Immunotherapy Is ASCO's Advance of the Year

Zosia Chustecka

February 04, 2016

Immunotherapy has been chosen as the "clinical cancer advance of the year" by the American Society of Clinical Oncology (ASCO) in its Clinical Cancer Advances 2016 report.

The report documents "important progress being made in clinical cancer research and highlights emerging trends in the field," the society explains.

"No recent advance has been more transformative than the rise of immunotherapy, particularly over this past year," writes ASCO president Julie Vose, MD, in the introduction.

Three immune checkpoint blockers are now available in the United States — ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda) —  and many others are in development. These drugs initially made an impact in advanced melanoma where patients previously had a life expectancy measured in months, but, in some cases, the new immunotherapies have extended that time to years.

Melanoma is "just the tip of the iceberg," Dr Vose writes. During 2015, clinical trials showed that the approach is effective in patients with other hard-to-treat cancers, including advanced lung, kidney, bladder, and head and neck cancers and Hodgkin's lymphoma.

Many other clinical advances — as detailed below — are highlighted in the report, which is now in its eleventh year.

This latest report was put together by 18 experts in a wide range of oncology subspecialties who review literature and presentations at major scientific meetings over a 1-year period (October 2014 to October 2015).

During that time period, the US Food and Drug Administration (FDA) approved 10 new cancer drugs, including two that were first-in-class therapies:

  • olaparib (Lynparza) for the treatment of advanced serous ovarian cancer with BRCA mutations. "This approval marked the first major improvement in the treatment of high-grade serous ovarian cancer in 30 years," the report authors note.

  • palbociclib (Ibrance) for the treatment of advanced breast cancer. With its new mechanism of action, palbociclib offers "an entirely novel treatment option" for estrogen-receptor-positive breast cancer, which is the most common type, accounting for two-thirds of cases, the report authors note.

Novel Approaches to Glioblastoma  

The report also highlights preliminary findings with a therapeutic cancer vaccine  rindopepimut (CDX-110) from a phase 2 trial in relapsed glioblastoma  (J Clin Oncol. 2015;33[suppl]:abstr 2009). In the trial, the vaccine was used together with bevacizumab (Avastin), which improved median survival to 12 months compared with 8.8 months in the bevacizumab-alone group. This vaccine targets glioblastoma with the EGFRvIII mutation (found in about one in four glioblastomas). A phase 3 trial of rindopepimut in patients newly diagnosed with this type of glioblastoma is under way ( identifier: NCT01480479).

Another novel approach uses a device that delivers tumor-treating fields (TTF), which patients wear on their head. The Optune device, also known as the NovoTTF-100A System, was previously approved for the treatment of recurrent glioblastoma, and in 2015, the FDA expanded its use to patients with newly diagnosed glioblastoma, after it showed improved survival when added to temozolomide.

This approach "is unlike other treatments for brain or other cancers, using so-called tumor-treating fields to stop the growth of rapidly dividing tumor cells," the authors write. However, they add that "it is unclear how well this new therapy that disrupts cell division will be adopted in routine practice. The effect of the device on patient quality of life remains controversial, because some patients have reported that wearing the device was too onerous."

Advances in Breast Cancer

Both of the advances in breast cancer highlighted by the report have already been covered in detail by Medscape Medical News.

One covers the use of ovarian suppression in young premenopausal breast cancer patients, and the results from the huge international trial, known as Suppression of Ovarian Function Trial (SOFT) (N Engl J Med. 2015;372:436-446), have already been hailed as practice-changing.

The other is the use of aromatase inhibitors as an alternative to tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy and radiation (J Clin Oncol. 2015;33[suppl]:abstr LBA500), which was hailed as potentially practice-changing.

Progress With Targeted Therapies

Hailed as a landmark was a study from the Lung Cancer Mutation Consortium that found that two-thirds of advanced lung adenocarcinomas harbor at least one such cancer-causing genetic change (JAMA. 2014;311:1998-2006). "This finding is important, because it suggests that most such patients may benefit from a targeted treatment that blocks the cancer-fueling protein," the report authors write, although they also point out that "only a minority of patients with lung cancer are candidates for targeted therapies at this time."

With regard to other advances with targeted therapies, the report notes that two such agents have recently found new therapeutic indications:

  • Ibrutinib (Imbruvica) was recently approved for use in Waldenstrom macroglobulinemia, becoming the first drug ever for the treatment of this rare lymphoma. Ibrutinib is already approved for use in mantle cell lymphoma and chronic lymphocytic leukemia.

