May be MEK inhibition in cell lines showed dismal responses but MEK inhibition with selumetinib in KRAS mutation-positive patients demonstrated 37% response rate (vs 0%) and prolonged PFS. Perhaps inhibition of both EGFR and MEK is a better strategy and will be explored in future but Phase 2 data indicate that inhibition of MEK only could be beneficial for patients.
It has a good rationale. Trial's population is KRAS mutation-positive patients. How can you say "No "driver" mutations in the MAPK pathway"? What do you know?
One more abstract
Phase 2 results: encorafenib (ENCO) and cetuximab (CETUX) with or without alpelisib (ALP) in patients with advanced BRAF-mutant colorectal cancer (BRAFm CRC).
He is correct. PFS in a single arm study cannot be used for any approval, including accelerated approval. Marqibo, Folotyn and Belinostat were all approved based on response rates. When you see a response, you know that it is a drug's effect. When you see a PFS curve with no control, what do you know? Placebo will also produce a curve.
I would pay attention to what is going on with Neratinib. Compare titles for Poziotinob and Neratinib trials: "Poziotinib in Patients With HER2+ Recurrent Stage IV BC Who Have Received at Least 2 Prior HER2-directed Regimens" and "A Study of Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer Who Have Received Two or More Prior HER2 Directed Regimens in the Metastatic Setting". Same patient population and Puma runs a 600-patient Phase 3 study with PFS and OS as primary endpoints. I don't see how Spectrum is able to negotiate accelerated approval, especially, if the results of Neratinib trial are positive.
ASH is American Society of Hematology. Why should they accept any abstract on breast cancer? And I don't understand why everybody is so excited about Raj's excitement. He is a specialist in hematologic oncology and does not have any experience in breast cancer and HER inhibitors. We need to hear about how exciting is a new Korean data from more knowledgeable person.
Immunotherapy Puts 93 Percent of Advanced Leukemia Patients in Remission
Friday, 29 Apr 2016 12:20 PM
An astounding 93 percent of patients with advanced leukemia that was resistant to multiple other forms of therapy went into remission after their T-cells were genetically engineered to fight their cancers.
Researchers at Fred Hutchinson Cancer Research Center worked with the University of Washington Cancer Consortium to enroll patients with B-cell acute lymphoblastic leukemia. All of the patients had advanced disease that had relapsed and were immune to other therapies.
The patients received genetically engineered versions of their own T-cells — disease-fighting immune cells — with a synthetic receptor molecule called a CAR (chimeric antigen receptor) that allows T-cells to recognize and kill cancer cells that carry a specific marker called CD19.
T-cells were extracted from patients, and a specialized virus delivered the DNA instructions for making the CAR into the cells. Then, the cells were multiplied to the billions in the lab.
After chemotherapy, the reengineered cells were infused back into the patients they came from about two weeks after they were first extracted.
A few weeks after the infusion, highly sensitive tests could find no trace of cancer in the bone marrow of 27 of 29 patients. CAR T-cells eliminated cancers anywhere in the body they appeared.
Great results, do not bode well for Marqibo.
Read the comment from Barry H Kaplan to this article. It is an oncologist view on Cobi, Cabo and Opdivo. He said that "Opdivo's benefits have been outrageously overstated".
I think that the logic for the second instillation was following: although the difference between placebo and Apaz groups after 90 min was not significant, it was in favor of Apaz. You may need more patients to reach lower p value. It is possible that Apaz works on floating cells better, but it still works on attached cells. Therefore, you may expect an additive effect from two instillations.
Two more abstracts
A phase I study of MEK162 and FOLFOX in chemotherapy-resistant metastatic colorectal cancer.
SELECT-4: Phase I dose escalation trial of selumetinib (AZD6244, ARRY-142886) in combination with durvalumab (MEDI4736) in patients with advanced solid tumors.
Results of NEMO: A phase III trial of binimetinib (BINI) vs dacarbazine (DTIC) in NRAS-mutant cutaneous melanoma.
A Phase I/Ib study of MEK162 (binimetinib), a MEK inhibitor, in combination with carboplatin and pemetrexed in patients with non-squamous NSCLC.
Phase II trial of the MEK1/2 inhibitor selumetinib (AZD6244) in adults with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs).
Phase II Study of the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886) in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN).
Efficacy results of a phase 1b study of ont-380, a CNS-penetrant TKI, in combination with T-DM1 in HER2+ metastatic breast cancer (MBC), including patients (pts) with brain metastases.
Randomized phase II study of AKT blockade with ipatasertib (GDC-0068) and abiraterone (Abi) vs. abi alone in patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel chemotherapy (A. MARTIN Study).
FAIRLANE: A phase II randomized, double-blind, study of the Akt inhibitor ipatasertib (GDC-0068) in combination with paclitaxel as neoadjuvant treatment for early stage triple-negative breast cancer.
A Phase II Basket Study of the Oral TRK Inhibitor LOXO 101 in Adult Subjects with NTRK Fusion-Positive Tumors.
A pediatric phase 1 study of LOXO-101, a highly selective inhibitor of the tropomyosin receptor kinase (TRK) family.
I am not sure what Spectrum needs to do with Folotyn/leucovorin combo. I don't think they keep in mind a phase 3 trial. Most likely, they want to publish data and hope that doctors will use leucovorin off-label.
Two things are important:
1. Seems like leucovorin reduces incidence of mucositis caused by Folotyn. Otherwise why to present?
2. I did not know that Folotyn is used against CTCL. Is it off-label?
Development of novel backbones for the treatment of peripheral T-cell lymphoma (PTCL): The pralatrexate/ romidepsin doublet.
Poster Board: #252
Jennifer Effie Amengual, MD - Presenter
Columbia University Medical Center
Impact of leucovorin on mucositis and skin reactions in pts with peripheral t-cell Lymphoma (PTCL) and cutaneous t-cell lymphoma (CTCL) treated with pralatrexate.
Poster Board: #114
Francine M. Foss, MD - Presenter
Yale Cancer Center