  
Gang Shen ◽  
Lei Shi ◽  
Xin Tian ◽  
Depei Huang ◽  
Hao Chen ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Nonsmall Cell Lung Cancer ◽  
Egfr Mutations ◽  
Clinical Activity ◽  
Line Treatment ◽  
Second Line ◽  
Metastatic Nsclc ◽  
Epidermal Growth ◽  
Nsclc Patients ◽  
Egfr T790m

Osimertinib shows strong clinical activity in first- and second-line treatment of nonsmall-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, especially EGFR T790M. However, when patients develop resistance, there is currently no definite postosimertinib treatment option. Herein, we report a patient with metastatic NSCLC who benefited from almonertinib after developing resistance to osimertinib.

scholarly journals Real-World Pattern of Treatment and Clinical Outcomes of EGFR-Mutant Non-Small Cell Lung Cancer in a Single Academic Centre in Quebec

2021 ◽  
Vol 28 (6) ◽  
pp. 5179-5191
Author(s):  
Jason S. Agulnik ◽  
Goulnar Kasymjanova ◽  
Carmela Pepe ◽  
Manjusha Hurry ◽  
Ryan N. Walton ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Real World ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
T790m Mutation ◽  
Metastatic Nsclc ◽  
Egfr Mutant ◽  
Egfr Tkis ◽  
First Line Treatment

The discovery of EGFR tyrosine kinase inhibitors (TKI) for the treatment of EGFR mutant (EGFRm) metastatic NSCLC is regarded as a landmark in lung cancer. EGFR-TKIs have now become a standard first-line treatment for EGFRm NSCLC. The aim of this retrospective cohort study is to describe real-world patterns of treatment and treatment outcomes in patients with EGFRm metastatic NSCLC who received EGFR-TKI therapy outside of clinical trials. One hundred and seventy EGFRm metastatic NSCLC patients were diagnosed and initiated on first-line TKI therapy between 2004 and 2018 at the Peter Brojde Lung Cancer Centre in Montreal. Following progression of the disease, 137 (80%) patients discontinued first-line treatment. Moreover, 80/137 (58%) patients received second-line treatment, which included: EGFR-TKIs, platinum-based, or single-agent chemotherapy. At the time of progression on first-line treatment, 73 patients were tested for the T790M mutation. Moreover, 30/73 (41%) patients were found to be positive for the T790M mutation; 62/80 patients progressed to second-line treatment and 20/62 were started on third-line treatment. The median duration of treatment was 11.5 (95% CI; 9.62–13.44) months for first-line treatment, and 4.4 (95% CI: 1.47–7.39) months for second-line treatment. Median OS from the time of diagnosis of metastatic disease was 23.5 months (95% CI: 16.9–30.1) and median OS from the initiation of EGFR-TKI was 20.6 months (95% CI: 13.5–27.6). We identified that ECOG PS ≤ 2, presence of exon 19 deletion mutation, and absence of brain metastases were associated with better OS. A significant OS benefit was observed in patients treated with osimertinib in second-line treatment compared to those who never received osimertinib. Overall, our retrospective observational study suggests that treatment outcomes in EGFRm NSCLC in real-world practice, such as OS and PFS, reflect the result of RCTs. However, given the few observational studies on real-world treatment patterns of EGFR-mutant NSCLC, this study is important for understanding the potential impact of EGFR-TKIs on survival outside of clinical trials. Further real-world studies are needed to characterize patient outcomes for emerging therapies, including first-line osimertinib use and combination of osimertinib with chemotherapy and potential future combination of osimertinib and novel anticancer drug, outside of a clinical trial setting.

Penpulimab in combination with anlotinib as first-line treatment in advanced nonsquamous non-small-cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21072-e21072
Author(s):  
Baohui Han ◽  
Jianhua Chen ◽  
Ziping Wang ◽  
Xingya Li ◽  
Lin WANG ◽  
...  
Keyword(s):  
Overall Survival ◽  
Combination Therapy ◽  
Advanced Nsclc ◽  
Locally Advanced ◽  
Drug Binding ◽  
Line Treatment ◽  
First Line ◽  
Anaplastic Lymphoma ◽  
Metastatic Nsclc ◽  
First Line Treatment

