Alecensa (alectinib) / Roche - LARVOL DELTA

Comprehensive genomic profiling to guide personalized targeted and immunotherapy in gastrointestinal tumors: Subgroup analysis of the ROME trial (ESMO-GI 2025) - P2 | "Funding: Erlotinib, Pertuzumab, Vemurafenib, Trastuzumab Emtansine, Alectinib, Vismodegib, Cobimetinib, Atezolizumab, Trastuzumab, Ipatasertib (GDC-0068), Entrectinib and Pralsetinib were provided by Roche; Everolimus, Lapatinib, Alpelisib were provided by Novartis, Palbociclib and Talazoparib were provided by Pfizer, Ipilimumab and Nivolumab were provided by Bristol Myers Squibb (BMS); Brigatinib was provided by Takeda Pharmaceutical Co.; Ponatinib, Itacitinib (INCB039110), Pemigatinib (INCB054828) were provided by Incyte; Selpercatinib was provided by Eli Lilly; Tepotinib was provided by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). CGP with MTB-guided TT may identify patients with GI cancer who benefit from targeted therapies not routinely available in clinical practice. The roles of TMB and potential disease-specific thresholds deserve further investigation."

IO biomarker • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • TMB

Sensitive analysis of tyrosine kinase inhibitors in plasma using polypropylene fabric-solid phase extraction combined with liquid chromatography-tandem mass spectrometry. (PubMed, J Chromatogr A) - "Integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS), the method enabled sensitive determination of eight clinically relevant TKIs (afatinib, alectinib, ceritinib, dasatinib, sunitinib, pazopanib, tamoxifen, and ibrutinib) in plasma. Its practical applicability was validated in spiked plasma under a single-blind design, yielding relative errors of -8.2 % to 5.4 %. Compared to traditional SPE methods, PPF-SPE offers significant advantages in operational simplicity, cost-effectiveness, high throughput, and environmental sustainability."

Journal

Precision medicine in colorectal cancer: Personalizing treatment for improved outcomes? (ESMO-GI 2025) - "Other MTT: KRAS G12C inhibitor + Cetuximab (N=18), pan-RAS inhibitor for KRAS G12Cm (N=1), Encorafenib + Cetuximab (N=14) and Dabrafenib + Trametinib (N=1) for BRAF V600Em, Trastuzumab Deruxtecan (N=3) and Tucatinib + Trastuzumab for HER2m/a (N=1), Trametinib for MEKm (N=2), anti LGR5-EGFR bispecific antibody for EGFRm (N=1), Niraparib + Dostarlimab for ARID1Am (N=1), Alectinib for ALKf(N=1) and Inavolisib for PIK3CAm (N=1). Despite no obvious OS benefit of MTT due to small pts number and late MTT lines, this study highlights the different potential targetable MA in 28.9% of pts excluding non G12C RASm. Impact of novel RAS inhibitors and other MTT might change mCRC precision medicine."

IO biomarker • Colorectal Cancer • Oncology • Solid Tumor • ALK • ARID1A • BRAF • KRAS

Final Analysis of Brighstar: LCT With Brigatinib in Tyrosine Kinase Inhibitor-Naïve ALK-Rearranged Metastatic NSCLC (IASLC-WCLC 2025) - P1, P3 | "Individual patient data from a phase 3 trial of brigatinib vs crizotinib (ALTA-1L, NCT02737501) were retrospectively compared...One patient with grade 3 pneumonitis successfully transitioned to full-dose alectinib after resolution with corticosteroids...Conclusions : Brigatinib with LCT is safe in patients with ALK-rearranged advanced NSCLC and yielded promising results when compared to historical outcomes from brigatinib alone. Patients who received comprehensive LCT had superior outcomes, and baseline ctDNA status and radiological volumetric measurements may serve as prognostic biomarkers for treatment response."

Metastases • Anemia • Endocrine Disorders • Gastrointestinal Disorder • Hematological Disorders • Lung Cancer • Nephrology • Non Small Cell Lung Cancer • Pneumonia • Renal Disease • Solid Tumor • ALK

Real-world costs, treatment patterns, and clinical outcomes associated with treatments for advanced anaplastic lymphoma kinase-positive non-small cell lung cancer. (PubMed, J Manag Care Spec Pharm) - "Among 696 patients, the 1L therapy distribution was crizotinib (n = 366), alectinib (n = 267), brigatinib (n = 22), ceritinib (n = 25), and lorlatinib (n = 16). This study highlights the economic burden and variable clinical outcomes among patients with advanced ALK+ NSCLC. These real-world estimates inform cost-effectiveness analyses and clinical decision-making regarding treatment sequencing, particularly given uncertainty surrounding multiple preferred 1L options in clinical guidelines."

