Difficult-to-treat Cancers Pt 3: Recent Advances in the Treatment of Cancer
Cancer treatment has advanced significantly over the past few decades, due in large part to research performed by pharmaceutical companies.
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
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.
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.
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.
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:
- A Phase 2 Trial of Ponatinib in Philadelphia Chromosome-Positive Leukemias | NEJM. New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/nejmoa1306494. Accessed February 22, 2019.
- A Trial of TAK-788 (AP32788) in Non-small Cell Lung Cancer (NSCLC) — Full Text View. Search of: Spain — List Results — ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02716116. Accessed February 22, 2019.
- About Non-Small Cell Lung Cancer . American Cancer Society. https://www.cancer.org/content/dam/cancer-org/cancer-control/en/cancer-types/non-small-cell-lung-cancer-complete.pdf . Accessed February 22, 2019.
- Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer | NEJM. New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMoa1810171. Accessed February 22, 2019.
- Chawla SP, Staddon AP, Baker LH, et al. Phase II Study of the Mammalian Target of Rapamycin Inhibitor Ridaforolimus in Patients With Advanced Bone and Soft Tissue Sarcomas. Journal of Clinical Oncology. 2012;30(1):78–84. doi:10.1200/jco.2011.35.6329.
- Demetri GD, Mehren MV, Jones RL, et al. Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial. Journal of Clinical Oncology. 2016;34(8):786–793. doi:10.1200/jco.2015.62.4734.
- Editorial Board. Sarcoma, Soft Tissue: Statistics. American Society of Clinical Oncology. https://www.cancer.net/cancer-types/sarcoma-soft-tissue/statistics Accessed March 13, 2019.
- EluNIR Ridaforolimus Eluting Coronary Stent System — P170008. U.S. Food and Drug Administration. https://www.fda.gov/medicaldevices/productsandmedicalprocedures/deviceapprovalsandclearances/recently-approveddevices/ucm589536.htm Accessed March 13, 2019.
- FDA approves osimertinib for first-line treatment of metastatic NSCLC with most common EGFR mutations. U.S. Food and Drug Administration. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm605113.htm Accessed March 13, 2019.
- FDA Grants Approval of Pembrolizumab for Metastatic Melanoma. U.S. Food and Drug Administration. https://www.asco.org/advocacy-policy/asco-in-action/fda-grants-approval-pembrolizumab-metastatic-melanoma Accessed March 14, 2019.
- Gettinger SN, Bazhenova LA, Langer CJ, et al. Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies: a single-arm, open-label, phase 1/2 trial. Philosophical Transactions of the Royal Society B: Biological Sciences. https://doi.org/10.1016/S1470-2045(16)30392-8. Accessed February 22, 2019.
- Hazarika M, Jiang X, Liu Q, et al. Tasigna for Chronic and Accelerated Phase Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia Resistant to or Intolerant of Imatinib. Clinical Cancer Research. 2008;14(17):5325–5331. doi:10.1158/1078–0432.ccr-08–0308.
- How Do You Know If Treatment for Chronic Myeloid Leukemia Is Working? American Cancer Society. https://www.cancer.org/cancer/chronic-myeloid-leukemia/treating/is-treatment-working.html. Accessed February 22, 2019.
- Jabbour E, DerSarkissian M, Duh MS, et al. Efficacy of Ponatinib Versus Earlier Generation Tyrosine Kinase Inhibitors for Front-line Treatment of Newly Diagnosed Philadelphia-positive Acute Lymphoblastic Leukemia. Current neurology and neuroscience reports. https://www.ncbi.nlm.nih.gov/pubmed/29519619. Published April 2018. Accessed February 22, 2019.
- Jorge E. Cortes D-WK, Pinilla-Ibarz J, Coutre PDle, et al. Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood Journal. http://www.bloodjournal.org/content/early/2018/03/21/blood-2016-09-739086?sso-checked=true. Published January 1, 2018. Accessed February 22, 2019.
- Kandzari DE, Smits PC, Love MP, et al. Randomized Comparison of Ridaforolimus- and Zotarolimus-Eluting Coronary Stents in Patients With Coronary Artery Disease. Circulation. 2017;136(14):1304–1314. doi:10.1161/circulationaha.117.028885.
- Kayaniyil S, Hurry M, Wilson J, et al. Treatment patterns and survival in patients with ALK-positive non-small-cell lung cancer: a Canadian retrospective study. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5176386/. Published December 21, 2016. Accessed February 22, 2019.
- Keytruda Label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125514s034lbl.pdf Accessed March 14, 2019.
- Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. New England Journal of Medicine. 2018;378(5):439–448. doi:10.1056/nejmoa1709866.
- Mok TS, Wu Y-L, Ahn M-J, et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. New England Journal of Medicine. 2017;376(7):629–640. doi:10.1056/nejmoa1612674.
- NCI Drug Dictionary. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-drug/def/egfr-her2-inhibitor-ap32788. Accessed February 22, 2019.
- OA 05.05 Brigatinib in Crizotinib-Refractory ALK NSCLC: Updated Efficacy and Safety Results From ALTA, a Randomized Phase 2 Trial. NeuroImage. https://www.sciencedirect.com/science/article/pii/S1556086417310857. Published November 7, 2017. Accessed February 22, 2019.
- Osimertinib (TAGRISSO) U.S. Food and Drug Administration https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm549683.htm Accessed March 13, 2019.
- Ponatinib Approved for Treatment of Chronic Myeloid Leukemia : Oncology Times. LWW. https://journals.lww.com/oncology-times/pages/articleviewer.aspx?year=2017&issue=01250&article=00019&type=Fulltext. Accessed February 22, 2019.
- Rimiducid. National Center for Biotechnology Information. PubChem Compound Database. https://pubchem.ncbi.nlm.nih.gov/compound/ap1903#section=Top. Accessed February 22, 2019.
- Saglio G, Kim D-W, Issaragrisil S, et al. Nilotinib versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia. New England Journal of Medicine. 2010;362(24):2251–2259. doi:10.1056/nejmoa0912614.
- Should Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Be Intensive? Hematology Oncology. http://www.hematologyandoncology.net/archives/november-2016/should-treatment-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-be-intensive/. Accessed February 22, 2019.
- Solomon BJ, Besse B, Bauer TM, et al. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. The Lancet Oncology. 2018;19(12):1654–1667. doi:10.1016/s1470–2045(18)30649–1.
- Sonpavde G, McMannis JD, Bai Y, et al. Phase I trial of antigen-targeted autologous dendritic cell-based vaccine with in vivo activation of inducible CD40 for advanced prostate cancer. Current neurology and neuroscience reports. https://www.ncbi.nlm.nih.gov/pubmed/28608115. Published October 2017. Accessed February 22, 2019.
- Soria J-C, Ohe Y, Vansteenkiste J, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. New England Journal of Medicine. 2018;378(2):113–125. doi:10.1056/nejmoa1713137.
- Zhang S, Wang F, Keats J, et al. AP26113, a potent ALK inhibitor, overcomes mutations in EML4-ALK that confer resistance to PF-02341066 (PF1066). Cancer Research. http://cancerres.aacrjournals.org/content/70/8_Supplement/LB-298. Published April 15, 2010. Accessed February 22, 2019.
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.