AstraZeneca’s PARP inhibitor olaparib prolonged remission in serous ovarian cancer
Last week the American Society of Clinical Oncology (ASCO) held a press briefing to highlight some of the studies at the forthcoming annual meeting in Chicago next month.
ASCO president, Dr George Sledge of Indiana, announced that the meeting theme for this year is “Patients, Pathways, Progress” to reflect the growing focus on molecular targets to identify and treat patients more effectively.
Traditionally, ASCO has organised their meeting around tumour types such as breast, lung, prostate and colon cancers, for example, but this year I was delighted to see that the Developmental Therapeutics section is getting more attention with a greater focus on the molecular targets that are now emerging:
Of the abstracts covered in the briefing, two in particular really stood out for me. One was on Exelixis’ cabozantinib (XL184) in bone metastases, which my colleague wrote about on Biotech Strategy Blog and the other was the data for AstraZeneca’s PARP inhibitor, olaparib, in serous ovarian cancer.
Many of you will know that I’ve been covering PARP inhibitors on this blog since 2006 – although they have had somewhat of a chequered history to date. After the recent failure of Sanofi’s iniparib in triple negative breast cancer and AstraZeneca deciding to put a phase III breast cancer trial on hold while they reformulate the drug from capsules to a tablet to make it easier for people to take, many weren’t sure what was happening with the PARP class of compounds.
Would they be consigned to the drug dustbin or would they come back from the dead?
Dr Jonathan Ledermann (University College London) presented an overview of the phase II results in serous ovarian cancer. These were women both with, and without, the BRCA gene. It has previously been shown by Audeh et al., (2010) that ~30% of inherited BRCA mutated tumours respond to PARP inhibitors, particularly those that have ‘platinum-sensitive’ disease.
Here is the phase II study design in serous ovarian cancer:
What was in interesting in this study was that, overall, Dr Ledermann noted that they found that women in the olaparib arm lived for 8.4 months before progression, compared to 4.8 months on placebo. This 3.6 month improvement in PFS was statistically significant.
We will know more about the details of this study on Saturday 4th June at ASCO, but for now, two things stand out:
- This is the first study to demonstrate a statistically significant benefit of maintenance treatment for ‘platinum-sensitive’ relapsed serous ovarian cancer
- 50% of olaparib and 16% of placebo patients were still on treatment at the time of the analysis
These results seem pretty compelling and important to me.
If you’re around at ASCO on Saturday, the ovarian cancer session is on from 3-6pm in room E354a – check it out!
For those interested, there are also some new data being presented on Abbott’s PARP inhibitor, ABT-888 (veliparib) combined with temozolomide in refractory colorectal cancer. This is also on Saturday afternoon from 4.30-6pm in the Clinical Science Symposium in Hall D1.
No doubt many of us will be running around up and down the escalators on the very first day, some Segways with hooters might help! Still, I dream/long for the future when ASCO follows AACR’s lead and organises sessions around molecular targets and pathways instead of tumour types… maybe that won’t be too far into the future after all 🙂
References:
Audeh, M., Carmichael, J., Penson, R., Friedlander, M., Powell, B., Bell-McGuinn, K., Scott, C., Weitzel, J., Oaknin, A., Loman, N., Lu, K., Schmutzler, R., Matulonis, U., Wickens, M., & Tutt, A. (2010). Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial The Lancet, 376 (9737), 245-251 DOI: 10.1016/S0140-6736(10)60893-8
5 Responses to “AstraZeneca’s PARP inhibitor olaparib prolonged remission in serous ovarian cancer”
I am not sure I agree with your desire to be molecular target and pathway focused at ASCO. After all, ASCO is aimed at clinicians, and as I treat only breast cancer patients, I only go to the breast sessions. Also, my feeling that the pathways will be tissue specific, so whilst AACR is target/ pathway focussed as it is about basic science and this is great for my Pi3K addiction, cancer treatment may still be related to site of origin…
Ah, I knew someone was going to say that. My response would be that there are tumour specialty meetings for that eg SABCS, ASCO GU, ASGO GI.
The challenge is that not all clinicians specialise in one cancer, unless they are in academia. The majority of oncologists in private practice in the US, for example, will see most tumour types and don’t specialise at all.
What they want to know is what’s new and hot data across the board. Therefore, they end up running around like me, from session to session, trying to catch the things that most interest them. Few will sit through a whole session of old data when there’s something new in another parallel session. That’s why a huge number of people suddenly get up and leave after new data and head off to a different room. I’m not the only one doing this.
It’s a crazy world where a huge number of people are running around across 4 halls in Chicago because the schedule forces them to… there’s nothing worse than wasting valuable time crossing that long bridge a dozen times a day 🙁
But, as you said yourself, the same targets and pathways aren’t all relevant across tumor types. So people would stick around for the BRAF V600 session just long enough to see the melanoma presentations and then cut out before the CRC ones in order to go catch the EGFR/MET stuff on the other side of the bridge. I know PARPi/DNA repair feels different right now, but by the time it hits the clinic it’ll have its dead spots too. And I think if they’re going to cater to the community oncologist at all then they’ve got to leave it by tumor type for now.
I don’t envy you, though! I cover landscape in only 6 indications and I am eyebrow-deep in tough choices.
Fair point, but I think a lot of people would be very interested, for example, in all the BRAF V600E inhibitors, since there is data on vemurafenib, RAF265 and the GSK long whatever number it is (can never remember it!). You could at least get a better sense of that class of inhibitors in melanoma as a community physician.
The same would go for the PARP inhibitors since there is data on olaparib and iniparib in ovarian cancer and veliparib in colon cancer.
It’s unlikely to happen until there are more physician-scientists focused on ‘pathwayness’ overwhelming the specialists, so of course, I am dreaming. We need some Star Trek transponders in the meantime 🙂
That said, if we truly want to speed better drugs to market in smarter, iterative, better designed phase II trials, we have to be prepared to make changes. The current approach hinders rather than helps new product development and clinical development.
In the long run, what’s the best thing for patients?
It is very encouraging to see that the parp inhibitor drug may be used to treat a wide variety of cancers. Small trials were very encouraging and they are now undertaking bigger trials, I am looking forward to seeing the results!
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