Clinical data • Journal • Observational data • Real-world evidence • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

ProTarget - A Danish Nationwide Clinical Trial on Targeted Cancer Treatment Based on Genomic Profiling (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Ulrik Lassen | Trial completion date: Apr 2025 ➔ Apr 2030 | Trial primary completion date: Apr 2024 ➔ Apr 2029

Trial completion date • Trial primary completion date • Oncology

ALK inhibitors against resistance in non-small cell lung cancer: an 18 year medical arms race. (PubMed, Biochem Pharmacol) - "This review presents a timeline-based approach to understanding how drug development has tackled ALK inhibitor resistance, by integrating key historical developments with resistance mechanisms, and evolving treatment strategies; by discussing the discovery of ALK rearrangements, exploring the molecular underpinnings of resistance, and latest advances in combination therapies and fourth-generation inhibitors. By aligning biological and pharmacological milestones with therapeutic progress this review provides a structured overview of how the field has evolved and where future efforts are directed."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

A Study of Alectinib and Duvelisib in People With Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma (ALK+ALCL) (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Non-Hodgkin’s Lymphoma • Oncology

Alectinib Efficacy Post-Brigatinib Against Advanced ALK+ Non-Small Cell Lung Cancer (BrigALK2-GFPC 02-2019 Study). (PubMed, Lung Cancer (Auckl)) - "Brigatinib and alectinib are next-generation anaplastic lymphoma kinase inhibitors (ALKis) showing efficacy against naïve and post-crizotinib-treated advanced ALK+ non-small-cell lung cancers (NSCLCs). For patients receiving ≥1 agent(s) between brigatinib and alectinib, with median follow-up at 13.3 (95% CI: 2.3-31.5) months, mPFS and mOS were 5.0 (95% CI: 0.5-18.8) and 19 (95% CI: 2.3-NR) months, respectively. According to the results of this retrospective real-world study, alectinib post-brigatinib showed limited overall activity but remains an option for patients with advanced ALK+ NSCLCs, especially when brigatinib was discontinued because of toxicity."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

A real-world pharmacovigilance analysis of ALK inhibitor-associated pleural and pericardial effusion using the FDA Adverse Events Reporting System (FAERS) database from 2013 to 2024. (PubMed, PLoS One) - "This study highlights the critical need for vigilant pharmacovigilance and a multidisciplinary approach to balance the oncologic benefits of ALK inhibitors against their cardiopulmonary risks. By enhancing awareness and fostering proactive management, these findings aim to support the safe and effective use of ALK inhibitors in treating ALK-rearranged malignancies."

Adverse events • Journal • Real-world evidence • Cardiovascular • Oncology • ALK

Pralsetinib (Phase 1/2 ARROW Trial) Compared With Best Available Therapy (External Control) in Pretreated RET Fusion+ NSCLC (IASLC-WCLC 2025) - P1/2 | "Most frequently received BAT were tyrosine kinase inhibitors (66.7%; 29.6% investigational agents, 25.9% cabozantinib, 7.4% vandetanib, 3.7% alectinib) and chemotherapy (25.9%)...Conclusions : This RW, multi-center study found that 2L+ treatment with pralsetinib in advanced RET fusion-positive NSCLC was associated with higher ORR and significantly improved OS and PFS compared to BAT, even after adjusting for population differences. Limitations of RW data include missing data and potential unmeasured confounding, which this study aimed to mitigate through rigorous analytical methods."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • RET

Real-World Impact on Overall Survival of High-Cost Targeted and Immunotherapies in Lung Cancer Patients Under Chile's DAC Program (IASLC-WCLC 2025) - "Patients were evaluated according to the medication received (immunotherapies: Pembrolizumab, Nivolumab; and tyrosine kinase inhibitors: Osimertinib, Alectinib, Crizotinib). This limitation may partially explain variations observed in survival between immunotherapy-treated patient groups and should be considered when interpreting these results.The presence of heterogeneous histologies (adenocarcinoma and squamous cell carcinoma) among patients treated with immunotherapy could influence differential responses and survival outcomes, highlighting the need for future, more detailed subgroup analyses. Additionally, age and cancer staging are critical factors known to influence survival significantly and should be included in subsequent analyses to provide a clearer interpretation of the impact of DAC-funded treatments.Despite these limitations, the data confirm the clinical relevance of DAC by facilitating access to high-cost drugs and underscore the importance of conducting..."

