Updates from the American Society of Clinical Oncology's Annual Meeting

CURESummer 2014
Volume 13
Issue 2

Cancer researchers and clinicians gathered in Chicago to discuss advances in cancer research.

The American Society of Clinical Oncology (ASCO) hosted its 50th annual meeting in Chicago from May 30 to June 3, bringing together more than 34,600 cancer researchers, physicians, industry professionals, advocates and survivors to report on advances in cancer screening, diagnosis, treatment and prevention. For more coverage of the conference, visit our conference page.

Hormone therapy is a standard treatment for men with advanced prostate cancer, but when the cancer progresses, chemotherapy is often used. Researchers questioned whether chemotherapy would improve survival if it was given earlier, during hormone therapy and before the cancer becomes resistant. The investigators found that combining the chemotherapy drug docetaxel early in treatment with hormone therapy improved survival by 10 months in patients with newly diagnosed, stage 4 hormone-sensitive prostate cancer.

The trial studied 790 men, with about two-thirds having extensive metastases. Median overall survival improved from 44 months to 57.6 months, and men with extensive metastases saw an improvement from 32.2 months to 49.2 months—a 17-month improvement. Overall survival in men with less extensive metastases is not yet known, but researchers are continuing to follow the group to determine whether there is a benefit from the combination.

The addition of chemotherapy resulted in one treatment-related death out of 397 participants. Participants also reported neuropathy as well as low white blood cell counts and fever, which could result in increased infection risk.

“The benefit in patients with a high volume of metastases is clear and justifies the treatment burden,” said Christopher Sweeney, the study’s lead author and an oncologist at Dana-Farber Cancer Institute in Boston. “Longer follow-up is required for patients with low volume metastatic disease.”

Michael Morris, an oncologist at Memorial Sloan Kettering Cancer Center in New York, provided commentary after the presentation and noted the large jump in survival is practically unheard of in this patient population. “If you look at every drug that prolongs survival in castration-resistant disease, none even come close in terms of survival prolongation to 17 months. Our best therapies in metastatic castration-resistant disease are less than a third of that for the high-volume patients in [the] ECOG3805 [study],” he said, noting that the combination uses a generic, older chemotherapy at a fraction of the cost of newer therapies. —Elizabeth Whittington

After a long period with little progress, a number of new therapies for treating melanoma have been highlighted at recent ASCO annual meetings, and this year was no exception. Hoping to build on the successful introduction of the immunotherapy drug Yervoy (ipilimumab), researchers investigated whether it would be effective in treating patients with earlier-stage disease who remained at high risk of recurrence after surgery. Yervoy was approved in 2011 for treating inoperable, late-stage melanoma.

In the phase 3 study, 951 participants whose stage 3 melanoma had been surgically treated were randomized to receive Yervoy or a placebo. Alexander Eggermont, the study’s lead author, reported that after 2.7 years, Yervoy was shown to reduce the risk of recurrence by about 25 percent compared with placebo. However, participants experienced considerable side effects, including inflammation of the colon, thyroid and pituitary gland, as well as skin rash. In fact, more than half (52 percent) of participants discontinued the treatment because of side effect severity, and five treatment-related deaths occurred.

Two other immune-checkpoint inhibitor drugs—pembrolizumab and nivolumab—showed success in early phase 1 trials. In a study of 411 participants with advanced melanoma, pembrolizumab proved effective in participants who had received multiple prior therapies, including Yervoy, as well as those whose metastatic disease was newly diagnosed. Overall, 34 percent of participants experienced tumor response, with an estimated survival rate of 69 percent at one year. Twelve percent of participants experienced serious treatmentrelated side effects, with 4 percent dropping out because of the severity of the side effects. Pembrolizumab, an antibody that blocks a pathway on T-cells, previously received a breakthrough therapy designation for treating inoperable, late-stage illness, and was granted a priority review under the FDA’s accelerated approval program in May.

In a third study, researchers investigated whether combining the antibody drug nivolumab with Yervoy would improve long-term survival for patients with advanced melanoma. Results showed that 41 percent of the 53 participants responded to the treatment, with 17 percent experiencing complete remissions. The median survival rate was about 40 months, and side effects were considered manageable and reversible. —Jon Garinn

While non-small cell lung cancer (NSCLC) is considered a hard-to-treat cancer, three studies presented at ASCO may help researchers decide on the best treatment for individual patients, as well as uncovering possible new approaches for squamous cell lung cancer, a type of NSCLC that hasn’t benefited from recent advances in targeted therapy.

