A Phase 1/1b Study Evaluating Trametinib Plus Docetaxel or Pemetrexed in Patients With Advanced Non–Small Cell Lung Cancer

Gandara, David R.; Leighl, Natasha B.; Delord, Jean Pierre; Barlési, Fabrice; Bennouna, Jaafar; Zalcman, G.; Infante, Jeffrey R.; Reckamp, Karen L.; Kelly, Karen; Shepherd, Frances A.; Mazières, Julien; Janků, Filip; Gardner, Olivia S.; Mookerjee, Bijoyesh; Wu, Yuehui; Cox, Donna S.; Schramek, Dan; Peddareddigari, Vijay; Liu, Yuan; D’Amelio, Anthony M.; Blumenschein, George R.

doi:10.1016/j.jtho.2016.11.2218

Cited by 42 publications

(24 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Trametinib, has been evaluated in a phase I trial in combination with docetaxel or pemetrexed in advanced NSCLC patients with or without KRAS mutations [ 17 ]. Both combinations showed activity in KRAS mutant and wild-type tumors.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Implications of KRAS mutations in acquired resistance to treatment in NSCLC

Rofi

Restante

et al. 2017

Oncotarget

View full text Add to dashboard Cite

RationaleKRAS is the most common and, simultaneously, the most ambiguous oncogene implicated in human cancer. Despite KRAS mutations were identified in Non Small Cell Lung Cancers (NSCLCs) more than 20 years ago, selective and specific inhibitors aimed at directly abrogating KRAS activity are not yet available. Nevertheless, many therapeutic approaches have been developed potentially useful to treat NSCLC patients mutated for KRAS and refractory to both standard chemotherapy and targeted therapies.The focus of this review will be to provide an overview of the network related to the intricate molecular KRAS pathways, stressing on preclinical and clinical studies that investigate the predictive value of KRAS mutations in NSCLC patients.Materials and MethodsA bibliographic search of the Medline database was conducted for articles published in English, with the keywords KRAS, KRAS mutations in non-small cell lung cancer, KRAS and tumorigenesis, KRAS and TKIs, KRAS and chemotherapy, KRAS and monoclonal antibody, KRAS and immunotherapy, KRAS and drugs, KRAS and drug resistance.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Different strategies evaluated an epigenetic approach, using cyclin-dependent kinases, heat shock proteins or focal adhesion inhibitors [ 12 – 14 ]. Several researchers wagered on inhibitors of downstream effectors of the KRAS signaling pathways (PI3K/AKT/mTOR and RAF/MEK/ERK) without significant success [ 15 – 17 ].…”

Section: Introductionmentioning

confidence: 99%

Implications of KRAS mutations in acquired resistance to treatment in NSCLC

Rofi

Restante

et al. 2017

Oncotarget

View full text Add to dashboard Cite

show abstract

“…Rash, diarrhea, and peripheral edema were the main adverse events, but those were manageable. A phase I/Ib study evaluating trametinib plus docetaxel or pemetrexed in patients with advanced KRAS-mutant non-small cell lung cancer (NSCLC) showed that the primary endpoint of overall response rate (ORR) was met for both combinations [ 30 ] (ClinicalTrials.gov number, NCT01192165).…”

Section: Mek Inhibitors Approved By the Us Food And Drug Administrmentioning

confidence: 99%

Current Development Status of MEK Inhibitors

2017

View full text Add to dashboard Cite

The current development status of mitogen-activated protein kinase kinase (MEK) inhibitors, including the preclinical data and clinical study progress, has been summarized in this review. Different MEK inhibitors, possessing specific physicochemical properties and bioactivity characteristics, may provide different options for patients seeking treatment for cancer. Moreover, the combination of the MEK inhibitors with other therapies—such as chemotherapy, targeted therapy, and immunotherapy—may be a promising approach for clinical use.

show abstract

“… 43 Trametinib has also been tested in combination with chemotherapy, showing interesting outcomes in an exploratory subpopulation analysis of a phase I study in the subset of patients with G12C KRAS mutations (4 of 10 patients with confirmed response and 8 of 10 with disease control). 44 …”

Section: Targeting Kras In Nsclc Patientsmentioning

confidence: 99%

Treating KRAS-mutant NSCLC: latest evidence and clinical consequences

et al. 2017

View full text Add to dashboard Cite

KRAS mutations represent one of the most prevalent oncogenic driver mutations in non-small cell lung cancer (NSCLC). For many years we have unsuccessfully addressed KRAS mutation as a unique disease. The recent widespread use of comprehensive genomic profiling has identified different subgroups with prognostic implications. Moreover, recent data recognizing the distinct biology and therapeutic vulnerabilities of different KRAS subgroups have allowed us to explore different treatment approaches. Small molecules that selectively inhibit KRAS G12C or use of immune checkpoint inhibitors based on co-mutation status are some examples which anticipate that personalized treatment for this challenging disease is finally on the horizon.

show abstract

A Phase 1/1b Study Evaluating Trametinib Plus Docetaxel or Pemetrexed in Patients With Advanced Non–Small Cell Lung Cancer

Abstract: Trametinib-plus-chemotherapy combinations were tolerable. Clinical activity exceeding the ORRs previously reported with docetaxel or pemetrexed alone in KRAS-mutated NSCLC and meeting prespecified criteria was observed.

Cited by 42 publications

References 30 publications

Implications of KRAS mutations in acquired resistance to treatment in NSCLC

Implications of KRAS mutations in acquired resistance to treatment in NSCLC

Current Development Status of MEK Inhibitors

Treating KRAS-mutant NSCLC: latest evidence and clinical consequences

Contact Info

Product

Resources

About