Clinical • Real-world • Real-world evidence • Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

Weight Gain Induced by Tyrosine Kinase Inhibitors in Oncogene-Addicted Non-Small Cell Lung Cancer: A Meta-Analysis and a Meta-Regression Study (IASLC-WCLC 2025) - "Lorlatinib showed the highest risk for treatment-induced WG [incidence 36%; 95% CI: 26%-46%; I2=92%], followed by alectinib [incidence 15%; 95% CI: 26%-46%; I2=52%] and crizotinib [incidence 5%; 95% CI: 0%-13%; I2=93%] [ Figure 1 ]. Osimertinib and erlotinib showed the lowest incidence of WG...Considering the impressive prognostic horizons achievable with TKIs in OA NSCLC, adequate reporting of WG in clinical trials, as well as assessment/monitoring of WG, body composition modifications and impact on QoL should be prioritize, together with adequate lifestyle-based strategies for its management. $$graphic_9D18D1E6-2D92-4873-9823-3347FBAD9F40$$"

Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

N3 Stage May no Longer Be Considered Unresectable in Anaplastic Lymphoma Kinase(ALK)-Positive Non-Small Cell Lung Cancer: A Case Series (IASLC-WCLC 2025) - "The patient first received three cycles of docetaxel plus cisplatin, and the treatment response was evaluated as stable disease (SD).After multidisciplinary team (MDT) discussion, the treatment regimen was modified to crizotinib. By the time of manuscript submission, the patient had not experienced recurrence, with PFS and OS of 38 months. Conclusions : These case sheds light on the feasibility and safety of alectinib and crizotinib as a conservsion treatment and the efficacy of for stage N3 NSCLC patients with ALK rearrangement."

Clinical • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Enhancing Alectinib Efficacy in ALKPositive Non-Small Cell Lung Cancer by Targeting Mtor (IASLC-WCLC 2025) - "Methods : ALK-rearranged cancer cell lines CUTO8, CUTO9, CUTO29.1, CUTO39, CUTO41, CUTO43, CUTO46, DFCI032, NCI-H2228, NCI-H3122, SNU2292, SNU2535, and EA2 were treated with Alectinib alone or in combination with Everolimus. Conclusions : These findings provide strong evidence that mTOR inhibition is a promising strategy to enhance the effectiveness of Alectinib, potentially overcoming some resistance mechanisms in ALK-positive non-small cell lung cancer (NSCLC) and enhancing Alectinib efficacy. Taken together, these studies in multiple cell models provide a strong rationale for further in vivo validation and clinical exploration to improve outcomes for patients."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Rebiopsy in Oncogene-Driven Lung Cancer: Real-World Practices in ALK, EGFR, and ROS1 Cohorts in the Australian AURORA Longitudinal Cohort Study (IASLC-WCLC 2025) - P | "Focussed on current treatments within a manageable cohort size, EGFR was limited to patients receiving first-line osimertinib...Among ALK+ patients, the most common first-line treatments were alectinib (26%, 37/141), crizotinib (24%, 34/141), chemotherapy (20%, 29/141), and lorlatinib (12%, 17/141)...Among ROS1+ patients, first-line treatments included entrectinib (23%, 8/35), crizotinib (23%, 8/35), and chemotherapy (20%, 7/35)...Re-biopsy at progression increased over time with evolving evidence of benefit, increasing opportunities for personalised treatment selection. Improved access to funded liquid re-biopsy may further improve rates."

Clinical • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

A Comprehensive Analysis of Front-Line Regimens for Stage IV Non-Squamous Non-Small Cell Lung Cancer: A 13-Year Experience (IASLC-WCLC 2025) - "The most common regimens were carboplatin + pemetrexed/paclitaxel (N = 502, 80%) and bevacizumab + carboplatin + pemetrexed/paclitaxel (N = 127, 20%) for CTX, pembrolizumab (N = 167, 89%) for IT and carboplatin + pemetrexed + pembrolizumab (N = 153, 41%) for chemo-IT...Using multivariable CPH, front-line Osimertinib (N = 81) was associated with improved OS compared to erlotinib (N =93) in EGFR mutated NS NSCLC (HR 0.59, 95%CI 0.42-0.84 p = 0.003) but not afatinib (n=26) (HR 0.80, 95%CI 0.48-1.33, p = 0.013). In ALK mutated NS NSCLC, multivariable CPH showed that front-line crizotinib (N =20) was associated with worse OS than alectinib (N = 28) (HR 4.4, 95%CI 1.87-10.6, p < 0.001) Conclusions : In the largest retrospective study of stage IV NS NSCLC, we confirmed that modern regimens improved OS by 28% compared to conventional CTX. Despite that, long term survival remains poor and further research is needed."