Patients whose cancer has progressed or relapsed after initial therapy typically experience a median survival of about seven to nine months. In the REVEL study, patients who received ramucirumab with standard docetaxel lived a median of 10.5 months compared with patients receiving docetaxel alone (9.1 months). Researchers noted that while the survival difference is incremental, this is the first trial in a decade that has shown a survival advantage in second-line therapy for NSCLC.

In one of the largest studies ever conducted in squamous cell lung cancer, necitumumab, an investigational agent that targets the EGFR mutation in certain lung cancers, also improved survival, albeit modestly. The drug was tested in 1,093 participants who had stage 4 squamous cell NSCLC. The patients who received necitumumab with standard chemotherapy experienced longer median survival (11.5 months compared with 9.9 months with standard chemotherapy), as well as longer progression-free survival. Because there are few options for this type of NSCLC, necitumumab is expected to be under Food and Drug Administration review for approval by the end of the year.—Elizabeth Whittington

Preventing early menopause and preserving fertility are common concerns among women undergoing chemotherapy for breast cancer. A phase 3 trial found that adding goserelin, a hormone-suppressing drug, to standard chemotherapy could help prevent early menopause and preserve fertility in early-stage, hormone receptor-negative breast cancer patients.

In the study, premenopausal women who were given goserelin with a cyclophosphamidecontaining chemotherapy were less likely to have ovarian failure than women who received chemotherapy alone. The addition of goserelin also seemed to improve the chances of a successful pregnancy. Goserelin is a luteinizing hormonereleasing hormone (LHRH), which suppresses ovarian function for a short time. Researchers hypothesize that this action protects the follicles, small structures inside the ovaries in which eggs form, from chemotherapy damage. Side effects, such as hot flashes, were similar to those of menopause.

“Now we should offer all premenopausal women with ER-negative breast cancer about to embark on chemotherapy the option to take the goserelin to prevent sudden menopause from the chemotherapy and all the symptoms that come with it,” says senior study author Kathy Albain, a professor at Loyola Medicine and CURE advisory board member.

A still inconclusive finding in the study was that women who received goserelin were also 50 percent more likely to survive without disease recurrence four years after treatment compared with those who did not receive goserelin. “This is an intriguing and unexpected finding, and possibly is due to interactions of the shot with the breast cancer cells in some way,” Albain says. “For example, breast cancer cells can have LHRH receptors on the surface, which is the target for goserelin. There are other theories. The good news about these findings is that it is safe, and if anything, breast cancer survival is better.”—Lena Huang

Thyroid cancer is considered highly curable, but for 5 to 15 percent of patients, the standard treatments of surgery and radioactive iodine (RAI) therapy aren’t enough to keep the disease from advancing. Researchers announced results of a phase 3 trial of the oral kinase inhibitor lenvatinib that could provide another treatment option similar to Nexavar (sorafenib), which was approved by the Food and Drug Administration (FDA) for treatment-resistant tumors in 2013.

In the study, 392 participants whose disease had progressed within 13 months of previous treatment were randomized to receive lenvatinib or a placebo. Researcher Martin Schlumberger, professor of oncology at the University Paris Sud in Paris, France, said 65 percent of participants who took lenvatinib experienced tumor reduction, compared with 2 percent who received placebo. Moreover, the time to disease progression was more than 18 months for participants on the lenvatinib arm, compared with almost four months for those on placebo. However, 97 participants who took lenvatinib experienced some adverse events, primarily high blood pressure, diarrhea, decreased appetite, fatigue and nausea. —Jon Garinn

Adjuvant therapies are given after primary treatment, usually surgery, to reduce the risk of cancer recurrence in many patients. Findings from two large-scale studies on adjuvant therapies in breast cancer were presented at ASCO, signifying the importance of these treatments.

Early findings were released in a joint analysis of two phase 3 studies (TEXT and SOFT), which found Aromasin (exemestane) slightly more effective than tamoxifen when given with ovarian function suppression in preventing recurrences in premenopausal patients with hormone receptor-positive breast cancer. Researchers found about a 4 percent difference in recurrence risk over four years. However, investigators are awaiting final data from the tamoxifen-only arm, which are anticipated to be presented at the San Antonio Breast Cancer Symposium in December.

The second phase 3 study (ALLTO) examined adding Tykerb (lapatinib) to or after adjuvant Herceptin (trastuzumab) for patients with early-stage, HER2-positive breast cancer. These multidrug regimens did not prove more effective than the standard treatment of Herceptin alone. Researchers found no statistically significant difference in treatments after four and a half years. —Lena Huang