What does the Future Hold for Stomach, Lung, and Testicular Cancer Treatments?

Cancer is a leading cause of death worldwide. Despite the lack of a definitive cure for cancer, there are many types of cancer treatments. A patient’s treatment depends on the type and stage of cancer they have. It varies from one type to several, including surgery, chemotherapy, radiation therapy, immunotherapy, and targeted therapy.

Key Highlights

The month of November marks multiple cancer awareness events, namely for testicular cancer, lung cancer, and stomach cancer. To gain more insight into the current and future treatment paradigm for these cancers, we spoke to Thomas Ng, Senior Medical Director—Medical Affairs.

Tweet
Samantha Mineroff
Samantha Mineroff
Copywriter
Nick Tate
Nick Tate
Copywriter

Some patients may participate in clinical trials when there is no available treatment option, or the patients may not be able to tolerate standard treatment. These trials can often represent their last chance of remission or a reprieve from the advancing disease.

Cancer patients have an overwhelming amount of information to learn and to absorb, which can leave them feeling confused and exhausted. But talking to a doctor is the first step that can set them on a road to the right treatment for their cancer.

The month of November is used by numerous cancer patient advocacy groups to highlight cancer awareness, namely for testicular cancer, lung cancer, and stomach cancer. To gain more insight into the current and future treatment paradigm for these cancers, we spoke to Thomas Ng, Senior Medical Director—Medical Affairs.

Tell us about your background and experience in oncology research and medicine. Tell us also about PRA's expertise in this field with reference specifically to immuno-oncology, lung, testicular, and stomach cancers.

I’ve been working in clinical research within the pharmaceutical industry for 20 years. My primary focus is on hematology and oncology (both solid tumors and blood malignancies). I have been involved in clinical development of a broad spectrum of oncology products, with experience including new chemical entities, biological agents, vaccines, biosimilars, and advanced therapy medicinal products. While working at PRA over the last eight years, I have been providing medical oversight and medical monitoring activities on oncology clinical trials, with some of these trials focusing on lung cancer, stomach cancer, and testicular cancer.

At PRA, we have more than 50 oncologists and haemato-oncologists working globally and have experienced in managing oncology clinical trials. Over the last five years, PRA has been involved in more than 200 oncology clinical trials, with a significant proportion of these trials as part of cancer assessment or solely involved, in lung cancers, stomach cancers, and testicular cancers. Quite a few of the investigational medicines of these oncology trials utilizes the patient’s own immune system to help fighting against cancers through various mechanisms, a key principle of immune-oncology research.

It’s important to note lung cancer is the most common cancer in men while it is the third most common cancer in women. The most common subtype of lung cancer is non-small cell lung cancer (NSCLC) in which clinical trials have been widely focused. Stomach cancer is the fifth common cancer worldwide, with adenocarcinoma being the most common subtype. Although testicular cancer represents only about one percent of male cancer, it is common in young men in the western world. The most common subtype of testicular cancer is of germ cell origin.

Over the last 10 years, oncology clinical trials have been increasingly focused on immuno-oncology, assessing treatment benefits by using target antibodies, immunomodulators like checkpoint inhibitors (CPIs), T-cell therapy, and cancer vaccines. Various target antibodies and CPIs have been approved for treatment of lung cancer as single drug or combined with chemotherapy to treat NSCLC.

Although testicular germ cell cancers generally have a good prognosis (up to 90 percent survival rate over 10 years), a significant proportion of patients will subsequently relapse. Those who fail to respond to standard platinum-based or salvage chemotherapy carry a poor prognosis. Exploration of various treatment modalities, especially CPI, in the treatment of testicular germ cell cancers have been active over the last five years.

Can you tell us about the most impactful research advancements of the past few years (for cancer prevention, molecular diagnostics, and cancer treatment)?

From a clinical research perspective, a lot of focus has been on genetic mutation (as a biomarker) of cancer. The assessment of some of these biomarkers are now part of a standard of care. In terms of how this has been applied to the various cancers we’re speaking about here, for lung cancer, the testing of a panel of biomarkers including specific biomarkers used to detect genetic mutations or their products: epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), proto-oncogene 1, receptor tyrosine kinase (ROS1), and Kristen ras oncogene (KRAS). These allow a medical team to determine the best treatment for the patients.