IO biomarker • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • PD-L1

A Real-World Efficacy and Safety Analysis of Alectinib Versus Crizotinib as Adjuvant Therapy in Resectable ALK-Positive Non-Small-Cell Lung Cancer (ESMO 2025) - No abstract available

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Contemporary Landscape of Acquired Resistance to Next-Generation ALK Inhibitors: Paired Pre-/Post-Treatment Biopsy Analysis (IASLC-WCLC 2025) - "Methods : This retrospective study included patients treated with second-generation (2G; alectinib, brigatinib, ceritinib) and/or third-generation (3G; lorlatinib) ALK TKIs with paired (pre- and post-TKI) biopsies assessed with next-generation sequencing (NGS)...Among patients without prior crizotinib, MET amplification was more frequent on post- versus pre-lorlatinib biopsies (22.2% vs 2.8%, p=0.016)...MET amplification represents a recurrent off-target AR mechanism and highlights the critical role for post-TKI biopsies to enable consideration of ALK/MET co-inhibition. NGS does not identify putative AR mechanisms for significant proportion of patients, emphasizing a need to investigate non-genomic AR mechanisms."

Biopsy • Preclinical • Lung Cancer • Oncology • Solid Tumor • ALK • CDKN2A • CDKN2B • EGFR • KEAP1 • MET • NF1 • NOTCH2 • SETD2 • SMAD4 • SMARCA4 • TP53

Benefits of Adjuvant Alectinib in ALK+ Early-Stage Non-Small Cell Lung Cancer, Recurrences Avoided and Savings for the Spanish Health System (IASLC-WCLC 2025) - "Scenario sensitivity analyses provided a range of 42,3 to 49,3 million euros of savings. Conclusions : The use of adjuvant alectinib in patients with resected ALK+ eNSCLC would substantially reduce the number of recurrences over the next 10 years, resulting in significant cost savings in the management of the advanced disease for the Spanish National Healthcare System."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

ML44840: A Multicenter Prospective Cohort Study of the Patient-Reported Outcomes in Chinese Patients With ALK+ Advanced NSCLC (IASLC-WCLC 2025) - P | "Approximately 800 patients with ALK-positive locally advanced or metastatic NSCLC will be enrolled into 3 parallel cohorts from both traditional sites and Direct to Patient (DTP) Pharmacies: Alectinib Cohort(n=400), Lorlatinib cohort(n=200) and other approved ALK-TKIs cohort(n=200), by the treating physician's decision. The primary endpoint is PRO related outcome. The secondary endpoint is safety."

Clinical • Metastases • Patient reported outcomes • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK

Insights on Treatment Experience From Patients With ALK+ NSCLC Treated With 1St-Line Brigatinib, Lorlatinib and Alectinib (IASLC-WCLC 2025) - "These data illustrate the multifaceted impact of ALK-TKI treatment on daily life, highlighting the importance of addressing both physical and psychosocial dimensions of patient care. These findings emphasize the importance of patient experience considerations in treatment decisions for ALK+ NSCLC."

Clinical • Asthma • Fatigue • Gastroesophageal Reflux Disease • Immunology • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Pneumonia • Respiratory Diseases • Solid Tumor • ALK

Clinical Investigators' (CIs) Preferences for First-Line Therapy of ALK-Positive Metastatic Non-Small Cell Lung Cancer (IASLC-WCLC 2025) - "Results : For a 60-year-old asymptomatic patient with ALK+ mNSCLC (PD-L1 tumor proportion score [TPS] 0) and no comorbidities, CIs preferred lorlatinib over alectinib as their first-line treatment of choice (80% vs 20%). However, older age and specific preexisting conditions and comorbidities may lead to another treatment approach. Future work is needed to explore current decision-making in these situations for general medical oncologists practicing in a community setting."

Clinical • Metastases • Chronic Kidney Disease • CNS Disorders • Depression • Diabetes • Diabetic Nephropathy • Hypertension • Lung Cancer • Metabolic Disorders • Mood Disorders • Nephrology • Non Small Cell Lung Cancer • Oncology • Psychiatry • Renal Disease • Solid Tumor • ALK • PD-L1

The Effect of a Dutch Breakfast on the Exposure of Alectinib Using a Microtracer Approach: A Proof-Of-Concept Study (IASLC-WCLC 2025) - "Conclusions : These results show that the intake of a Dutch breakfast leads to a delay in absorption of alectinib, and to higher total exposure. Also, this study demonstrated the feasibility of a microtracer food-effect study using a study design with a relatively low patient burden with only two food-controlled drug administrations and a short period of sample collection."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Oral Cancer • Solid Tumor • Thoracic Cancer • ALK

Alectinib as Adjuvant Therapy in Resected ALK-Positive NSCLC: A Prospective Multicenter Cohort Study in China (IASLC-WCLC 2025) - P | "The safety profile of alectinib as an adjuvant treatment in resected ALK-positive NSCLC in routine clinical practice will be evaluated. The study also explores prognostic factors of recurrence, the healthcare utilization before or after the recurrence, the alterations of ALK or other biomarkers identified between the recurrence and initiation of the next anticancer therapy, and treatment options after recurrence."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK