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Samantha is a 54-year-old woman living in British Columbia, Canada. She’d previously been treated for high-grade serous ovarian cancer, which had returned.
When she contacted CTOAM, Samantha had completed all of the standard chemotherapy regimes. She was quickly running out of options for further treatment. Plus, the years of fighting her disease had also left her financially destitute.
Samantha wasn’t ready to accept this, so she reached out to CTOAM.
1. Interim Support and Personalized Research
When Samantha first came to us, tumour DNA sequencing was not yet available at a reasonable cost. So we suggested that Samantha ask her oncologist at BCCA (British Columbia Cancer Agency) to get a previous biopsy sample tested for a breast cancer receptor known as HER2. This alteration is found in certain cases and can suggest a sensitivity to HER2 targeted drugs.
Then our Cancer Care Research and Advocacy Specialists used public and private patient databases to identify the top 10% of genetic alterations and molecular features that drive high grade serous cancers. From this data, we designed a diet and supplement plan to inhibit them as much as possible.
This change in diet alone resulted in a drop of Samantha’s CA125-3 tumour markers from 110 to 81.2! Never underestimate the power of nutraceuticals.
After some time, Samantha shared some further information with us. Although she’d managed to convince her BCCA oncologist to get the HER2 testing performed for her, there had been a catch: the oncologist had said that they’d only share the results of the test with her if Samantha promised not to discuss it any more. This is because the BCCA oncologist would be unable to use the results of this test for drugs that were not approved for her type of cancer.
The test result was strongly positive for HER2, which meant that there were some very beneficial treatment options available to her. So CTOAM had Samantha contact a new oncologist who would be more open to prescribing anti-HER2 medications off label for her.
Our specialists then researched currently available HER2 drugs. We found that a new combination of two anti-HER2 drugs (called Herceptin and Pertuzumab) was getting significant results compared with the standard protocol of Herceptin alone. Based on this data, and the fact that Samantha’s cancer had not yet metastasized outside of her lymphatic system, we suggested that she start on this combination.
Although her finances were very limited, Samantha was able to scrape enough money together to pay out of pocket for a few months of this dual treatment. The treatment amounted to approximately $12,000 CAD per month.
While initially the drugs resulted in a significant drop in Samantha’s CA125 levels, her levels started to creep back up. A CT scan (funded by BCCA) indicated that the combination of drugs may not be working.
This data was crucial to her treatment outcome: without it, Samantha would’ve been deemed to be unresponsive to the current treatment. She and her treatment team would’ve thought that the treatment wasn’t working when, in reality, it was working.
Additionally, while some of the tumours hadn’t shrunk in size, they still showed lowered PET serum uptake values (SUVs). This indicated that her less aggressive tumours were possibly in decline and less likely to metastasize.
This is an important consideration, as these two drugs function in part by creating an immune response that can have a long term beneficial effect in reducing disease burden.
Unfortunately, it wasn’t possible for BCCA to fund this particular drug combination. So Samantha had to stop taking them after three months.
Given the lack of genetic tumour DNA sequencing information for Samantha and her limited finances, we performed computer and statistical modelling to identify other potential treatments.
a) Finding the right trial: Our specialists recommended that Samantha participate in a local BCCA trial using a drug known as a PARP inhibitor.
b) Applying for the trial: Samantha asked her new BCCA ovarian Cancer Care Research and Advocacy Specialist to apply for the trial. Unfortunately, she was denied. CTOAM immediately contacted the drug company directly. Our Cancer Care Research and Advocacy Specialists were able to convince the company to allow Samantha to participate in the trial.
c) Participating in the trial: After an initial response and six months on the trial, Samantha was removed from the trial. This was due to a CT scan showing a possible increase and lack of shrinkage in her lymph node tumours.
d) Finding a different trial: Following this, Samantha’s BCCA specialist oncologist had Samantha participate in a newer, untested immune-based therapy called Monalizumab. This trial was being offered exclusively in Canada.
e) Pros and cons of new trials: Because CTOAM didn’t have any data for this new drug – and since it was a Phase 1 dose determining trial only offered within Canada – our experts could not confirm whether it would benefit Samantha. However, she decided to give it a try.
f) Results of trial participation: Once again, Samantha initially responded to this drug with a rapid decrease in CA125-3 (dropping from 2100 to 1300). But after three months, Samantha was removed again based on the results of a CT scan showing minimal size increases in a few lymph nodes and changes in the shapes of others.
g) Insufficient treatment monitoring: Like before, Samantha really needed a PET/CT to identify if this drug was working for her or not. Unfortunately, she could not afford one and the trial does not use them.
