2-THE-TOP in Name and in Facts

Normally these news are reported in the articles where I summarize every two months the most relevant results of the research on glioblastoma, but the results are so good that have convinced me to immediately write something.

Let’s get to the point. These are the preliminary results of the 2-THE-TOP clinical trial using the Optune device combined with Pembrolizumab (Keytruda) and Temozolomide on newly diagnosed Glioblastoma patients.

Well, patients in the phase 2 clinical trial achieved a median progression-free survival of 12.1 months compared to 7.9 months in study EF-14.

Patients in the 2-THE-TOP achieved a median overall survival of 25.2 months, compared with 15.9 months for patients in the control group of study EF-14.

Of the 15 patients involved in the 2-THE-TOP study with measurable target lesions, six (40%) achieved a partial to complete response and eight (53%) achieved stable disease stabilization.

These results are exciting and confirm to the potential benefit of combined treatment with tutor treating fields, pembrolizumab and temozolomide and confirm the ability of the Optune device to activate an immune response, effectively transforming a cold (for the immune system) tumor into a warm tomour, i.e. attackable by the immune system which is stimulated by drugs such as Keytruda.

The 2-THE-TOP study is a Phase 2 – The study is designed to evaluate the efficacy and tolerability of using the Optune device together with pembrozumab and temozolomide for the treatment of newly diagnosed adult GBM patients. Patients enrolled in the study underwent maximal tumor resection followed by standard chemoradiotherapy. After completion of chemoradiotherapy, patients began a series of monthly cycles of adjuvant temozolomide. Treatment with the Optune device began approximately at the same time as the first cycle of adjuvant temozolomide. Pembrolizumab was introduced in the second cycle of treatment and subsequent cycles of pembrolizumab were given every three weeks until disease progression or risk of unacceptable toxicity or 2 years after the beginning of the treatment.

The reference EF-14 study was a large randomized Phase 3 study that compared treatment with the Optune device combined with temozolomide versus temozolomide alone in the treatment of newly diagnosed glioblastoma after radiotherapy. Median progression-free survival was 6.7 months for combined treatment compared with 4 months for temzolomide alone. Median overall survival was 20.9 months for combined treatment compared with 16 months for temozolomide alone (STUPP).

So let’s make some considerations. The first is that the solution to glioblastoma can only come from a synergistic combination of different treatments. The second is the effectiveness of using the Optune device in combination with other treatments.

We come now to the bad news. The Optune device is not part of the standard treatment proposed in Italy and it seems to be increasingly difficult to obtain. The device is very expensive, requires the patient to shave to zero and must be worn for at least 18 hours a day. Including the battery the device weighs a couple of kilograms. However, several studies have shown its effectiveness, so we should make an attempt to offer it as an optional treatment funded by the national system and allow patients to choose whether to use it or not by comparing positive and negative effects.

Finally, allow me a final thought. If all the money spent on war operations in these weeks were used for research … who knows what final results will be obtained … for sure it will give us more chances to defeat this terrible disease within a few years.