It sure looks to me that Cobi has it going on. Makes me wonder how many other trials with good results that Cobi may be part of. Nobody seems to be bringing it our attention for some reason. GL.
Adopted at the CHMP meeting of 17-20 November 2014
Cometriq (cabozantinib s-malate)
TMC Pharma Services Ltd
Recommending renewal of conditional Market Authorisation
Abstractmportance Eruptive melanocytic nevi (EMN) are characterized by the sudden onset of numerous melanocytic nevi and have been traditionally described in the setting of immunosuppression. Selective BRAF inhibitors such as vemurafenib cause multiple cutaneous adverse effects, including the formation of cutaneous squamous cell carcinoma, as well as EMN. We describe the first reported case, to our knowledge, of involution of BRAF inhibitor–induced EMN following the concomitant addition of a MEK inhibitor, cobimetinib.
Observations A woman in her 20s with a history of metastatic melanoma developed EMN while receiving therapy with vemurafenib, a selective BRAF inhibitor. After disease progression, the patient was placed on a clinical trial that combined vemurafenib with a MEK inhibitor, cobimetinib. Within months, we noted clinical involution of many of her EMN. In addition, numerous preexisting nevi were noted to fade in color on the dual regimen. Over a year after initiating this combination therapy, most of the patient’s EMN were no longer clinically evident.
Conclusions and Relevance Our case report describing the involution of EMN supports data from previous clinical trials indicating that combination BRAF and MEK inhibition may reduce cutaneous proliferative effects that arise on BRAF inhibitor monotherapy. Further studies are necessary to characterize the biological mechanisms underlying this phenomenon.
JAMA Dermatol. 2014 Nov 26. doi: 10.1001/jamadermatol.2014.2734. [Epub ahead of print]
go to pubmed and search for Cabozantinib
As much as it is news of toxic reactions by patients, I think they would decide to handle them if they were suffering from cancer. No big deal on this report.
Sentiment: Strong Sell
Please post the reference and date of publication/announcement. Thanks
Sentiment: Strong Buy
If I am reading the Results correctly this doesn't appear to be very good news.
Cabozantinib for Malignant Pheochromocytoma
Sponsor: M.D. Anderson Cancer Center
First received: November 21, 2014
Last updated: November 24, 2014
Cabozantinib S-malate is a vascular endothelial growth factor receptor 2, c-MET, and RET multitargeted tyrosine kinase inhibitor that has antiangiogenic and antitumorigenic properties with potential efficacy for the treatment of several cancers. Cutaneous reactions, one of the most frequently observed adverse effects associated with tyrosine kinase inhibitors, can significantly affect patients' quality of life and drug adherence and represent a major therapeutic challenge to maximizing the efficacy of targeted cancer therapy.
To describe the frequency and spectrum of skin reactions in patients with urothelial carcinoma receiving cabozantinib as monotherapy.
Design, Setting, and Participants:
A single-institution study at the Clinical Research Center at the National Institutes of Health included 41 consecutive adults with metastatic, progressive urothelial carcinoma enrolled in a National Cancer Institute open-label, nonrandomized, phase 2 clinical trial. Patients receiving cabozantinib were evaluated for the development of skin reactions at each treatment visit from October 2012 to June 2014 by the primary oncology team and referred for dermatologic evaluation as appropriate.
Main Outcomes and Measures:
A detailed history, full-body physical examination, and clinical photographs of cutaneous lesions were obtained.
Of 41 consecutive patients who received cabozantinib, 30 (73%) developed 1 or more cutaneous toxic effects. Adverse events included hand-foot skin reaction (22 [54%]), generalized pigment dilution and/or hair depigmentation (18 [44%]), xerosis (8 [20%]), scrotal erythema/ulceration (6 [15%]), and nail splinter hemorrhages (5 [12%]). Eighteen patients (44%) had 2 or more cutaneous adverse events. Re
PDL1 + XL888 + MEK162
By specific IT, NRAS mutation predicted benefit compared to WT/WT for anti-PD-1/PD-L1 (RR 78% vs. 19%, p=0.002; CBR 78% vs. 29%, p=0.013, n=30) and ipi (RR 18% vs. 12%, p=0.315; CBR 41% vs. 22%, p=0.018, n=137). No significant differences were observed with IL-2 (RR 33% vs. 28%, p=0.730; CBR 33% vs. 39%, p=0.741, n=33)
P1b PDL1 + V
P1b PDL1 +V +COBI
IV fixed at either 15 or 20 mg/kg every 3 weeks (q3w), or a fixed dose of either 1200 mg q3w, or 800 mg every 2 weeks (q2w), depending on the arm/cohort.
Drug: Vemurafenib (Zelboraf®)
Oral repeating dose
Oral repeating dose
I see the " results are long overdue " as a good thing. I believe it had something to do with the way it traded today. Happy Turkey Day everybody!!