Our care team encouraged Samantha to share the results of the clinical trial with her new oncologist. We felt her oncologist might be more inclined to order her a PET/CT scan if she knew about the information that CTOAM had gathered from the clinical trial (regarding the problems with using the RECIST criteria and using the results of a CT scan to determine if an immune therapy is working or not).
At first, Samantha’s oncologist denied her request based on the mistaken assumption that the trial was using the immune-based criteria. However, her request was recently honoured and she is currently scheduled for a PET/CT funded by BCCA.
Accurate treatment monitoring is fundamental to treatment success.
While CTOAM has reviewed Samantha’s most recent CT scan, her disease progress remains unclear. This is because the CT scan results are based on the traditional RECIST response criteria – not the immune-based criteria that these new immune therapies need to be assessed by for accuracy. RECIST is not an accurate assessment approach for immune-based therapies because it does not consider the actual status of the tumour (live or dead).
Rather than just considering if a tumour has increased in size or not, there are four distinct response patterns that are considered in order to determine whether a patient is responding well to the immune-based treatment. For example, cases of the following responses have been observed in up to 30% of patients on immune targeted drugs:
a) Shrinkage in baseline lesions without new lesions.
b) Durable stable disease in some patients followed by a slow, steady decline in total tumour burden.
c) Response after an increase in total tumour burden (meaning, tumours may increase initially due to the body’s natural immune response, and then respond by shrinking).
d) Shrinkage in baseline lesions without new lesions.
Response Patterns for Immune-Based Therapies
It is important to be aware that the above response patterns can occur in patients who receive immune-based therapies and that these patterns can be associated with favourable increases in life expectancy. In other words, there are many cases when an initial lack of tumour shrinkage, the growth of a tumour, or the identification of new tumours can be explained by an active immune response, and in those cases, should be seen as a positive sign.
In fact, we have seen cases of delayed responses of more than a year occurring in patients who had been prematurely removed from immune based clinical trials due to the results of a CT scan and based on RECIST criteria. Since many trials only monitor patients during the course of the trial, patients who respond after the trial is finished often go unnoticed as they are not part of the reported outcomes.
Better Treatment Monitoring: PET/CT and Liquid Biopsy
At CTOAM we use a combination of PET/CTs and liquid biopsies to determine if a patient has indeed responded or not. These diagnostic tools give us a clear picture of how well a treatment is working so we can, with confidence, continue with the current protocol or make rapid adjustments as necessary, to create the greatest chance for a successful outcome.
6. Patient Outcome
We are hopeful that Samantha is a late responder and that her upcoming PET/CT scan will confirm this.
CTOAM has also recommended that Samantha ask her oncologist to prescribe either Lapatinib or pembrolizumab (an immune-based PD-1R inhibitor). Lapatinib is a newer, smaller-molecule HER2 inhibitor. Unlike the large and bulky antibody-based drugs (Herceptin and Pertuzumab), it may have an easier time reaching tumours that are deep within the lymphatic system.
Ovarian Cancer Treatment Success
From Deadly Diagnosis to Manageable Condition
Samantha has managed to turn her deadly form of cancer into a chronic but manageable disease. This is a significant success for Samantha’s form of ovarian cancer, which is usually very deadly.
In fact, her cancer has not metastasized beyond her lymphatic system since she first called CTOAM – and over eleven years after her initial diagnosis and treatment!
So while, at first glance, it may appear that Samantha has tried many ineffective therapies, the reality is something much more positive.
The fact that this is possible should bring hope to ovarian cancer patients, and their loved ones, around the world.
As you can see, CTOAM’s advanced diagnostics, records review, and consultations can result in significant benefits to a patient’s outcome. Having access to a team of precision oncology specialists, doctors, and patient advocates can make all the difference in the outcome of your disease.
If you or a loved one has cancer, contact us today so we can do a brief review of your medical records. CTOAM’s cancer research and patient advocacy experts will ensure that you have access to the most advanced tests and treatments available for your unique form of cancer – as close to home as possible.
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