Overview:
The current approach to decision making about adjuvant chemotherapy results in many patients receiving chemotherapy who do not need it. NICE recommends multi-parameter assay (MPA) use for some node-negative patients. Evidence for MPA use in node-positive disease is weak. Chemotherapy followed by endocrine therapy is still the standard treatment for most of these patients. OPTIMA is a multi-site randomised trial that investigates MPA’s to guide chemotherapy decisions for patients with higher-risk ER-positive HER2-negative early breast cancer.
OPTIMA randomises patients between standard treatment or to have a tumour Prosigna test. Testing is carried out on fixed tissue in a UK-based lab and usually takes less than 2 weeks. Patients with high Prosigna Score tumours (>60) receive standard treatment. Approximately two thirds of patients have a low score tumour and receive endocrine therapy only. Patients allocated chemotherapy are blinded to the reason (randomised to control arm or high Prosigna test score).
View a video about the trial here
Objectives:
- To identify a method of selection that reduces chemotherapy use for patients with hormone sensitive primary breast cancer without detriment to recurrence and survival.
- To establish the cost-effectiveness of test-directed treatment strategies compared to standard practice.
Surgeon Role in OPTIMA
Surgeons are vital for OPTIMA success. Surgeons help identify eligible patients at MDT meetings and have an important role to play in preparing them for discussions about OPTIMA. It is very helpful when referring to adjuvant treatment to avoid adding to or creating an expectation that this will or will not include chemotherapy. We have produced an OPTIMA flyer for surgeons and breast CNS’s to give to eligible patients at their post-surgery appointment. The trial office can supply printed copies of the flyer and an OPTIMA clinic poster.
Practicalities
OPTIMA is a pragmatic study that tries to accommodate local practice and not dictate treatment. It is compatible with many other clinical studies including POSNOC.
OPTIMA is an adjuvant trial but allows pre-surgical endocrine therapy for up to 8 weeks. Post-operative endocrine therapy may be given up to the time of trial treatment allocation.
Secondary cancer surgery such as re-excision of margins or completion mastectomy is permitted following the start of trial treatment including chemotherapy, but all planned axillary surgery must be completed prior to trial entry. Axillary radiotherapy may be given as an alternative to clearance; there is no time limit.
Inclusion Criteria:
- Female or male, age ≥ 40
- Excised invasive breast cancer with local treatment either completed or planned according to trial guidelines. All axillary surgery must be completed before trial entry.
- ER positive (>10% of tumour cells stained positive) and HER2 negative
- Tumour size and axillary lymph node status; one of the following must apply:
i. 4-9 lymph nodes involved AND any tumour size.
ii. 1-3 nodes involved, at least 1 node containing a macrometastasis AND any tumour size.
iii. 1-3 lymph nodes involved with micrometastases only AND invasive tumour size ≥ 20mm.
iv. node negative AND invasive tumour size ≥ 30mm.
- Multiple ipsilateral and clinically “not significant” contralateral cancers are permitted.
Sample Size:
4500 patients (2250 patients per arm) are required to demonstrate non-inferiority of test-directed treatment.
Further Information:
You can find further information about OPTIMA by contacting OPTIMA@warwick.ac.uk and on the trial website including the OPTIMA guide for surgeons and breast CNS's.