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Philip A. Philip, MD, discusses TTFields, the recent approval of this modality in pancreatic cancer, and phase 3 data in locally advanced disease.
Tumor treating fields (TTFields) are starting to make inroads in the locally advanced pancreatic cancer treatment paradigm and show promise as a new, non-invasive treatment option, according to Philip A. Philip, MD.
“[The PANOVA-3 trial] was positive, significantly improving the long-term survival of patients,” Philip said in an exclusive interview with OncLive®. “[TTFields] also helped in terms of the pain control. Patients who have pain may benefit from this treatment, in addition to the fact that it can potentially prolong their survival.”
In the interview, Philip discussed data from the phase 3 PANOVA-3 trial (NCT03377491), which evaluated TTFields plus gemcitabine and nab-paclitaxel (Abraxane) in patients with locally advanced pancreatic cancer.1 In addition to discussing key data from the trial, like common toxicities seen with the combination, Philip broke down the
Philip is the director of Gastrointestinal Oncology, co-director of the Pancreatic Cancer Center, and medical director of Research and Clinical Care Integration at the Henry Ford Cancer Institute in Detroit, Michigan.
Philip: TTFields are alternating currents that go through the tumor area. [They] have been around for a [long time]. They have been used in brain tumors; that was how [the use of TTFields] started. They’ve also been tested and got approval for use in rare thoracic lung cancers, [including] mesothelioma. More recently, the pancreatic TTFields have been interesting because like radiation treatment, they are not an invasive procedure. [TTFields] don’t involve any surgery; they are [administered] outside of the body. [With TTFields], the patient is wearing the electric fields around their abdomen, covering the area of the tumor where the tumor is seen.
What TTFields do is disrupt the cancer cells and their proliferation. But, in my opinion, [TTFields] go way beyond [disrupting cancer cell proliferation] because they also interfere with the microenvironment. Overall, [TTFields] change the biology of the tumor to a more favorable biology, which controls the growth of the tumor. Also, in a way, by changing the microenvironment, they help the patient symptomatically. That’s what we expect of [TTFields]. [They do not] kill the cancer cells right away or [generate] a major reduction; [rather], this is a gentle way of trying to control the cancer and the environment it sits in.
[TTFields] were known, approved, and used in patients with brain tumors; that was an early read into the proof of concept of this kind of technology. Luckily, it worked, and therefore it was taken to further testing in pancreatic cancer. Locally advanced pancreatic cancer was the [disease setting of the [PANOVA-3] trial that [supported the FDA approval of Optune Pax; this is] an unmet need area where we don’t have good treatments. We use chemotherapy, we use radiation treatment, and here we have another treatment that tends to be well tolerated except for the skin.
TTFields in Locally Advanced Pancreatic Cancer: Take-Home Points
The prospective, randomized trial was undertaken in the United States and in other countries like in Europe. The goal was to look at the benefit of using TTFields in patients. The patients who were selected for this treatment were those who had not received prior chemotherapy or radiation treatment for pancreatic cancer. Most importantly, patients had locally advanced unresectable disease. The primary goal of the treatment and trial was to see whether there was a benefit from this treatment in terms of time to progression of the disease. However, the primary end point was overall survival [OS]. They also collected data on quality of life [QOL] and adverse effects [AEs].
This treatment was given in conjunction with chemotherapy, AEs will appear, but they are not completely due to the TTFields. The main AE due to tumor treating fields was skin toxicity or rash. Skin toxicities are managed by topical treatments to minimize this toxicity. The good thing is, the majority of the patients who had the rash had grade 1 or 2 rash. The grade 3 [skin rash], which was more serious, was seen in [1.8]% of patients.
How [do you] prevent [skin rash from TTFields]? I’m not aware of anything you can do to prevent it as such. Patients who have the skin rash can be treated with a topical application, for example, steroids. Luckily, the majority of patients will not be troubled much by this skin rash.
TTFields are currently used in patients with locally advanced pancreatic cancer that is not resectable; this is the FDA-approved [indication]. In these patients, given the complications we see, [TTFields] is an appropriate treatment. The key thing to remember is that this treatment helps to prolong the life of patients. It’s a treatment that has life-prolonging [qualities] and can improve the QOL of patients. Patients who have unresectable disease and pain are expected to benefit from this treatment, and that would be the exact indication for it and the advantage of giving this treatment.
[In PANOVA-3, TTFields] were given with gemcitabine and nab-paclitaxel. Approximately half of patients [with pancreatic cancer] nowadays receive FOLFIRINOX [leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin]. The question is: Would you also see a benefit adding [TTFields] to FOLFIRINOX? We don’t know.
The other big question relates to the FDA approval of daraxonrasib. The question is: Does combining daraxonrasib with TTFields, with or without chemotherapy, give better results [than either treatment alone]? We don’t know.
Another question [relates to] one of the limitations of this treatment, which is the logistics of patients having to wear it for extended hours every day. Is there evidence that [TTFields treatment durations] can be reduced to only a few hours, which makes it much easier on the patient? That’s something we are eagerly looking forward to [seeing].
These are the questions I would ask in general pertaining to locally advanced pancreatic cancer management, which is the [current] FDA indication [for TTFields]. However, there are situations where we have patients who have metastatic disease, but they have low-volume metastatic disease and not many lesions, especially those who have fewer lung lesions. [These patients do] not technically have locally advanced disease; they have metastatic stage IV disease. Can we use this treatment in those patients also? There are still a lot of questions to expand the indication to beyond locally advanced pancreatic cancer to maybe also patients who have metastatic disease or patients who are older who we cannot do surgery on.
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