For stomach cancer, a genetic mutation(s), such as human epidermal receptor growth factor receptor-2 (HER-2), can cause an over-expression of the cancer protein. This leads to the use of targeted therapy to treat the cancer.

Another key development has been the targeting of therapies to provide maximum clinical benefit to the sub-group of cancer patients. The use of a targeted therapy could potentially limit the unselected side effects of traditional chemotherapy and radiotherapy.

That said, the exploration of biomarkers to guide the development of new treatments will provide the maximum benefits to cancer patients suffering a specific genetic mutation.

Can you tell us what the cancer research priorities are to accelerate progress against cancer (with reference specifically to stomach, lung, and testicular)?

In general, focusing on current unmet medical needs is important. It’s especially critical for patients who failed on standard and salvage—aka, “rescued,” providing treatment after standard therapy has failed—treatment and patients who either couldn’t receive standard treatment or there is no further therapeutic option.

A priority for researchers is to figure out the cause of cancer being resistant and refractory to treatment. The treatment issue—the treatment resistance and refractory—is not just from the cancer cells, but also related to the interaction between cancer cells and surrounding cells and tissues, so called the tumor micro-environment, based on our understanding of how CPI works.

We also must consider how to improve survival of patients without compromising quality of life. A huge milestone in cancer treatment is the use of CPI for the treatment of advanced malignant melanoma. At that time, there was only one treatment which showed a significant improvement of overall survival when compared to traditional treatment in advanced malignant melanoma.

Another key development is the use of CAR-T therapy. By genetically modifying the patient’s own T-cell, an artificial T-cell receptor is produced, which could effectively attack the cancer cells. CAR-T therapy has been approved in the treatment of ALL of children and young adults who failed to respond to treatment, and in adults with relapsed and refractory DLBCL and MCL. By translating the scientific understanding and the potential benefits, inroads are being made on these treatment approaches. There are active clinical trials investigating the treatment benefits of CPI (either alone or coupled with standard treatment) and CAR-T therapy in lung, stomach, and testicular germ cell cancers. We’re eagerly awaiting the results of these trials

Learn more about the use of CAR-T Cell Therapies in Hemato-Oncology

Do you have any insights into the use of CRISPR, CAR-T, or genome editing to treat rare forms of cancer and indeed those of the stomach, lung, and testicle?

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is a segment of DNA containing short repetitions of base sequences.

By using the CRISPR sequence of DNA and its associated proteins, researchers could selectively modify the function of targeted cells’ genes. Such technology, known as gene editing, has been in intense development since 2012, initially as a rapid diagnostic tool. Gene editing principles have recently been applied in various cancers. These applications are an attempt to manage patients who failed standard treatment or have no treatment options available.

Learn more about CRISPR’s potential for patients with devastating diseases.

For stomach cancer, there are at least two active studies using modified T-cells in which particular genes on immune checkpoints are inactivated. For lung and testicular cancers, such technological evaluation needs to be further explored.

Another gene editing tool involves the modification of a T-cell’s function. This is called Chimeric Antigen Receptor T (CAR-T) cells. It works to re-program the T-cell function via a complex ex-vivo process, so that the re-engineered T-cells are more effective in killing cancer cells based on a specific cancer antigen. The technology of CAR-T was initially developed in 1989-1993 but it took another 8 years before clinical trials on patients in 2011. Four generations of CAR-T have been described, based on the improvement of anti-cancer activity of T-cells and its prolonged T-cells lifespan. CAR-T therapy has already been approved in the treatment of three types of blood cancers which failed to treatment: B-cell acute lymphocytic leukaemia (ALL) in 2017, diffuse large B-cell Lymphoma (DLBCL) in 2017, and mantle cell lymphoma (MCL) in 2020. Further modification of CAR-T cells to improve treatment safety and cancer killing activity has been actively investigated. There are currently more than six active trials involving CAR-T therapy focusing on advanced stomach and lung (NSCLC) cancers with/without CPI and chemotherapy.

