- |||||||||| [VIRTUAL] Optimal Therapeutic Approaches for Patients with Genomic Aberrations beyond EGFR, ALK and ROS1 () - Jun 5, 2021 - Abstract #ASCO2021ASCO_5880;
Not yet recruiting --> Recruiting | Initiation date: Apr 2021 --> Jun 2021 Design, eligibility criteria and key findings from the Phase II VISION trial leading to the recent FDA approval of tepotinib for patients with metastatic NSCLC harboring MET exon 14 skipping alterations Rationale for the design of the ongoing Phase II NAUTIKA1 neoadjuvant and adjuvant study of alectinib, entrectinib, vemurafenib/cobimetinib or pralsetinib for patients with resectable Stage II-III NSCLC harboring ALK, ROS1, NTRK, BRAF V600 or RET molecular alterations Key efficacy and safety outcomes from the Phase II GEOMETRY mono-1 trial supporting the FDA approval of capmatinib for patients with MET exon 14 mutation-positive metastatic NSCLC Practical integration and optimal sequencing of capmatinib and tepotinib into current clinical management of patients with advanced NSCLC harboring MET exon 14 skipping alterations Available safety and efficacy results from the LIBRETTO-001 and ARROW trials leading to the FDA approvals of selpercatinib and pralsetinib for patients with RET fusion-driven NSCLC; optimal integration into clinical practice Design, eligibility and key endpoints of the Phase III LIBRETTO-431 and AcceleRET Lung studies assessing selpercatinib and pralsetinib, respectively, compared to first-line chemotherapy with or without pembrolizumab in patients with treatment-naïve RET fusion-positive advanced NSCLC Frequency and clinical impact of HER2 overexpression or mutations in NSCLC; key efficacy and safety findings from the Phase II DESTINY-Lung01 study evaluating trastuzumab deruxtecan in HER2-overexpressing or mutated NSCLC FDA breakthrough therapy designation and potential nonprotocol role of trastuzumab deruxtecan in patients with HER2-positive metastatic NSCLC Clinical impact of HER3 upregulation as a mechanism of resistance to EGFR tyrosine kinase inhibitors; early efficacy and safety findings with patritumab deruxtecan in a Phase I trial for previously treated patients with EGFR mutation-positive unresectable or metastatic NSCLC Ongoing Phase II HERTHENA-Lung01 trial of patritumab deruxtecan for patients with locally advanced or metastatic EGFR mutation-positive NSCLC who have received prior treatment with osimertinib and at least 1 platinum-based chemotherapy regimen Design, eligibility criteria and key endpoints of the ongoing Phase III GEOMETRY-E trial of capmatinib in combination with osimertinib versus chemotherapy as second-line therapy for patients with locally advanced or metastatic NSCLC harboring non-T790M EGFR activating mutations as well as MET amplification after disease progression on a first/second EGFR tyrosine kinase inhibitor or osimertinib Mechanism of action of sotorasib and available efficacy and safety data from the Phase II CodeBreak 100 trial evaluating sotorasib in patients with previously treated KRAS G12C mutation-positive NSCLC; FDA priority review for sotorasib for KRAS G12C-mutated advanced NSCLC Other ongoing and planned clinical trials investigating novel agents and strategies for patients with advanced NSCLC harboring targetable gene alterations (eg, ECOG-ACRIN LUNG-MAP)
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche
Preclinical, Journal: Combinatorial Therapies to Overcome BRAF/MEK Inhibitors Resistance in Melanoma Cells: An in vitro Study. (Pubmed Central) - Jun 4, 2021
Our results suggest that the combination of MAPK pathway inhibitors with mTOR pathway inhibitors and DCA should be considered as therapeutic options to treat melanoma patients, as the combinations potentiated the effects of each drug alone. In a cell line resistant to vemurafenib, we verified that combined MAPK inhibitors with inhibition of mTOR pathway and/or DCA metabolism modulation might constitute possible strategies in order to overcome resistance to MAPK inhibition.
- |||||||||| Journal: Treatment of hairy cell leukemia. (Pubmed Central) - Jun 3, 2021
High-risk disease including HCL variant and IGHV4-34+ unmutated HCL require further investigation. (197 words).
