- |||||||||| Lorbrena (lorlatinib) / Pfizer, Xalkori (crizotinib) / Pfizer, Alecensa (alectinib) / Roche
Cost of Managing Brain Metastases in Patients with ALK+ aNSCLC with First-Line Tyrosine Kinase Inhibitors (TKIs) in the UK (Exhibit Hall) - Jul 25, 2023 - Abstract #IASLCWCLC2023IASLC_WCLC_2309;
This study demonstrates the direct relationship between the lower cumulative incidence of progression of BM and lower cost burden in patients with ALK+ NSCLC receiving 1L TKIs in the UK. Where data are available in patients without baseline BM, due to the lower 12-month and 24-month cumulative incidence of progression of BM with lorlatinib, its management cost PPY is lower than that of alectinib.
- |||||||||| Real-World Outcome of Metastatic ALK-Positive Non-Small Cell Lung Cancer Treated with Tyrosine Kinase Inhibitors (Exhibit Hall) - Jul 25, 2023 - Abstract #IASLCWCLC2023IASLC_WCLC_2308;
Patients with advanced ALK-positive NSCLC have prolonged survival after the introduction of ALK TKIs with a median OS that exceeds 5 years when ALK TKIs are used in the first-line setting. Re-biopsies during treatment are needed to enhance our understanding of resistance mechanisms and the tumor dynamics that develop during ALK TKI therapy and to increase individualized management of this disease within precision medicine.
- |||||||||| Alecensa (alectinib) / Roche
NAUTIKA1 Study: Preliminary Efficacy and Safety Data with Neoadjuvant Alectinib in Patients with Stage IB-III ALK+ NSCLC (Exhibit Hall) - Jul 25, 2023 - Abstract #IASLCWCLC2023IASLC_WCLC_2191;
P2
In this preliminary analysis from NAUTIKA1, neoadjuvant alectinib demonstrated major pathological response and was well tolerated in patients with ALK+ NSCLC. Further analyses with 12 patients will be available at the conference presentation.Baseline characteristics (N=8)Age (years), median (range)52 (35-75)Sex, nFemale / Male6 / 2Race, nAsian / White / Unknown1 / 4 / 3Smoking history, nYes / No3 / 5ECOG PS, n0 / 15 / 3Non-metastatic lung cancer histology, nAdenocarcinoma / Squamous cell carcinoma7 / 1Clinical staging (AJCC 8th edition), nStage IIA / IIB / IIIA / IIIB1 / 1 / 5 / 1Neoadjuvant treatment exposure (N=8)Treatment duration (weeks), median (range)8.0 (6.7-8.7)Pathological response (N=7)* Major pathological response, n/N (%) [95% CI]5/7 (71.4) [29.0-96.3]Pathological complete response, n/N (%) [95% CI]2/7 (28.6) [3.7-71.0]Radiographic response (N=8)Objective response rate (by investigator), n/N (%) [95% CI]2/8 (25) [3.2-65.1]Complete response0 [0-36.9]Partial response2/8 (25) [3.2-65.1]Stable disease6/8 (75) [34.9-96.8]Progressive disease0 [0-36.9]Surgical outcomes (N=7)Days from first neoadjuvant treatment to surgery,median (range)62.0 (57.0-71.0)Days from last neoadjuvant treatment to surgery,median (range)6.0 (1.0-16.0)Surgical delays due to adverse events, n0Surgery type, nMinimally invasive surgery / open approach6 / 1Unplanned surgery conversion, n2Duration of surgery (minutes), median (range)245.0 (104.0-386.0)Days in hospital, median (range)4.0 (0.0-8.0)R0 resection, n6Aborted resection, n1Resection approach, nRobotically assisted VATS / Thoracotomy / VATS2 / 1 / 3Extent of resection, nLeft upper lobectomy / Right lower lobectomy / Right upper lobectomy2 / 2 / 2Intraoperative events (N=7)Intraoperative complications / injury, n0Estimated blood loss (mL), median (range)100.0 (20.0-650.0)Intraoperative fibrosis, n3Intraoperative lymphadenopathy, n3Type of lymphadenopathy, nBoth N1 and N2 / N1 only / N2 only1 / 1 / 1Severity of lymphadenopathy, nGrade 0 (<1 cm) / Grade 1 (1-<2 cm) / Grade 2 (2-3 cm)4 / 2 / 1Peripheral adhesions, n2Peri-hilar/lobar adhesions, n2Severity of peri-hilar/lobar adhesions, nGrade 1 / Grade 21 / 1AJCC, American Joint Committee on Cancer; ECOG PS, Eastern Cooperative Oncology Group Performance Status; VATS, video-assisted thoracoscopic surgery.*Pathological response was assessed locally; The patient with the squamous histology had a pathological complete response; Physician decision to removeone patient from study during the neoadjuvant phase due to ineligibility; Surgery was aborted due to the need for pneumonectomy.
- |||||||||| Xalkori (crizotinib) / Pfizer, Alecensa (alectinib) / Roche
Neoadjuvant Targeted Therapy for Resectable ALK-fusion Locally Advanced Non-small Cell Lung Cancer (Exhibit Hall) - Jul 25, 2023 - Abstract #IASLCWCLC2023IASLC_WCLC_2187;
We enrolled 11patients from January 2019 to December 2022 at the Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute with stage IIB-IIIB ALK-positive NSCLC who received Crizotinib or Alectinib as inductive treatment strategy before surgery. Targeted therapy is a feasible and well tolerated therapy, and it may be an optimal induction strategy for resectable ALK-rearranged locally advanced non-small cell lung cancer
- |||||||||| Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
Sequencing Patterns and Treatment Effectiveness in ALK-positive aNSCLC Following First-Line Alectinib or Brigatinib (Exhibit Hall) - Jul 25, 2023 - Abstract #IASLCWCLC2023IASLC_WCLC_1771;
Approximately one-third of patients did not receive a second-line treatment, mostly due to death. Coupled with the observation that treatment duration was shorter in second-line than first-line and median total time on sequential ALKi therapy was less than 3 years, the most efficacious treatment in ALK-positive aNSCLC should be used upfront.
- |||||||||| Lorbrena (lorlatinib) / Pfizer, Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
Comparative Efficacy and Safety of Lorlatinib vs Alectinib and Brigatinib Using Matching Adjusted Indirect Comparisons (MAIC) (Exhibit Hall) - Jul 25, 2023 - Abstract #IASLCWCLC2023IASLC_WCLC_1766;
While the risk of grade 3+ AEs was higher with lorlatinib compared to alectinib (ALEX, ALESIA), there were no differences in other safety endpoints or compared to brigatinib. Overall, this study bolsters the totality of evidence on the comparative efficacy and safety of lorlatinib as a first-line treatment for ALK+ aNSCLC.
- |||||||||| Lorbrena (lorlatinib) / Pfizer, Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
Treatment Patterns and Economic Burden of Brain Metastases (BM) in Patients with ALK+ mNSCLC Receiving ALK TKIs (Exhibit Hall) - Jul 25, 2023 - Abstract #IASLCWCLC2023IASLC_WCLC_1762;
BM diagnosis was associated with a high cost burden, with increases in PPPM total medical costs pre- vs post-BM. These results underscore the need for therapeutic strategies in 1L setting to delay or prevent BM occurrence and to lessen its burden among patients with ALK+ NSCLC.
- |||||||||| Tecentriq (atezolizumab) / Roche, Alecensa (alectinib) / Roche
Journal, PD(L)-1 Biomarker, IO biomarker: External validation of a tumor growth inhibition-overall survival model in non-small-cell lung cancer based on atezolizumab studies using alectinib data. (Pubmed Central) - Jul 24, 2023
The progression rate was lower in alectinib than the crizotinib patients, although there were more patients with multiple metastases and brain metastases in the alectinib arm. The TGI-OS model based on unselected or PD-L1 selected NSCLC patients included in atezolizumab trials is externally validated to predict treatment effect (HR) in a biomarker-selected (ALK-positive) population included in alectinib ALEX trial suggesting that TGI-OS models may be treatment independent.
- |||||||||| Xalkori (crizotinib) / Pfizer, Alecensa (alectinib) / Roche
Retrospective data, Journal, Real-world evidence, Real-world: ALK Inhibitor Treatment Patterns and Outcomes in Real-World Patients with ALK-Positive Non-Small-Cell Lung Cancer: A Retrospective Cohort Study. (Pubmed Central) - Jul 17, 2023
We found that ALK TKIs were highly tolerable, and alectinib was associated with favorable survival outcomes with longer time to adverse events (AE) requiring medical interventions, disease progression, and death, in the context of real-world use. Proactive monitoring for adverse events such as rash, bradycardia, and hepatotoxicity may help further promote the safe and optimal use of ALK TKIs in the treatment of patients with aNSCLC.
- |||||||||| Lorbrena (lorlatinib) / Pfizer, Alecensa (alectinib) / Roche
Journal: ALESIA 5-Year Update: Alectinib at 600 mg Twice Daily Gives Lorlatinib a Run for Its Money in Asia. (Pubmed Central) - Jul 13, 2023
Alectinib, a next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), has demonstrated superior progression-free survival over crizotinib with both 300 mg twice daily (J-ALEX) or 600 mg twice daily (ALEX, ALESIA) dosing in three pivotal clinical trials...Importantly, lorlatinib, another next generation ALK TKI, also achieved an impressive hazard ratio with a still immature PFS in all patients, including Asian patients, in a recent subgroup analysis after a median follow-up time of 36.7 months. We await the final mature PFS of lorlatinib overall and for Asian patients in the CROWN trial to see if lorlatinib will set a new standard.
