Updates and Commentary on the Latest in Cancer
By Dr. Ajaz Bulbul
Immunotherapy and oral targeted treatment in aggressive prostate cancer
There is now new evidence that immunotherapy may have some valuable benefits in patients with aggressive prostate cancer, which was formerly thought to be completely resistant to this form of therapy. A recent study in a cancer journal Oncotarget showed that advanced prostate cancers with the AR-V7 biomarker (which can be tested for by a blood test) may be a marker for aggressive disease and, may have a larger amount of DNA gene abnormalities and increased complexity which would thus make it sensitive to immunotherapy as we know that tumor’s with high number of abnormalities and mutations respond better to immunotherapy.
The study included 15 patients with AR-V7 positivity and treated with the checkpoint inhibitors called ipilimumab and nivolumab, and even though there was more toxicity (possibly from ipilimumab), the population of patients chosen had advanced prostate cancer with a poor prognosis. The patients with AR-V7 biomarker positive blood test had the best response to this type of combination immunotherapy.
A new class of drugs called PARP inhibitor, such as olaparib which is commercially available for treating breast and ovarian cancer which may provide synergistic effects when combined in some patients with immunotherapy. As observed in a earlier phase II study of olaparib and durvalumab with enrollment of 17 patients with advanced prostate cancer.
Thus, there may be an additional tool for use in patients with BRCA2 mutations such as breast, ovarian, or pancreatic cancers. I this study 12 of the 17 men had reductions in PSA levels, with eight having PSA declines of more than 50%.The study discovered that 7% of men may show susceptibility to this treatment. In the near future tumor studies and genetic marker tests will be routinely used to identify the subset of men with a particular genetic change, who can be considered for immunotherapy.
Metastatic breast cancer treatment with targeted drugs
A significant change is happening in treatment of wide spread metastatic breast cancer that have positive hormone receptor status the commonly known ER positive breast cancer. Previously hormone blocking pills like tamoxifen or anastrozole, letrozole etc alone have been used to control the disease.
Now among other important studies another large phase III study called the MONALEESA-3 trial evaluated a targeted oral non chemo drug called ribociclib plus fulvestrant (hormone blocking injection) in patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer who had never received treatment or had received up to one line of prior endocrine therapy.
Over 484 postmenopausal women were randomly assigned to the new drug ribociclib plus fulvestrant, and 242 were assigned to endocrine therapy alone. Patients on the combination of the targeted drug (CDK inhibitor) and endocrine therapy did not have any progression of disease (Median progression-free survival) of nearly 20 months versus 12.8 months respectively with endocrine therapy which was a significant 41% improvement. Overall response rate was 41% for the combination treatment compared to 28% for single endocrine drug.
There were some more side effects of the combination treatment with drop in white cell count reported in 46% in the combination arm compared to 0% in single agent endocrine therapy as expected. However, despite this dose adjustments and interruptions were able to overcome this effect in most expect 5% who could not continue the treatment due to severe side effects. Monaleesa 3
Breast cancer treatment may worsen weight gain and increase risk of diabetes
More than 90% of patients with estrogen-receptor (ER) positive early stage breast cancers are alive 20 years after their breast cancer diagnosis. It is important to recognize the long-term effects of adjuvant hormonal blocking therapy therapy, especially now that extended therapy for almost 10 years is recommended in certain high-risk breast cancer subgroups.
A study published in the Journal of Clinical Oncology earlier this year that hormonal therapy in breast cancer is a significant risk factor for diabetes. This finding is similar to that previously reports published in the journal Cancer and British Journal of Cancer. The study found aromatase inhibitors like anastrozole and letrozole to be associated with a higher risk of diabetes in comparison with tamoxifen. The risk was 4 times higher with aromatase inhibitors and 2 x higher with tamoxifen. There are established studies connecting obesity and increased weight with higher risk of recurrence in breast cancer as week.
We need to understand that the strong recommendation for adjuvant hormonal blocking therapy in ER-positive breast cancers for 5 to 10 years remains as strong as before we just need to understand that weight management and active lifestyle to avoid obesity should be the goal. The benefit of endocrine therapy clearly the benefits outweigh the risks.
We need to emphasize the importance of a healthy lifestyle in breast cancer survivors since for them it’s even more important to stay fit and avoid being overweight. Moderate-intensity physical activity of at least 150 minutes per week has been shown to improve breast cancer outcome and extremely important in decreasing the risk of recurrence in our breast cancer survivors decrease the risk of diabetes and thereby helping prevent recurrences.
Q: I have metastatic stage IV esophageal cancer and am receiving chemotherapy. How long will I be on treatment?
A: I am sorry to hear about your cancer. Stage IV disease is usually incurable. Esophageal cancer has two variants (squamous cell, adenocarcinoma). GERD, reflux can increase the risk of adenocarcinomas that are increasing in incidence. Squamous esophageal cancers are usually caused by alcohol and smoking. Metastatic disease in both cases is treated with chemotherapy.
On progression if your tumor expresses a marker called PD1 you may be eligible for immunotherapy which may be better tolerated however response rates are still low and cures are rare. Therefore, you may continue treatment as long as you are responding or the disease progresses or you have side effects that limit the use to treatments.
Q: I have metastatic colon cancer. I’m on treatment for the past 2 years. How long should i expect to continue treatment. What is my expected life span?
A: I am glad you are doing well. I’m sorry about the diagnosis. Although colon cancer even if metastatic to liver in some settings may still be curable in up to a quarter of patients with stage IV disease. These patients need to have limited liver disease and an excellent response to chemo to qualify for curative surgery of liver and colon lesions.
In your case it seems since you’ve been on chemo alone for two years this may not a surgical case. The median survival of colon cancer now may reach over 34-38 months with chemotherapy alone. In colon tumors that are MSI deficient (a test that may be done on the tumor itself) you may qualify for targeted immunotherapy that have been shown to have long term excellent responses with limited side effects. You may want to talk to your oncologist about that testing.