- |||||||||| Observational data, Retrospective data, Journal, Real-world evidence, IO biomarker: Real-World Experience with Targeted Therapy in BRAF Mutant Advanced Melanoma Patients: Results from a Multicenter Retrospective Observational Study Advanced Melanoma in Russia (Experience) (ADMIRE). (Pubmed Central) - Jun 3, 2021
The median progression-free survival (PFS) and median overall survival (OS) were 9.2 months and 22.6 months, respectively, for the combined first-line therapy; 9.4 months and 16.1 months, respectively, for the combined second-line therapy; and 7.4 months and 17.1 months, respectively, for the combined third- or higher-line therapy. Analysis of treatment patterns demonstrated the effectiveness of the combined TT with BRAF plus MEK inhibitors in patients with brain metastases, rare types of BRAF mutations, and across lines of therapy, as well as a well-tolerated and manageable safety profile.
- |||||||||| glibenclamide / Generic mfg.
Review, Journal: Photosensitizing Medications and Skin Cancer: A Comprehensive Review. (Pubmed Central) - Jun 3, 2021
(4) The research gaps in understanding the relationship between PSMs and skin cancer outlined in this review should be prioritized because the US population is aging. Thus the number of patients prescribed PSMs is likely to continue to rise.
- |||||||||| Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Clinical, Journal: Long-term efficacy of encorafenib plus binimetinib combined treatment: case report. (Pubmed Central) - Jun 2, 2021
Encorafenib plus binimetinib achieved similar efficacy to that observed with previously available combinations, but incidence of some toxicities such as pyrexia and photosensitivity, which have a relevant impact on patients quality of life, is lower. In this article, the case of a patient who received encorafenib and binimetinib within the phase 3 trial COLUMBUS is presented and discussed, with a focus on the clinical management during the pandemic caused by SARS-CoV-2 virus.
- |||||||||| Qinlock (ripretinib) / Deciphera
[VIRTUAL] Dermatopathological review of cutaneous squamous cell carcinoma events in patients with gastrointestinal stromal tumors treated with ripretinib () - Jun 1, 2021 - Abstract #ESMOGI2021ESMO_GI_260;
P1, P3
Background Ripretinib, a broad-spectrum KIT and PDGFRA switch-control tyrosine kinase inhibitor (TKI), is indicated for patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib...The incidence of all-grade cutaneous squamous cell carcinoma (cuSCC) with BRAF inhibitors, vemurafenib and dabrafenib, was 12.5% in a meta-analysis of 6,445 patients from 21 studies...The cuSCC lesions did not show aggressive histopathological features and were analogous to their lowest-risk ultraviolet-induced counterparts. Thus, the cuSCC lesions in patients treated with ripretinib can generally be managed using local interventions, without the need for dosing modifications or interruptions.
- |||||||||| Germanin (suramin) / Optimum Therap, Zelboraf (vemurafenib) / Roche
Review, Journal: Structure and function of USP5: Insight into physiological and pathophysiological roles. (Pubmed Central) - Jun 1, 2021
In the present review, we focus on USP5 and provide a comprehensive overview of the current knowledge regarding its structure, physiological roles in multiple cellular events, and pathophysiological roles in relevant diseases, especially cancer. Signaling pathways and emerging pharmacological profiles of USP5 are also introduced, which fully embody the therapeutic potential of USP5 for human diseases ranging from cancer to neurological diseases.
- |||||||||| Review, Journal: Management of toxicities of BRAF inhibitors and MEK inhibitors in advanced melanoma (Pubmed Central) - May 28, 2021
This paper summarizes tolerance data from the three pivotal trials (coBRIM, COMBI-v and COLUMBUS) and issues recommendations for the specific management of main toxicities, based on experts' opinion. We discuss dermatological, ophthalmological, cardiovascular, digestive, musculoskeletal, renal and general toxicities and propose a timetable for examinations to be performed before and during treatment.
