The Case of Samantha
Samantha was a 54 year-old woman living in British Columbia, Canada, with previously treated high-grade serous ovarian cancer that had returned.
When she came to us, Samantha had completed all of the standard chemotherapy regimes and was quickly running out of options for further treatment. Additionally, the years of fighting her disease had left her financially destitute.
Samantha wasn’t ready to just accept this and so she reached out to us.
How we helped Samantha using our 5-step system
1. Interim support/Initial personalized research
When Samantha first came to us, tumor DNA sequencing was not yet available at a reasonable cost, so we had Samantha ask her BCCA oncologist to get a previous biopsy sample tested for a breast cancer receptor known as HER2 as this alteration is found in certain cases and can suggest a sensitivity to HER2 targeted drugs.
Secondly, we used public and private patient databases to identify the top 10% of genetic alterations and molecular features that drive high grade serous cancers, and designed a diet and supplement plan to inhibit them as much as possible.
This change in diet alone resulted in a drop of her CA125-3 tumor markers from 110 to 81.2!
2. Introduced advanced diagnostics
After some time, Samantha informed us that while she had been able to convince her BCCA oncologist to get HER2 testing performed, the oncologist had told her that they would only share the results of the test with her if she promised not to discuss it any more as they would be unable to use the results of this test for drugs that were not approved for her type of cancer.
Since the test was strongly positive for HER2, and there were, in fact, some very beneficial treatment options available to her, we had Samantha contact a new oncologist that would consider prescribing anti-HER2 medications off label for her.
3. Personalized Research
We then researched currently available HER2 drugs and found that a new combination of two anti-HER-2 drugs called Herceptin and Pertuzumab was getting significant results compared with the standard protocol of Herceptin alone. Based on these data, and the fact that Samantha’s cancer had not yet metastasized outside of her lymphatic system, we suggested that she started on this combination.
An additional benefit for Samantha of this treatment protocol, which is a very common benefit to targeted cancer therapy in general, is that the drug combination we recommended was made from humanized antibodies that only targeted the cancer cells and therefore she experienced minimal side effects during and after treatment.
4. Interim Treatment Support
Although her finances were very limited, Samantha was able scrape enough money together to pay out of pocket for a few months of this dual treatment, which amounted to approximately $12,000 per month.
We also suggested that she utilize a social media “fund me” patient support website to help pay for the cost of these two drugs, and we promoted her ‘fund me’ page via our social media pages.
While initially the drugs resulted in a significant drop in Samantha’s CA125 levels, her levels started to creep back up and a BCCA funded CT scan indicated that the combination of drugs may not be working.
To be sure, we contacted a local PET-CT clinic that was able to offer a free scan to Samantha. This was crucial to her treatment outcome as the results of this scan showed that although some of her tumors had not responded, others were responding well to the treatment. Without the scan Samantha would have been deemed to be unresponsive and she would have believed her treatment wasn’t working, when in reality it was.
Additionally, while some of the tumors had not shrunk in size they showed lowered PET serum uptake values (SUVs), which indicated that her less aggressive tumors that 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 the chance of having this drug combination funded by BCCA was not an option, so Samantha had to stop taking them after 3 months.
5. Clinical Trial support
Given the lack of genetic tumor DNA sequencing information for Samantha and her limited finances, we then performed computer and statistical modelling to identify potential treatments, and recommended that Samantha participate in a local BCCA trial using a drug known as a PARP inhibitor.
Samantha asked her new BCCA ovarian cancer specialist to apply for the trial but unfortunately, she was denied. We were not prepared to accept this and immediately contacted the drug makers directly and were able to convince them to allow Samantha to participate in the trial.
After an initial response and 6 months on the trial, Samantha was removed due to a CT scan showing a possible increase/lack of shrinkage in her lymph node tumors.
Following this, Samantha’s BCCA specialist oncologist had Samantha participate in a newer untested immune-based therapy called Monalizumab, which was being offered exclusively in Canada.
Since we did not have any data for this new drug, and since it was a Phase 1 dose determining trial that was not offered outside of Canada, we could not confirm that it would benefit Samantha however, she decided to give it a try.
Once again, Samantha initially responded to this drug with a rapid decrease in CA125-3 (dropping from 2100 to 1300), but after 3 months, Samantha was removed based on the results of a CT scan showing minimal size increases in a few lymph nodes and changes in the shapes of others.
As before, Samantha really needed a PET-CT to identify if this drug is working for her or not, but she cannot afford one and the trial does not use them.
We asked her to reach out to her new oncologist and to share the information we provided to her regarding the problems with using the RECIST criteria and the results of a CT scan in determining if an immune therapy is working or not.
While her oncologist initially denied her request based on the mistaken assumption that the trial was using the immune based criteria, her request was recently honored and she is currently scheduled for a PET-CT via BCCA.
A note on the importance of accurate assessment of treatment success.
While we have reviewed her latest CT scan, it is not clear how her disease has progressed as the results are based on the traditional RECIST response criteria and 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 tumor (live or dead).
In short, the RECIST looks at the size of a tumor and does not consider other aspects such as delayed responses or pseudo progression (the enlargement of tumors due to an immune response and infiltration of immune cells into the tumor).
The Immune Response criteria that should be used to assess the efficacy of these treatments are the new response criteria designed specifically for use with these new immune therapies. Rather than simply just considering if a tumor 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 tumor burden.
(c) Response after an increase in total tumor burden (meaning, tumors may increase initially due to the bodies natural immune response and then respond by shrinking).
(d) Response in the presence of new lesions, meaning new lesions appear due to the presence of tumors that were initially too small to be seen with a scan but which have become larger and visible due to immune infiltration.
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 favorable increases in life-expectancy. In other words, there are many cases when an initial lack of tumor shrinkage, the growth of a tumor or the identification of new tumors, 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 that 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 that respond after the trial is finished often go unnoticed as they are not part of the reported outcomes.
At CTOAM we use a combination of PET-CT’s 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.
So Far So Good for Samantha!
We do hope that Samantha is a late responder and we are hopeful that her upcoming PET-CT will confirm this.
We have also suggested that she ask her oncologist to prescribe either Lapatinib, which is a newer smaller-molecule HER2 inhibitor that unlike the large and bulky antibody based drugs (Herceptin and Pertuzumab), may have an easier time reaching tumors that are deep within the lymphatic system, or pembrolizumab, a PD-1R inhibitor (immune based).
Unfortunately, despite the scientific data supporting this approach to treatment, Samantha was told by her oncologist that she would need to access these treatment options privately and pay out of her own pocket.
While at first glance, it may appear that Samantha has been through a relentless pursuit of ineffective therapies, the reality is something else.
Since advanced cancers are genetically diverse, there is no one therapy that is likely to affect all of the tumors at the same time, and Samantha will naturally have to engage in a variety of targeted therapies in an attempt to turn her deadly form of cancer into a chronic but manageable disease. This is exactly what she has been able to do so far.
It is very significant that Samantha’s form of cancer, which is usually very deadly, has not metastasized beyond her lymphatic system since she first called us, and over 11 years after her initial diagnosis and treatment!
As you can see, even if you are not able to explore detailed genetic testing, CTOAM’s records reviews and personalized research and advocacy services can result in significant benefits to the outcome of your treatment.
Given that we now know that cancer is unique to every person, having access to a team of knowledgeable scientists, doctors and advocates that are working for you rather than trying to make you fit some pre-established protocol makes a huge difference in the outcome of your disease!
If you or a loved one is fighting cancer, contact us for a brief review of your medical records to make sure that you are doing all that you can do to beat Cancer. Call us anytime at (778) 999-5463 or email email@example.com.