e21072 Background: Penpulimab is a human IgG1 monoclonal antibody (mAb) directed against human programmed cell death-1 (PD-1). Penpulimab, with its unique binding epitope, was engineered to eliminate Fc-mediated effector function that compromises anti-tumor immune cell function, and to optimize receptor occupancy by improving duration of drug binding. As a promising multi-target tyrosine kinase inhibitor (TKI), anlotinib significantly improved overall survival in advanced NSCLC patients (pts) in the phase 3 trial ALTER0303. Antiangiogenesis therapy combined with PD-1/PD-L1 inhibitors has shown excellent efficacy in advanced NSCLC pts. This is the trial evaluating chemo-free combination of penpulimab plus anlotinib in treatment-naive advanced NSCLC pts regardless of PD-L1 expression (NCT03866980). Methods: Pts with previously untreated, stage IIIB/IIIC/IV non-squamous NSCLC without sensitizing mutation of the epidermal growth factor receptor (EGFR) gene or translocation of the anaplastic lymphoma kinase (ALK) gene were enrolled. Eligible pts received penpulimab 200mg Q3W in combination with anlotinib 12mg QD (2 weeks on 1 week off) until loss of clinical benefit or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included ORR, disease control rate (DCR), duration of response (DoR) and overall survival. Results: As of January 13, 2021, 26 pts had received the combination therapy of penpulimab plus anlotinib (median age 59.5yrs [range 30-71], 76.9% male, 76.9% ECOG PS 1), with a median treatment duration of 3.5 months. Of 21 pts who have had at least one tumor assessment, the ORR was 57.1% (12 PRs) and DCR was 90.5% (12 PRs, 7 SDs). Median PFS has not been reached, and eleven responders remain in response. Treatment-related adverse events (TRAEs) occurred in 53.8% of pts (≥G3 TRAEs occurred in 15.4% [4/26]). Treatment-related SAEs occurred in 15.4% [4/26], and 7.7% of pts [2/26] had drug interruption or discontinuation due to TRAEs. Most common TRAEs (≥15%) were ALT increased, AST increased, hyperthyroidism and hypertension (15.4% each). Conclusions: The combination of penpulimab plus anlotinib as first-line treatment for locally advanced/metastatic NSCLC showed the promising efficacy with a manageable safety profile, thereby suggesting that this combination therapy may be a viable chemo-free treatment strategy for locally advanced/metastatic NSCLC pts. Clinical trial information: NCT03866980.

scholarly journals Second-Line Treatment of HER2-Positive Salivary Gland Tumor: Ado-Trastuzumab Emtansine (T-DM1) after Progression on Trastuzumab

2018 ◽  
Vol 11 (2) ◽  
pp. 252-257 ◽  
Author(s):  
Tatiana Strava Corrêa ◽  
Gustavo Duarte Ramos Matos ◽  
Marcos Segura ◽  
Carlos Henrique dos Anjos
Keyword(s):  
Disease Progression ◽  
Radical Neck Dissection ◽  
Locally Advanced ◽  
Pet Scan ◽  
Bone Lesions ◽  
Her2 Overexpression ◽  
Line Treatment ◽  
Second Line ◽  
Her2 Positive ◽  
Neck Lymph Node

Patients with salivary duct cancer (SDC) and HER2 overexpression could receive trastuzumab in combination with chemotherapy for metastatic disease. No standard treatment exists for patients with HER2-positive metastatic SDC after progression. We report an excellent patient response to second-line treatment with T-DM1 after progression on paclitaxel plus trastuzumab. Case Report: In June 2014, a 79-year-old male patient underwent right parotidectomy and ipsilateral radical neck dissection after the diagnosis of parotid carcinoma. Pathological staging demonstrated locally advanced disease with the involvement of 13 lymph nodes (levels I, II, III, and IV), with extracapsular extravasation. He underwent adjuvant radiotherapy ending in December 2014. A PET scan in March 2015 diagnosed recurrent and systemic disease, with bone lesions, neck lymph node involvement, and hepatic metastasis. The immunohistochemistry showed HER2 receptor overexpression (+3/+3). The patient received first-line trastuzumab plus paclitaxel beginning in April 2015. After 6 cycles, his response was confirmed by PET scan. In February 2016, he had symptoms of disease progression, and a PET scan revealed disease progression in the neck, bones, and liver. He started T-DM1 in April 2016. The neck skin lesions disappeared after 6 cycles, with low toxicity. PET scans performed every 3 months showed response in the liver and bone lesions. Conclusions: We report the case of a patient with SDC treated with T-DM1, with a very good response. Salivary carcinoma is a rare disease for which no randomized clinical trials are available. The maintenance of HER2 blockage might be important in this disease.

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