Promising results for a new Colorectal Cancer Treatment

A new tablet treatment called divarasib has shown it is very effective in treating a challenging type of Colorectal Cancer associated with the KRAS G12C mutation. Research, published in Nature Medicine, has shown remarkable results in 62% of people with KRAS G12C mutated Colorectal Cancer achieving a positive response to treatment when given divarasib in combination with another treatment called cetuximab. These results are incredibly impressive.

Although the KRAS G12C mutation only occurs in approximately 4% of patients with Colorectal Cancer, it is routinely tested for, so researchers’ ability to identify the right patients to offer such trial treatment to is straightforward. The median progression-free survival for patients in the study was just over eight months and the treatment was well tolerated with manageable side effects. While this is not a head-to-head trial, the response rates are better than what the researchers have seen with other treatments that work on the KRAS G12C mutation pathway.

The researchers are very hopeful that this combination of divarasib with cetuximab will translate into better outcomes for Colorectal Cancer patients. Early drug development trials require a very experienced team with specialized skills and the team have to be extraordinary at ensuring the best for the patients and trial compliance. KRAS is a key protein that controls how cells divide and survive and when the KRAS-G12C protein mutates it makes cells, including cancer cells, more likely to divide uncontrollably leading to the development of tumors.

Colorectal Cancer starts in your colon, the long tube that helps carry digested food to your rectum and out of your body. It develops from certain polyps or growths in the inner lining of your colon. Healthcare providers have screening tests that detect polyps before they can become cancerous tumors. Colorectal Cancer that is not detected or treated may spread to other areas of your body.

Thanks to screening tests, early treatment, and new kinds of treatment, fewer people are dying from it.

Your colon wall is made of layers of mucous membrane, tissue, and muscle. Colorectal Cancer starts in your mucosa, the innermost lining of your colon. It consists of cells that make and release mucus and other fluids. If these cells mutate or change, they may create a colon polyp. It usually takes about 10 years for cancer to form in a colon polyp. Left undetected or untreated, the Colorectal Cancer works its way through a layer of tissue, muscle, and the outer layer of your colon.

Then it may also spread to other parts of your body via your lymph nodes or your blood vessels. It is the third most common cancer diagnosed in people in the United States. According to the Centers for Disease Control and Prevention, men are slightly more likely to develop colon cancer than women. Colorectal Cancer affects more people who are Black than people who are members of other ethnic groups or races.

Colorectal Cancer typically affects people age 50 and older. Over the past 15 years, however, the number of people age 20 to 49 with Colorectal Cancer has increased by about 1.5% each year. Medical researchers are not sure why this is happening. You can have it without having symptoms. If you do have symptoms, you may not be sure if changes in your body are signs of it.

It happens when cells grow and divide uncontrollably.

All cells in your body are constantly growing, dividing, and dying. That is how your body remains healthy and working as it should. In this case, cells lining your colon and rectum keep growing and dividing even when they are supposed to die. These cells may come from polyps in your colon. In October 2023, one hurdle that is often overlooked is needle phobia, which can leave many kids downright terrified of getting a shot that can provide them with protection over the course of a season, or even a lifetime.

With the school year well underway, holiday travel just around the corner, and the spread of respiratory pathogens already in full swing, pediatricians are trying to shield as many kids as possible from the possibility of severe outcomes from preventable illnesses. Indeed, estimates have indicated that as many as two in three children have needle phobia. Needle phobia can be learned from a past experience of pain, but there is also a biological component that makes some people react very strongly to the idea of procedures involving a needle.

Needle phobia can make procedures feel more painful, lead to severe panic, and in some cases to a physical response that causes fainting. Furthermore, needle phobia may lead to the avoidance of vaccines altogether, with the Centers for Disease Control and Prevention (CDC) reporting that as many as one in 10 people might delay the covid vaccine due to needle phobia. In the case of young patients, needle phobia may stress both the child and parent.

It is an art and a science to practice pediatrics.

A pediatrician’s office is an ideal spot for kids to receive vaccines because this type of setting is uniquely positioned for giving the greatest comfort, and providers in this setting are uniquely trained to interact with and care for infants and toddlers. It is essential to start with parents when it comes to addressing needle phobia in kids. A lot of it is communication with the parents, especially for the new parents.

Explaining everything in detail goes a long way, and this is especially true in regards to the benefits of vaccination. As for the need for needles, the big picture is that they are simply the modality for getting the best protection for life. However, there are techniques to help soothe anxious children. Healthcare providers can use techniques aimed at distracting the child while they receive a shot, or they can give a vaccine while the child sits in their parent’s lap, it is important to have the parent present.

Indeed, a systematic review published in Pediatrics indicated that non-digital distraction strategies, such as singing or blowing bubbles, were as effective as digital distraction strategies, such as virtual reality, or listening to a book or music. In addition, it is important for parental involvement in helping to achieve a positive, calm, and even pain-free poke. Some parents do not speak up because they feel intimidated, or the doctor or nurse does not ask.

They may worry that they will upset someone.

It is okay to speak up when you know what works for your child. Your pediatrician needs and wants your input. Often, the potential needle phobia among young patients is simply accepted as part of the process. However, this issue can negatively affect the receipt of important vaccines and other healthcare services, such as routine blood draws. There are ongoing efforts to help address needle phobia in young patients.

For example, the Comfort, Ask, Relax, Distract (CARD) framework developed in Canada. Benefits of CARD include reducing stress-related reactions, including fear, pain, dizziness, and fainting during vaccination. It is also said to improve the vaccination experience not only for the person receiving a vaccine, but also the educators, parents, and healthcare providers who support them.

Recent research related to CARD included the evaluation of a web-based game that uses the framework to teach kids how to cope with needles. School-age children and their parents liked the CARD game and learned coping strategies they would use during future needles. Overall, when it comes to vaccination in young patients, actually planning it out is much more effective.

Children may be able to make decisions on matters like whether they want to be on their parent’s lap while receiving the vaccine, as well as what tools they would like to have present for distraction, such as the ability to watch a YouTube video or play their favorite game.

These preferences can be communicated with healthcare staff to partner on the process. There is more of a movement now to actually recognize that we can make this process better and less fearful. In October 2020, a group known as the Data and Safety Monitoring Board (DSMB) held powerful sway over which covid vaccines would end up on the market. Members of a DSMB were the only ones who got to look under the hood while a trial was ongoing.

DSMB members knew who had gotten a covid vaccine, and who had gotten a placebo. The very doctors running the trials, the pharmaceutical companies that developed the vaccines, and even the United States Food and Drug Administration (FDA) did not know. Armed with that secret, only the DSMB could monitor how safe and effective a vaccine was shaping up to be.

One word from the DSMB, and a trial could be stopped. That was what happened to the AstraZeneca trial in early September 2020 after a study participant developed neurological symptoms. Shortly after, it came to light that the same trial had been paused briefly in July 2020 for similar reasons. While the vaccine trial resumed in the United Kingdom, it was paused in the United States.

In early 2020, the National Institutes of Health (NIH) appointed a common DSMB to monitor covid vaccine clinical trials that were being funded by the federal government under Operation Warp Speed.

This DSMB had 10 to 15 members with specialties including vaccine development, statistics, and ethics. It was not a glamorous or public-facing job. DSMB members were paid only a modest honorarium by the NIH at just $200 per meeting, there were no press conferences, no TV interviews, no fame, and no glory. That was because DSMB members’ names were not typically revealed while trials were in progress to shield them from external pressures.

Various types of people might try to influence DSMB members, it did not have to be nefarious. Parents of a very ill child might be anxious about how the trial of a drug that could help their child is going, and they might contact the folks at the DSMB. Keeping DSMB members’ names private was a way to preserve independence of the group. There was a lot at stake.