- |||||||||| Zelboraf (vemurafenib) / Roche
Trial completion date, Trial primary completion date: BRAF Inhibitor, Vemurafenib, in Patients With Relapsed or Refractory Hairy Cell Leukemia (clinicaltrials.gov) - May 27, 2021
P2, N=36, Active, not recruiting,
We discuss dermatological, ophthalmological, cardiovascular, digestive, musculoskeletal, renal and general toxicities and propose a timetable for examinations to be performed before and during treatment. Trial completion date: Oct 2021 --> Oct 2022 | Trial primary completion date: Oct 2021 --> Oct 2022
- |||||||||| Mekinist (trametinib) / Novartis, Tafinlar (dabrafenib) / Novartis
Clinical, Journal: Comparative efficacy of dabrafenib + trametinib versus treatment options for metastatic melanoma in first-line settings. (Pubmed Central) - May 25, 2021
The network meta-analysis results suggested that dabrafenib + trametinib significantly prolongs the survival outcomes compared with the monotherapies and had comparable efficacy profile compared with encorafenib + binimetinib and cobimetinib + vemurafenib. In comparison with immunotherapies, the results varied for progression-free survival and overall survival. Long-term survival data of dabrafenib + trametinib establishes the combination as one of the preferred treatment options for previously untreated melanoma patients.
- |||||||||| Mekinist (trametinib) / Novartis, Zelboraf (vemurafenib) / Roche
Clinical, Journal: Methiothepin Increases Chemotherapy Efficacy against Resistant Melanoma Cells. (Pubmed Central) - May 25, 2021
We previously reported that methiothepin, a small molecule known as a nonselective serotonin 5-HT receptor antagonist, inhibited the doxorubicin efflux activity of the Hedgehog receptor Ptch1 and enhanced the cytotoxic, pro-apoptotic, anti-proliferative, and anti-clonogenic effects of doxorubicin on adrenocortical carcinoma cells...Melanoma patients having the BRAF mutation are treated with vemurafenib, an inhibitor of BRAF, often in combination with trametinib, an inhibitor of MEK...We observe that the addition of methiothepin to vemurafenib prevents migration of resistant melanoma cells more efficiently than vemurafenib alone. Our results provide an additional proof that Ptch1 drug efflux inhibition increases the effectiveness of anti-cancer treatments and overcomes resistance of melanoma cells expressing Ptch1.
- |||||||||| Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche, Zelboraf (vemurafenib) / Roche
Journal: Durable Responses with Vemurafenib plus Rituximab in Hairy-Cell Leukemia. (Pubmed Central) - May 23, 2021
Our results provide an additional proof that Ptch1 drug efflux inhibition increases the effectiveness of anti-cancer treatments and overcomes resistance of melanoma cells expressing Ptch1. Of 30 patients with relapsed or refractory hairy-cell leukemia, 87% experienced complete responses.
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche, Tecentriq (atezolizumab) / Roche
Enrollment open: Tricotel: A Study Evaluating the Safety and Efficacy of Cobimetinib Plus Atezolizumab in BRAFV600 Wild-type Melanoma With Central Nervous System Metastases and Cobimetinib Plus Atezolizumab and Vemurafenib in BRAFV600 Mutation-positive Melanoma With Central Nervous System Metastases (clinicaltrials.gov) - May 18, 2021
P2, N=120, Recruiting,
We established a framework to systematically identify crucial factors responsible for marginal survival effects, analyzed mechanisms underlying marginal effects, and identified related drugs. Active, not recruiting --> Recruiting
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS
Retrospective data, Review, Clinical Trial,Phase I, Clinical Trial,Phase II, Journal: Adjuvant therapy for cutaneous melanoma: a systematic review and network meta-analysis of new therapies. (Pubmed Central) - May 15, 2021
Concerning AEs, pembrolizumab and nivolumab showed the highest probability to be less associated with any and 3-4 grade AEs (83.1% and 64.4%, respectively). In conclusion, all new drugs are highly effective in adjuvant setting and the best choice is dependent of patient's context.
- |||||||||| Nexavar (sorafenib) / Bayer, Amgen
Preclinical, Journal: Differential responsiveness to BRAF inhibitors of melanoma cell lines BRAF V600E-mutated. (Pubmed Central) - May 15, 2021
In conclusion, all new drugs are highly effective in adjuvant setting and the best choice is dependent of patient's context. Cell lines carrying V600E mutation at the DNA level may respond differently to BRAF targeted treatment potentially due to a lower V600E RNA expression.
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche
Biomarker, Retrospective data, Journal, IO biomarker: Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib ± cobimetinib: a pooled analysis of four clinical trials. (Pubmed Central) - May 15, 2021
P1, P2, P3
ppRx with immunotherapy or targeted therapy is an independent prognostic factor for improved overall survival following progression regardless of original treatment. Trial registration The trials included in this analysis are registered with ClinicalTrials.gov: NCT00949702 (BRIM-2), NCT01006980 (BRIM-3), NCT01271803 (BRIM-7), and NCT01689519 (coBRIM).
- |||||||||| imatinib / Generic mfg.
Clinical, Review, Journal, Checkpoint inhibition: Neuromuscular complications following targeted therapy in cancer patients: beyond the immune checkpoint inhibitors. Case reports and review of the literature. (Pubmed Central) - May 15, 2021
The first patient was treated with the combination of Vemurafenib and Cobimetinib, BRAF and MEK inhibitors, respectively, for a cutaneous melanoma...The second patient received therapy with Imatinib, tyrosine kinase inhibitor and precursor of the targeted therapy, for a gastrointestinal stromal tumour...DISCUSSION AND We strengthen the relevance of neuromuscular complications which may occur long after treatment start or in patients receiving not only the latest ICPi but also "older" and apparently better-known targeted therapies. Also in the latter cases, an immune-mediated "off-target" pathogenic mechanism can be hypothesized, and consequences can be life threatening, if not promptly diagnosed and appropriately managed.
- |||||||||| Tafinlar (dabrafenib) / Novartis
Clinical, Journal: Dabrafenib-induced neutrophilic panniculitis in a child undergoing dual BRAF-MEK inhibitor therapy for glioblastoma multiforme. (Pubmed Central) - May 15, 2021
We report a case of dabrafenib-induced neutrophilic panniculitis in a 9-year-old girl that manifested within several weeks of initiating dual BRAF-MEK inhibitor therapy for glioblastoma multiforme. This case highlights neutrophilic panniculitis as a side effect of dabrafenib in children and serves as a reminder to consider cutaneous side effects of BRAF inhibitors as they are increasingly used to treat children with primary brain tumors.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Proteomics pipeline for phosphoenrichment and its application on a human melanoma cell model. (Pubmed Central) - May 15, 2021
In fact, each methodology permits to identify only a fraction of the phosphoproteome contained in a whole cell lysate. The selection of the most efficient protocols and a combination of two phospho-enrichment methods allowed the assessment of this workflow able to pinpoint the main actors in the phospho-proteome cascade of A375 human melanoma cells treated with Vemurafenib.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal, IO biomarker: A20 promotes melanoma progression via the activation of Akt pathway. (Pubmed Central) - May 14, 2021
What's more, the up-regulation of A20 conferred the acquired resistance to Vemurafenib in BRAF-mutant melanoma. Taken together, we demonstrated that up-regulated A20 promoted melanoma progression via the activation of Akt pathway, and that A20 could be exploited as a potential therapeutic target for melanoma treatment.
- |||||||||| PLX8394 / Novellus, Zelboraf (vemurafenib) / Roche
Journal: Novel and Potent Small Molecules against Melanoma Harboring BRAF Class I/II/III Mutants for Overcoming Drug Resistance. (Pubmed Central) - May 13, 2021
Moreover, SIJ1777 substantially inhibits the activation of MEK, ERK, and AKT and remarkably induces apoptosis and significantly blocks migration, invasion, and anchorage-independent growth of melanoma cells harboring BRAF class I/II/II mutations while both vemurafenib and PLX8394 have little to no effects on melanoma cells expressing BRAF class II/III mutations. Taken together, our six GNF-7 derivatives exhibit highly potent activities against melanoma cells harboring class I/II/III BRAF mutations compared with vemurafenib as well as PLX8394.
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