Difficult-to-treat Cancers Pt 3: Recent Advances in the Treatment of Cancer

By: Harvey Berger, MD

Cancer treatment has advanced significantly over the past few decades, due in large part to research performed by pharmaceutical companies.

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By: Over the past twenty years, a number of pharmaceutical and biotechnology companies have invested in cancer research and brought new drug therapies to the market. Between its founding in 1991 and its sale to Takeda Pharmaceuticals (and incorporation into Takeda Oncology), ARIAD Pharmaceuticals brought a number of innovative medicines through clinical research. These drugs have improved the prognosis for patients diagnosed with difficult-to-treat cancers, including non-small cell lung cancer (NSCLC) and multiple forms of leukemia.

Recent Advances in the Treatment of Cancer

Below I discuss a number of advances in treatments for difficult-to-treat cancers. This is not an exhaustive list of all treatment options for these cancer types and patients should discuss all treatment options with their doctor before deciding on the best path for them.

ALK-positive non-small cell lung cancer

According to the American Lung Association, the five-year survival rate for lung cancer patients is 18.6%. The American Cancer Society claims that patients with NSCLC have a 23% 5-year survival rate.

One of the top reasons these numbers are so low, particularly in ALK+ cases, is because tumors can develop a resistance to the medications used to treat them. ALK+ (anaplastic lymphoma kinase positive) NSCLC causes a mutation of the ALK protein, which is involved in cell reproduction.

According to the 2017 ALTA report, the study involved two groups and showed positive results. Group A received 90 mg of Brigatinib daily and Group B received 180 mg of Brigatinib daily, after a 7-day lead in of 90 mg per day.

The one-year overall survival rate was 70% for Group A and 80% for Group B. Following this study, the FDA approved Brigatinib under their Accelerated Approval regulations and allowed it to be brought to market. Results from a Phase III trial comparing Brigatinib to Crizotinib in patients with ALK+ NSCLC were released in 2018 and showed that treatment with Brigatinib resulted in longer progression-free survival for patients.

Another medication that was recently approved to treat ALK+ NSCLC is Lorlatinib, produced by Pfizer. Similar to Brigatinib, Lorlatinib is capable of overcoming resistances that occur in ALK+ NSCLC tumors and was granted accelerated approval in November 2018 following a phase 2 trial in patients with ALK+ or ROS1+ advanced NSCLC.

The results led to the conclusion that lorlatinib showed positive activity in patients with ALK+ NSCLC, whether they were treatment naive or had been treated with up to three ALK TKIs, and led to its approval by the FDA.

Late Stage NSCLC

According to the American Cancer Society, the five-year survival rate for patients diagnosed with Stage IIIB NSCLC is 26%, Stage IVA is 10% and Stage IVB is less than 1%. There aren’t many treatment options for patients diagnosed with late-stage NSCLC, but research in this area has grown in the past few years.

Patients either received osimertinib or a standard EGFR-TKI and the median PFS was significantly longer in the osimertinib group at 18.9 months, compared to 10.2 months in the other group.

TAK-788 is another TKI that is currently undergoing a Phase I/II study, sponsored by Millennium Pharmaceuticals and Takeda Oncology, to determine its efficacy against advanced NSCLC tumors. It is currently being tested on tumors that contain an EGFR or human epidermal growth factor 2 (HER2) mutation.

Philadelphia chromosome-positive leukemia

Philadelphia chromosome-positive (Ph+) accounts for approximately 25% of acute lymphoblastic leukemia (ALL) cases in adults and 3% of cases in children, according to the Leukemia & Lymphoma society.

The Philadelphia chromosome contains an abnormal gene, called BCR-ABL, which helps leukemia cells grow. This disease is treated with TKIs, which block the abnormal protein and stop the cells from growing. The introduction of TKIs in the early 2000s began improving the survival rate for patients with Ph+ leukemias.

Nilotinib, created by Novartis Pharmaceuticals, is a second-generation TKI that was developed to treat Ph+ Leukemias, a disease which has an overall survival rate of less than 20% when treated with only chemotherapy.

Sarcoma Treatment

The discovery that Ridaforolimus is capable of both combating cancer as well as treating CAD shows that it’s important for drug sponsors to follow the data and use medications to fight any disease they prove effective against, regardless if it was for their original intended use.

Immunotherapies

Immunotherapy has become a more common area of disease research over the past few decades, particularly for cancer patients as chemotherapies are known to damage healthy cells, whereas immunotherapy drugs assist the body’s immune system in combating the cancer without damaging normal cells.

There are multiple forms of Immunotherapies according to the American Society of Clinical Oncology, including CAR-T cell therapy, checkpoint inhibitors and cancer vaccines. CAR-T cell therapies involve modifying a person’s T-cells in the laboratory in a way that allows them to better fight off cancer cells. Checkpoint inhibitors are medications that are block proteins in cancer cells to prevent them from growing and reproducing. Cancer vaccines are similar to traditional vaccines, like the flu shot; they expose the body to an antigen, which triggers an immune response.

In a clinical trial where Rimiducid was used in combination with the BPX101 cancer vaccine to treat patients with advanced prostate cancer, immune upregulation and anti-tumor activity was observed, as well as prostate-specific antigen declines, objective tumor regressions and robust efficacy of post-trial therapy, all of which suggest this combination was a favorable treatment method.

Conclusion

As cancer research has progressed, researchers have found that a personalized approach to treatment is important and that treating cancer based on the mutations present often offers a more positive outcome. But in order for more treatments to become available, trials need to have an adequate number of participants.

For cancer patients who aren’t benefiting from standard treatment options, it is prudent to seek out studies related to the disease for a chance at getting healthy.

Other articles in this series:

Difficult-to-treat Cancers: Part 1 — What Now?
Difficult-to-treat Cancers: Part 2 — The Drug Discovery Process

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Dr. Harvey Berger founded ARIAD Pharmaceuticals, Inc. in 1991 and served as Chairman and Chief Executive Officer of the company until 2015. Today, he acts as the company’s Founder, Chairman and CEO Emeritus, in addition to his duties as the governing trustee at the Dana-Farber Cancer Institute. From 2017 to 2018, he served as the Executive Chairman at Medinol, Inc. Dr. Berger earned his A.B. degree in Biology at Colgate University and his medical degree from the Yale School of Medicine. He completed additional medical training at Yale-New Haven Hospital and Massachusetts General Hospital. Before founding ARIAD, Dr. Harvey Berger developed new medicines for various diseases, including lung cancer and Crohn’s Disease, and led the Research and Development Division at Centocor, Inc. from 1986 to 1991. He has also held teaching positions at Emory University, Yale University and the University of Pennsylvania. In 2013, he was awarded the Ernst & Young Entrepreneur of the Year Award in New England and the Gold Stevie Award for Executive of the Year, Pharmaceuticals. Dr. Berger currently resides in Palm Beach with his wife and two daughters.

Originally published at https://thedoctorweighsin.com on June 18, 2019.

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