  • Sorafenib (Nexavar) was recently shown to be active in acute myeloid leukemia. The drug, a tyrosine kinase inhibitor, is already approved for use in liver, kidney, and thyroid cancers.

Progress in Kidney and Stomach Cancer

In the treatment of kidney cancer, new studies showed that the standard second-line treatment, everolimus (an mTOR inhibitor), was outperformed by both the immunotherapy nivolumab, which improved overall survival, and the targeted therapy cabozantinib, which achieved the longest progression-free survival yet seen.

The data on nivolumab have since led to its approval in kidney cancer as a new indication.

In stomach cancer, a large trial (known as CLASSIC) showed that adjuvant chemotherapy with capecitabine and oxaliplatin decreased the risk for cancer recurrence after surgery by 42% (Lancet Oncol. 2014;15:1389-1396). The estimated 5-year survival rate was 78% in the chemotherapy group compared with 69% in the observation group.

New Drugs for Soft Tissue Sarcoma

The report highlights new results showing benefit with two news drugs in  common types of soft tissue sarcoma, liposarcomas and leiomyosarcoma.

These data have since led to the approval of both drugs — eribulin (Halaven), for use in the treatment of liposarcomas, in which it showed a survival advantage over dacarbazine, and trabectedin (Yondelis) for the treatment of both liposarcoma and leiomyosarcoma, for which it showed an improvements in progress-free survival (but not overall survival) compared with dacarbazine.

Advances in Surgery

The report highlights three advances in cancer surgery, which have already been reported in detail by Medscape Medical News, as follows:

  • Elective neck lymph node surgery has clear benefit for patients with early oral cancer, show results from a phase 3 study from India.

  • In rectal cancer, a comparison between laparoscopic surgery vs traditional surgery showed similar outcomes (N Engl J Med. 2015;372:1324-1332).

  • In breast cancer, the new technique of cavity shave margins halved the risk for additional surgery (N Engl J Med. 2015;373:503-510).

HPV Vaccine for Cancer Prevention

Under advances in cancer prevention, the report highlights the launch of Gardasil 9, the new nine-valent vaccine against human papillomavirus (HPV), which was introduced in late 2014 and offers protection against more strains of the virus than the two HPV vaccines already marketed, Gardasil and Cervarix.

The report also highlights "a major study" (J Natl Cancer Inst. 2015;107:djv086), which estimated that  widespread HPV vaccination with Gardasil or Cervarix could prevent 25,000 HPV-related cancers per year in the United States alone, and that the Gardasil 9 vaccine could prevent an additional 4000 cancer cases per year. These include the majority of invasive cervical, anal, oropharyngeal, and vaginal cancers, as well as some other genital cancers.

Immunotherapy "Clearly Stands Out"

"Although all research achievements highlighted in this report are remarkable, one area clearly stands out from the rest," the authors comment.

"Even for patients who have exhausted all traditional treatments, immunotherapy is able to halt cancer growth, often with only mild adverse effects," they note.

Among the clinical results achieved with checkpoint inhibitors, the report highlights the activity of nivolumab and pembrolizumab in lung cancer (now an approved indication for both drugs), as well as in other cancer types, and hints that the next drug in this class could be atezolizumab, which has shown benefit in bladder cancer, as well as other cancer types.

Another immunotherapy approach — chimeric antigen receptor (CAR) T-cell therapy — has shown promise in patients with hematological malignancies. But the report warns that the results so far have come from studies that "were small and limited to patients with hard-to-treat cancers."

"It is not yet clear if CAR T-cell therapy will have broader use in the future," the authors comment. As the approach can cause considerable toxicities, it is currently administered only in specialized clinical centers.

The report also highlights a unique new immunotherapy, the antibody blinatumomab (Blincyto), which was recently approved for use in an uncommon but aggressive type of acute lymphoblastic leukemia (ALL), the Philadelphia chromosome-negative precursor B-cell ALL.

"Although more research is needed to determine whether blinatumomab can improve survival compared with standard chemotherapy, it seems that immunotherapy will play a role in the treatment of ALL," the authors write. Future directions include exploring use of blinatumomab earlier in the course of the disease and in combination with other therapies.


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