Inclusion criteria for patient enrollment for oncology trials has changed a lot over the years. For example, almost any affected patient could enroll, but now there's specific criteria that dictate who can take part, lowering the percentage of patients in oncology trials on the whole. Can you speak to the benefits of these changes for the patient, including the standard of care and the use of specific targeted therapies?

In the early days of medicine, researchers tried to find treatments that could meet the “one-size-fits-all” principle. Traditional cancer treatment using chemotherapy and radiotherapy has shown that not all cancer patients respond to the treatment.

Furthermore, patients who responded had variable durations of treatment benefit. One big reason for this is that during treatment, both healthy and cancer cells are destroyed. Current oncology research trends focus on a subset population whose target therapy would produce the maximum benefit in terms of response and survival, with an acceptable safety treatment profile.

Some tumors express themselves through a particular mutation. If we can optimize our treatment by using a therapy that targets that particular mutation, we would expect optimal benefit of treatment in terms of the effect of killing off the tumor and reducing the damage to the surrounding healthy cells. Target therapy has demonstrated significant improvement in terms of treatment response and survival when compared to chemotherapy, which was previously considered as a standard treatment.

What are your thoughts on the global impact that the RACE Act, which is new US legislation specific to pediatric oncology trials, will have on oncology trials?

The RACE Act has requested pharmaceutical companies to examine the mechanism of action, not just the indication, of developing medicine for adults as well as for children. It means that the development of cancer drugs for children is now compulsory, rather than simply an “exemption” by default due to the fact that most pediatric cancers reside under the orphan disease status. In fact, the number of oncology clinical trials have been increased from 5,000 in 2,000 to 23,000 in 2018, a nearly 4x fold increase.

With the implementation of RACE Act, the number of pediatric oncology studies is not expected to decrease—rather, an increase of pediatric oncology clinical studies is anticipated in order to allow cancer drugs into the market. The RACE Act will undoubtedly provide challenges to pharmaceutical companies when developing cancer drugs for children, as the disease course and presentation of pediatric cancers are different from adult cancers.

Due to the physical, mental, and psychological development differences between children and adults, clinical trials to assess treatment benefits and safety for pediatric trials could be prolonged. As the development of cancer drugs will get increasingly diverse and intensive, this may create opportunities for pharmaceutical companies to examine and explore new treatments for cancer and for clinical research companies like PRA to help develop pediatric oncology research trials for these patients.

The use of digital technology has helped improved efficiencies for clinical trials e.g., patient enrollment, decentralized trials, wearable tech, etc. Can you speak to the benefits of this to you as a researcher and to the patient with respect to oncology clinical trials?

Digital technology has transformed the clinical trial development process, especially with the increase use of wearable and mobile technologies along with cloud technology.

From a researcher’s perspective, online platforms could enable the collection of frequent, specific, and multi-dimensional data throughout the length of trials in a timely manner. The technology has the potential to assist and to provide innovative trial designs and endpoints in trials, improve the patient experience, and assist patient recruitment and retention via relevant online tools.

By personalizing patient access using password-controlled mobile platforms (e.g., mobile/cell phone), the patient could report any adverse event correctly and in real time, thus avoiding or minimizing missing/incorrect safety information. Moreover, reminders could be sent to the patient in order to avoid missing study visits. The online platform could also provide up-to-date information regarding the patient’s target disease and study particulars.

All of these benefits will improve data quality and enhance patient retention for a study.

Learn more about PRA’s Mobile Health Platform

What are you most excited about in terms of what the future holds for treatments for these cancers?

The current standard treatment of certain cancers could be history in five years. The momentum of investigating new treatment for unmet medical needs never fades. The trend of oncology trials works towards precision medicine on specific molecular targets of selected patient populations. Furthermore, an increasing exploration of biomarkers leads to the investigation of new cancer drugs and mechanisms of action, which could improve both safety profile and treatment benefit of the new medicine.

With all of these new methods, together with the exploration of gene editing, cancer treatment will ultimately become a personalized therapy. That is what I am most excited about!

PRA supports oncology and hematology clinical projects globally—in every phase and virtually every indication, including supportive care. Our in-house oncology and hematology experts make the complex, simple. PRA's global project management and clinical operations team members have an average of 10+ years of study experience each.

Learn more about our expertise in oncology.

Read more

You may also be interested in: