By Alfred I. Neugut

Each June, the American Society of Clinical Oncology holds its annual meeting in Chicago, one of only two or three cities in the U.S. that has sufficient convention and hotel facilities to accommodate the over 40,000 attendees. At this meeting the most important advances of the year, which will impact how cancer is treated going forward, are presented. I did not attend in person, but will highlight some of the key studies (in my view):

• Gliomas, adult malignant brain tumors, have been one of the most resistant types of malignancies to therapeutic advances. But the term covers an umbrella of subtypes. The contemporaneous subtyping of glial (the cell of origin of these tumors) malignancies primarily focuses on their grade (histologic differentiation) and whether they contain a mutation for the gene for an enzyme called IDH (isocitrate dehydrogenase 1 or 2), a mutation that is present in about 80% of glial malignancies. Tumors that are low-grade and have these mutations (the most common malignant brain tumor in those under age 50) are still not curable but have significantly better prognoses, ranging up to 10 years; these tumors fall into categories known as astrocytoma and oligodendroglioma. The mainstays of treatment, as for all gliomas, are surgery and radiotherapy. At ASCO this year, a study from Memorial Sloan-Kettering randomized 331 such patients to receive either oral vorasidenib or a placebo in a double-blind randomized trial. The study outcome at a median follow-up of only 14 months was disease progression which occurred at a median of 27.7 months for the intervention group versus 11.1 months for the placebo group. There were no deaths in either arm of the trial. This illustrates how eager the oncology community is for therapeutic options for malignant brain tumors, if so much emphasis is placed on a drug when so far no survival benefit has yet been demonstrated.
• Continuing in the realm of poor-risk tumors, another study of interest was reported from Norway regarding pancreatic cancer. Roughly 80% of patients will have advanced unresectable disease at diagnosis and, if they are in good physical condition, will be advised to undergo chemotherapy. At this time, perhaps the leading regimen is one known as FOLFIRINOX, a difficult regimen but probably the most effective one known (FOLinic acid, 5-Fluorouracil, IRINotecan, OXaliplatin). With FOLFIRINOX, the median survival in trials runs just about one year. An effort has been made to utilize this regimen in the neoadjuvant setting—to administer it in advance for the 20% of patients with resectable pancreatic cancer in order to shrink their tumors in advance of surgery and ameliorate their survival outcomes. A randomized trial was reported at ASCO in which 1,140 patients were randomized to FOLFIRINOX in advance of surgery or to surgery followed by adjuvant FOLFIRINOX. The endpoint was survival at 18 months. Neoadjuvant therapy did not improve survival. My own thought on this is that it is not a surprising finding since for almost all tumors the benefits of adjuvant therapy are similar if the therapy is administered in advance or after surgery.
• One of the recent trends in oncology has been an effort to reduce the length of administration of effective chemotherapy regimens. In that light, a study from Padua, Italy, investigated the use of trastuzumab (Herceptin) as adjuvant therapy in women with HER2-positive breast cancer. The standard of care is that, following surgery and in conjunction with other modes of adjuvant therapy, such women normally receive one year of Herceptin. The study reported at ASCO described a trial in which 2,500 women were randomized to nine weeks of Herceptin versus the standard one year of Herceptin. With a follow-up of six years, the disease-free survival was similar in the two groups.
• In another study from Memorial Sloan-Kettering, investigators reported a randomized trial of neoadjuvant treatment for localized rectal cancer. The standard of care has been to treat patients with combined chemotherapy and radiotherapy. Probably 15 or 20 years ago, there were selected patients who were unable to undergo radiation therapy because they had undergone RT previously, usually for prostate cancer, and one cannot receive RT twice to the same anatomic site. As a result, these patients underwent chemotherapy in the absence of RT. Lo and behold, they did fine. This experience led the investigators to conduct larger studies further exploring the use of chemotherapy alone in the management of rectal cancer, and it seemed to do well. The ultimate result was this study, a multicenter randomized trial in which 1,194 patients with localized rectal cancer were randomized to either chemotherapy alone or the usual chemotherapy combined with radiotherapy, both followed by surgery. For both groups, disease-free and overall survival were similar, suggesting that for localized rectal cancer one can safely dispense with radiation therapy, at least from a survival point of view. Of course, as I have mentioned previously in these articles, RT for rectal cancer does not impact survival so these results are not surprising—the goal of RT is to prevent local recurrence. This endpoint was unfortunately not mentioned in the article and would require longer follow-up to ascertain. The article also did not report the rate of permanent ostomies for the two arms of the trial, another important goal of RT.
  

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Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].

This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.