Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts tagged ‘crizotinib’

Overcoming drug resistance in lung cancer

On the final day of the annual 2013 meeting of the American Association for Cancer Research (AACR) in Washington DC, Jeffrey Engelman (MGH) hosted an excellent plenary session on “Cancer Evolution and Resistance” with a series of superb talks not only from himself, but also Neal Rosen (MSKCC), Todd Golub (Broad Institute) and René Bernards (Netherlands CI).

If this session is included in the webcast, I would highly recommend watching the whole thing several times, as it was one of the meeting highlights for me. Despite being on the very last day, the large hall was pretty packed and well worth waiting for. You can check availability of the AACR 2013 webcast talks here.

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ASCO 2012 Update 1: Advanced Lung Cancer

ASCO 2012 Outside Arie Crown 300x225 ASCO 2012 Update 1: Advanced Lung CancerIt’s been a crazy busy time since the American Society of Clinical Oncology (ASCO) meeting earlier this month.

This year’s meeting had a lot of hidden gems in both the tumour oral and poster sessions, which will be covered in a series of blog posts.

One theme that clearly emerged was how much effort is being devoted to identifying the causes of acquired resistance to a variety of TKI single agent therapies in order to determine logical combination strategies for the clinic.

Two areas that stood out for their combined translational-clinical efforts at this years ASCO were advanced lung cancer and metastatic melanoma.

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On adaptive mechanisms of crizotinib resistance in ALK-positive lung cancer

One of the biggest challenges facing cancer research was aptly summarised by Levi Garraway and Pasi Jänne in this month’s Cancer Discovery journal:

“All successful cancer therapies are limited by the development of drug resistance. The increase in the understanding of the molecular and biochemical bases of drug efficacy has also facilitated studies elucidating the mechanism(s) of drug resistance.”

It will therefore come as no surprise to PSB readers that resistance occurs with two drugs approved by the FDA only last year; vemurafenib (BRAFV600E melanoma) and crizotinib (ALK+ lung cancer). We’ve discussed the development of resistance in melanoma here via several potential mechanisms in the past and potential strategies for overcoming them (eg MEK inhibitors), but what about lung cancer?

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Combined VEGF and MET inhibition in some cancers may be better than either alone

A couple of recent controversies in the field of angiogenesis have fascinated scientists and clinicians alike, namely:

  • Does VEGF inhibition lead to more aggressive tumours?
  • What drives metastases and invasion?
  • What is the role of tumour hypoxia in this process?

Data was originally presented in glioblastoma by Rubenstein et al., (2000), showing that anti-VEGF antibody treatment prolonged survival, but resulted in increased vascularity caused quite a stir.  Several other groups subsequently demonstrated in preclinical models that VEGF signaling shrinks tumours, but also results in increased invasion and metastases (see Casanovas et al., (2005), Ebos et al., (2009), Paez-Ribes et al., (2009), for examples).

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Update from AACR Molecular Targets 2011 #1 – Breast Cancer

Last week I had an enjoyable time at the AACR-EORTC-NCI Molecular Targets meeting but gippy wifi in San Francisco followed by my blog hosting and RSS feed going haywire meant that reviews of the meeting were delayed until now. There are a couple of interesting topics that emerged during the meeting that I’m going to explore in extended posts this week.

Today’s review looks at new breast cancer data from the conference. There were two things that stood out for me:

  • The role of epigenetics in advanced ER/PR+ breast cancer
  • New potential targets for inflammatory breast cancer (IBC)
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When is NICE is not so nice?

“Ipilimumab is not recommended for the treatment of advanced (unresectable or metastatic) malignant melanoma in people who have received prior therapy.

The Committee was satisfied that ipilimumab meets the criteria for being a life-extending, end-of-life treatment and that the trial evidence presented for this consideration was robust.

The Committee acknowledged that few advances had been made in the treatment of advanced melanoma in recent years and ipilimumab could be considered a significant innovation for a disease with a high unmet clinical need.

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My take on the crizotinib Xalkori FDA approval

Pfizer’s Crizotinib (Xalkori) approved in ALK-positive lung cancer!

The FDA just announced that they have approved Pfizer’s crizotinib (Xalkori):

The U.S. Food and Drug Administration today approved Xalkori (crizotinib) to treat certain patients with late-stage (locally advanced or metastatic), non-small cell lung cancers (NSCLC) who express the abnormal anaplastic lymphoma kinase (ALK) gene.

Xalkori is being approved with a companion diagnostic test that will help determine if a patient has the abnormal ALK gene, a first-of-a-kind genetic test called the Vysis ALK Break Apart FISH Probe Kit. It is the second such targeted therapy approved by the FDA this year.

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The spiralling costs of cancer research and treatment

“The problem at the moment is that it takes $1bn [£600m] to get a drug to market and 15 years or more. That is the justification for the pharmaceutical industry charging high prices.

If on the other hand by the time you get to phase 2 you know exactly which patients it is going to work on, you only put those patients through and instead of 10% you get an 80% response rate.

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Seattle Genetics announce fast track approval of Adcetris

This morning, Seattle Genetics announced that the expected fast track approval from the FDA has been forthcoming for brentuximab vedotin (Adcetris) following the recent unanimous ODAC voting in both refractory Hodgkin Lymphoma (HL) and Anaplastic Large Cell Lymphoma (ALCL).  Clearly, the company and the agency have come to agreement on the confirmatory trials as part of the condition of accelerated review.  The final prescribing information (PI) can be found on the Adcetris website.

For those of you looking for more information on Adcetris, please check out the related posts section below for previous reports on this novel ADC therapy.

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Self-Educated Patients and The Future of Cancer Care

Love this video from TEDxOverlake, where Dr Jack West (Swedish) describes what he is doing with his excellent forum and site, the Global Resource for Advancing Cancer Education (GRACE).  Currently, the main focus is on his specialty, Lung Cancer, but more tumour types are planned in the near future.

Jack talks about how physician led sites can actively and effectively reach out in a many-to-many fashion to improve education and learning, rather than in the traditional one-to-one fashion seen in a consultation.

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