This article describes several hypoxia activated prodrugs including Apaziquone . There you can find a short history of Apaz development, which is not long enough for entire lecture. I would like to hear about the mechanism of Apaz inactivation by blood.
Anti-cancer drugs: trials and tribulations in their development
Wednesday 18 May 2016, 7.00PM
Speaker: Professor Roger Phillips, University of Huddersfield
An evening lecture organised jointly by the Royal Society of Chemistry (Central Yorkshire Section) and the Royal Society of Biology (Yorkshire Branch)
The discovery and development of new anti-cancer drugs is a difficult, time consuming and expensive process. The field is littered with disappointment but these failures provide an opportunity to learn and apply this knowledge to the search for new drugs. This lecture will focus on one such example called EO9 (Apaziquone), a drug that is now in phase III clinical trials for non-muscle invasive bladder cancer despite a history of failure in other clinical trials
Light refreshments will be available from 18.00
Admission: There is no charge for admission or refreshments but prior registration is requested. Further details from Dr Brian Grievson, Department of Chemistry, University of York, Heslington, York, YO10 5DD. Tel: (01904) 324543 e-mail: brian. grievson@york. ac. uk
Wonder if it will be published.
Improving Incentives for the Best Clinical Care
Today, Medicare Part B generally pays physicians and hospital outpatient departments the average sales price of a drug, plus a 6 percent add-on. The proposed model would test whether changing the add-on payment to 2.5 percent plus a flat fee payment of $16.80 per drug per day changes prescribing incentives and leads to improved quality and value. CMS would update the flat fee at the beginning of each year by the percentage increase in the consumer price index for medical care for the most recent 12-month period. This test would begin in late 2016 (no earlier than 60 days after the rule is finalized).
The independent Medicare Payment Advisory Commission (MedPAC) described a similar approach in its June 2015 report to Congress.
CMS expects that the add-on payment of 2.5 percent plus a flat $16.80 fee will cover the cost of any drug paid under Medicare Part B. The flat fee is calculated such that it is budget neutral in aggregate. CMS intends for the test to result in savings through changes in prescribers’ behavior.
Physicians often can choose among several drugs to treat a patient, and the current Medicare Part B drug payment methodology can penalize doctors for selecting lower-cost drugs, even when these drugs are as good or better for patients based on the evidence. To illustrate the effect of this change, consider two drugs each prescribed for a similar condition, with similar patient outcomes, but with widely varying prices. The average sales price for Drug A is $5, and for Drug B it’s $100. Today, Drug A is paid at $0.30 above the price of the drug and Drug B at $6.00. But under this proposal, Medicare would pay Drug A at $16.93 above the average sales price and Drug B at $19.30.
Potentially, it is 25% dilution. It is serious.
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.