- |||||||||| Review, Journal, Adverse drug reaction: Expert consensus of management of adverse drug reactions with anaplastic lymphoma kinase tyrosine kinase inhibitors. (Pubmed Central) - Jul 3, 2023
The therapeutic use of this class of medications still carries some risk because there are currently no pertinent guidelines or consensus recommendations for managing ADRs caused by ALK-TKIs in China. In order to improve the clinical management of ADRs with ALK-TKIs, the Chinese Society of Clinical Oncology (CSCO) Non-small Cell Lung Cancer Professional Committee led the discussion and summary of the incidence, diagnosis and grading standards, and prevention and treatment of ADRs caused by ALK-TKIs.
- |||||||||| Alecensa (alectinib) / Roche
Trial primary completion date, Metastases: Alectinib Pharmacokinetic in Patients With NSCLC (clinicaltrials.gov) - Jun 27, 2023
P1/2, N=45, Recruiting,
In order to improve the clinical management of ADRs with ALK-TKIs, the Chinese Society of Clinical Oncology (CSCO) Non-small Cell Lung Cancer Professional Committee led the discussion and summary of the incidence, diagnosis and grading standards, and prevention and treatment of ADRs caused by ALK-TKIs. Trial primary completion date: May 2023 --> Nov 2023
- |||||||||| Journal: Clinical Relevance of High Plasma Trough Levels of the Kinase Inhibitors Crizotinib, Alectinib, Osimertinib, Dabrafenib, and Trametinib in NSCLC Patients. (Pubmed Central) - Jun 22, 2023
For alectinib, high Cmin,ss was correlated with a higher risk of DLT. No differences in the frequency of DLTs were observed between the high and non-high groups for crizotinib, osimertinib, dabrafenib, and trametinib.
- |||||||||| Lorbrena (lorlatinib) / Pfizer
Preclinical, Review, Journal, Metastases: From preclinical efficacy to 2022 updated CROWN trial, lorlatinib is the preferred 1-line treatment of advanced ALK+ NSCLC. (Pubmed Central) - Jun 12, 2023
No abstract available Six ALK TKIs (crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, ensartinib) have received first-line treatment indication of advanced ALK+
- |||||||||| Xalkori (crizotinib) / Pfizer, Tecentriq (atezolizumab) / Roche, Alecensa (alectinib) / Roche
Journal, HEOR, PD(L)-1 Biomarker, Cost-effectiveness, Cost effectiveness: Distributional Cost-Effectiveness Analysis of Treatments for Non-Small Cell Lung Cancer: An Illustration of an Aggregate Analysis and its Key Drivers. (Pubmed Central) - Jun 10, 2023
Further research is warranted to examine the value of the opportunity cost threshold, capture the public's views on unfair differences in health, and estimate robust distributional weights incorporating the public's preferences. Finally, guidance from health technology assessment organisations, such as NICE, is needed regarding methods for DCEA construction and how they would interpret and incorporate those results in their decision making.
- |||||||||| Alecensa (alectinib) / Roche
Journal: Alectinib rescue therapy in advanced ALK rearranged lung adenocarcinoma: a case report. (Pubmed Central) - Jun 8, 2023
Alectinib is a highly selective tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that is approved as first-line treatment in adult patients with ALK-positive non-small cell lung cancer (NSCLC) and as second-line in patients previously treated with crizotinib, and has been shown in the literature to significantly prolong progression-free survival compared to chemotherapy in patients with advanced non-small cell lung cancer. The authors describe a clinical case of a 24-year-old woman with malignant massive pleural effusion caused by ALK rearranged pulmonary adenocarcinoma with pleural and pericardial metastasis, in which, despite a dramatic clinical debut, the correct and timely management of the diagnostic and therapeutic path allowed for extraordinary therapeutic success.
- |||||||||| Trial completion, Tumor mutational burden, Metastases: My Pathway: A Study Evaluating Herceptin/Perjeta, Tarceva, Zelboraf/Cotellic, Erivedge, Alecensa, and Tecentriq Treatment Targeted Against Certain Molecular Alterations in Participants With Advanced Solid Tumors (clinicaltrials.gov) - Jun 7, 2023
P2a, N=670, Completed,
The authors describe a clinical case of a 24-year-old woman with malignant massive pleural effusion caused by ALK rearranged pulmonary adenocarcinoma with pleural and pericardial metastasis, in which, despite a dramatic clinical debut, the correct and timely management of the diagnostic and therapeutic path allowed for extraordinary therapeutic success. Active, not recruiting --> Completed
- |||||||||| Lorbrena (lorlatinib) / Pfizer, Alecensa (alectinib) / Roche
Journal, Real-world evidence, Real-world: Real-world therapeutic effectiveness of lorlatinib after alectinib in Japanese patients with ALK-positive NSCLC. (Pubmed Central) - Jun 5, 2023
mDOTs of 147?days (95% CI, 113-242) and 244?days (95% CI, 109 to not reached) were reported with second-line and third- or later-line treatment, respectively. Consistent with clinical trial data, this real-world observational study supports data suggesting the effectiveness of lorlatinib after alectinib failure in Japanese patients.
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