DSMB members scrutinized the data carefully. One word from them, and a vaccine’s chances of coming to market could be squashed. Millions of dollars spent on research and development could all be for naught. In order to reach population immunity through a vaccine, a large proportion of the United States public needed to get vaccinated. But confidence in a potential vaccine was low.

The job of the DSMB was to monitor the data that came out of clinical trials.

In clinical trials, there could be thousands, or tens of thousands, of study participants. Some were randomly assigned to receive an intervention and some received a placebo. The studies were double-blinded. The participants did not know which they were getting, and neither did the doctors running the trials. If a study volunteer had a side effect or an adverse event, the DSMB could look and see if they received the vaccine or the placebo.

If it was a placebo, then it was one of these random things. If it was the vaccine, it could still have been a random thing. But if these events were concerning enough, the DSMB could recommend that the trial be stopped for safety reasons. The stakes were especially high in covid vaccine trials, which might ultimately be administered to millions of healthy people, unlike drug trials intended for those who were already sick and might have few options.

Even an adverse event that happened as infrequently as one in 10,000 people or one in 20,000 people would be a lot of people who would have a serious adverse event. At pre-determined intervals, the DSMB also checked on efficacy. If people receiving the vaccine got sick roughly as often as those who got the placebo, that was not a good sign. The board could recommend that the trial be stopped due to futility.

The board might also look at the quality of the data.

If there was missing data, participants who dropped out, or if the trial was being conducted poorly, it was the DSMB that could weigh in. Most of the time, a data monitoring committee would say everything looked fine, but sometimes a hard decision was going to have to be made, and that was the value of these committees. Conversely, if it looked like the vaccine was working exceptionally well, the DSMB might recommend that the study sponsor submit an application to the FDA before the official end of the trial, in order to get it more quickly to market.

The people who served on these committees were thoroughly vetted for conflicts of interest. Members were screened to make sure they did not have a financial interest in the pharmaceutical company that was sponsoring the vaccine trial. DSMB members or their family members should have no professional, proprietary, or financial relationship with the sponsoring companies.

Selected DSMB members and their family members were not allowed to work for other companies developing covid vaccines. It was unprecedented to have a DSMB with that much authority. Typically, each clinical trial had its own DSMB. Such was the case with Pfizer, whose trial was neither under the common DSMB nor funded by the government. Pfizer’s DSMB comprised a chairperson and 4 additional members that met on a weekly basis, that small for a trial that aimed to enroll up to 44,000 participants.

In large trials, you got to have a bioethicist, virologist, an immunologist, epidemiologist, all the critical areas covered.

It was a big honor to be named to a DSMB, there was plenty of motivation to serve on these boards. President Donald Trump claimed the White House could overrule the FDA’s attempt to toughen its covid vaccine guidelines. It never occurred to anybody that anyone outside the FDA would try and interfere with that. In September 2020, since March 2020, we had been forced to rethink our handling of personal space.

Dictating our distance from other humans was a rule of thumb that defined close contact. If you were within 6 feet of someone for more than 15 minutes, it was potentially dangerous. This was the rule that federal and state health departments used to determine whom needed to be contacted after someone tested positive for covid, and it was a rule that many Americans were using to determine their risk when going shopping or seeing friends.

Restaurant servers adhered to it by not lingering at tables. News anchors adhered to it on TV, their seats carefully spaced out. But as we moved indoors in increasing numbers, the underlying assumptions that made 6 feet and 15 minutes a rule to live by were no longer correct. To reflect the risk that came with gathering indoors, and our evolving understanding of how covid could be spread, we needed to rethink the formula for close contact.

We had been aware for a while that the main way you became infected with covid was through inhalation of virus-containing particles, this was why we had physical distancing. Those particles came from the airway of an infected person who coughed, sneezed, sang, yelled, or even just spoke and breathed.