Encouraging results for a new mesothelioma chemotherapy

Marianne Baker Posted in Publications 12 April 2017

Other hard-to-treat cancers are now being tested

Encouraging results for a new mesothelioma chemotherapy

To confirm that this promising new treatment is safe through upcoming international trials, the race to recruit people diagnosed with rare cancer types is on.

If you are affected by mesothelioma, other lung cancer, or any type of sarcomatoid cancer (including bladder, kidney, lung, gynaecological tumours), please see the contact details below.

Mesothelioma – a cancer of the lining around the lungs - is a growing problem in the UK, with people exposed to the now banned carcinogenic material asbestos over decades. Until now, treatment options have been limited to one type of chemotherapy, with an average survival time of only 12 months after diagnosis.

A new publication from Dr Peter Szlosarek and his team in the Journal of Clinical Oncology marks the next step in the development of a revolutionary treatment.

Asbestos fibers

The safe dose testing portion of the Phase I clinical trial, called TRAP (Tumours Requiring Arginine to Assess ADI-PEG20 with Pemetrexed and Platinum), revealed unprecedented responses from this small group of patients with cancers no longer responding to current treatments, especially mesothelioma.

Since his PhD research project, Dr Szlosarek has worked on “starving” these relatively rare but aggressive lung tumours of the essential building block that cells need, an amino acid called arginine, in order to halt their growth. He has collaborated with the biotech company Polaris Pharma, who have together developed a drug called ADI-PEG 20 that starves tumours by preventing them from using arginine from the blood to grow.

In the TRAP trial, ADI-PEG20 was combined with the current standard chemotherapy: pemetrexed and cisplatin (pem/cis), or the ADI/Pem/Cis triple combination. The trial ran here at Barts, together with the Guy's, Kings & St Thomas' (GKT) Hospitals, and Cambridge.

This trial follows its predecessor ADAM, which was previously published in JAMA Oncology and awarded our Paper of the Year for 2016.


Why is this exciting?

The results showed a one hundred per cent disease control rate – that is, at least stable disease or the tumours not growing any more at the first assessment scan – including a 78 per cent partial response rate, or tumours actually shrinking.

This is a significant doubling over the usual ~30-40 per cent partial response rate found in similar cancers using current treatments. Importantly, the side-effects were no worse than the pem/cis combination alone.

The trial was run with people who have diagnoses of aggressive mesothelioma including the sarcomatoid type, which has been untreatable until now, showing very limited response to standard chemotherapy before. Part of the improvement was due to a greater response to the pemetrexed drug, as ADI-PEG20 reduced levels of an enzyme targeted by it (Allen et al. 2014).

Where do we go from here?

Dr Peter Szlosarek

These encouraging results feed into the next testing stage for the cancer-starving treatment, a Phase II/III Trial called ATOMIC-meso (ADI-PEG20 targeting of malignancies induces cytotoxicity). Around 150 patients with sarcomatoid or biphasic mesothelioma will enter the Phase II trial, already recruiting in the USA, opening soon in the UK, as well as Australia, South Africa, Taiwan and a number of European countries.

If successful, over 300 patients in total will then be sought for the Phase III trial.

This new treatment plan, having been tested for safe dose levels, is now being expanded to bring in patients with other difficult-to-treat cancers inclduding other types of sarcomatoid cancers (e.g from urological or gynaecological origin).

For a diagnosis that many may not even have heard of before and with such limited treatment options, the possibility of something that arrests the growth of the cancer and may provide precious extra months, the advance is significant.

More encouraging results are expected from the upcoming studies.

We invite anyone living with these cancers, or looking for information for family or friends, to contact our Trial Co-Ordinators by e-mail:

Publication

Phase 1 Dose-Escalation Study of Pegylated Arginine Deiminase, Cisplatin, and Pemetrexed in Patients With Argininosuccinate Synthetase 1–Deficient Thoracic Cancers

Beddowes E, Spicer J, Chan PY, Khadeir R, Corbacho JG, Repana D, Steele JP, Schmid P, Szyszko T, Cook G, Diaz M, Feng X, Johnston A, Thomson J, Sheaff M, Wu B, Bomalaski J, Pacey S, Szlosarek PW. 2017, J Clin Oncol. PMID: 28388291

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