Drug Shows Promise for Subset of Stage III Colon Cancer Patients

This article describes the results of a clinical trial—a research study with volunteer patients. The trial tested adding a third drug to a standard two-drug chemotherapy treatment for colorectal cancer. The standard treatment consists of the drugs fluorouracil and leucovorin. It is given to patients after tumor-removal surgery to keep the cancer from coming back (recurrence). In the trial, a third drug called irinotecan was added. The researchers found that stage III patients whose tumors tested positive for a genetic change called CIMP benefitted from the irinotecan addition. Stage III CIMP-negative patients did not.

“When added to the standard chemotherapy treatment — fluorouracil and leucovorin — adjuvant irinotecan therapy improved overall survival rates for patients with the CpG island methylator phenotype (CIMP). CIMP is seen in about 10 to 20 percent of colorectal cancers. Patients with CIMP-negative tumors, however, exhibited significant harm from the addition of irinotecan — overall survival was 68 percent compared with 78 percent for those receiving the standard treatment alone.

“Our results serve as an example that the molecular characterization of individual tumors may help to determine the most appropriate treatment for patients with colon cancer,” said lead study author Stacey Shiovitz, MD, from the department of medicine, University of Washington, Seattle, WA, and the clinical research division of Fred Hutchinson Cancer Research Center, also in Seattle. “Based on our findings, identification of a tumor’s CIMP status should play a greater role in the clinical setting.”


No Disease-Free Survival Benefit of Adjuvant Zoledronic Acid in High-Risk Patients With Early Breast Cancer

The gist: Some people with breast cancer are treated with adjuvant therapy after surgery to keep their cancer from returning. A recent study with volunteer patients tested the effectiveness of adjuvant therapy with zoledronic acid. It was found that the treatment did not, in fact, increase the amount of time that high-risk, early-stage breast cancer patients lived without their cancer returning. However, it did reduce the risk of bone metastases.

“In the open-label phase III AZURE trial reported in The Lancet Oncology, Coleman et al found that adjuvant zoledronic acid treatment in patients with high-risk early-stage breast cancer provided no overall disease-free survival benefit. A reduction in bone metastases was observed, and women who were > 5 years postmenopause appeared to derive a disease-free survival benefit…

“In the trial, 3,360 women with stage II or III breast cancer from 174 centers in seven countries were randomly assigned between September 2003 and February 2006 to receive standard systemic adjuvant therapy with or without intravenous zoledronic acid. Zoledronic acid was given at 4 mg every 3 to 4 weeks for six doses, every 3 months for eight doses, and every 6 months for five doses, for a total of 5 years of treatment. The primary endpoint was disease-free survival in the intent-to-treat population…

“Median follow-up was 84 months. Compared with the control group, the zoledronic acid group had similar disease-free survival (adjusted hazard ratio [HR] = 0.94, P =  .30), invasive disease-free survival (HR = 0.93, P = .22), overall survival (HR = 0.93, P =  .37), and risk of distant recurrence (HR = 0.93, P = .29). Patients in the zoledronic acid group had reduced risk of bone metastases as a first event (HR = 0.78, P = .020) and at any time during follow-up (HR = .81, P = .022).”


Frailty Predicts Noninitiation but Not Discontinuation of Adjuvant Hormonal Therapy in Older Women With Breast Cancer

Editor’s note: It can be useful to understand why cancer patients and their doctors make certain treatment decisions. In a new study, scientists investigated how frailty affects decisions about hormonal therapy for older women with breast cancer. The study involved women aged 65 years or older who had invasive non-metastatic breast cancer. The researchers found that frail patients were less likely to start adjuvant hormonal therapy (treatment to keep cancer from returning after it was surgically removed). But frailty did not seem to affect whether or not a woman chose to stop hormone therapy treatment early.

Excerpt:

“In a study reported in the Journal of Clinical Oncology, Sheppard et al found that frailty was a significant predictor of not starting adjuvant hormonal therapy in breast cancer patients aged ≥ 65 years, but was not predictive of discontinuation of treatment.

“Study details: The study was performed in a prospective cohort (Cancer and Leukemia Group B [CALGB] 369901) of 1,288 women aged ≥ 65 years diagnosed with invasive nonmetastatic breast cancer recruited from 78 sites between 2004 and 2011. Of these, 1,062 had estrogen receptor–positive tumors.

“Interviews were conducted at baseline, 6 months, and every year up to 7 years. Initiation of hormone therapy was identified from records and discontinuation was identified by self-report. Baseline frailty was measured using a validated 35-item scale, with patients being characterized as prefrail, frail, or robust.”


Continued Event-Free Survival Benefit of Neoadjuvant/Adjuvant Trastuzumab in HER2-Positive Locally Advanced Breast Cancer

The gist: A recent clinical trial found that the drug trastuzumab (Herceptin) improves survival and lowers the risk of recurrence for women with HER2-positive, locally advanced breast cancer. Patients in the trial received Herceptin as part of both neoadjuvant (before surgery) and adjuvant (after surgery) treatment. The researchers followed the patients for five years after treatment.

“As reported by Gianni et al in The Lancet Oncology, long-term follow-up of women with HER2-positive locally advanced breast cancer receiving neoadjuvant chemotherapy alone vs with neoadjuvant and adjuvant trastuzumab (Herceptin) in the phase III NOAH trial has shown continued event-free survival benefit of trastuzumab treatment and a strong association of event-free survival with pathologic complete response rate in trastuzumab recipients.

“In this open-label trial, 235 women with HER2-positive locally advanced or inflammatory breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (n = 118) or with 1 year of trastuzumab given concurrently with neoadjuvant chemotherapy and continued after surgery. (A parallel group with HER2-negative disease received neoadjuvant chemotherapy alone; outcomes in this group are not reported here.)”


Phase II Randomized Trial Comparing High-dose Interferon Alfa-2b with Temozolomide plus Cisplatin as Systemic Adjuvant Therapy for Resected Mucosal Melanoma

“Mucosal melanoma is rare and associated with extremely poor prognosis. However, standard adjuvant therapy for mucosal melanoma has not been established. We conducted a randomized phase II clinical trial in resected mucosal melanoma (MM) patients to compare the efficacy and safety of high-dose IFN-α2b (HDI) and temozolomide-based chemotherapy as adjuvant therapy.”


Engineered SIRPα Variants as Immunotherapeutic Adjuvants to Anticancer Antibodies

CD47 is an antiphagocytic signal that cancer cells employ to inhibit macrophage-mediated destruction. Here, we modified the binding domain of human SIRPα, the receptor for CD47, for use as a CD47 antagonist. We engineered high-affinity SIRPα variants with approximately 50,000-fold increased affinity for human CD47 relative to wild-type SIRPα. As high-affinity SIRPα monomers, they potently antagonized CD47 on cancer cells but did not induce macrophage phagocytosis on their own.


Engineered SIRPα Variants as Immunotherapeutic Adjuvants to Anticancer Antibodies

CD47 is an antiphagocytic signal that cancer cells employ to inhibit macrophage-mediated destruction. Here, we modified the binding domain of human SIRPα, the receptor for CD47, for use as a CD47 antagonist. We engineered high-affinity SIRPα variants with approximately 50,000-fold increased affinity for human CD47 relative to wild-type SIRPα. As high-affinity SIRPα monomers, they potently antagonized CD47 on cancer cells but did not induce macrophage phagocytosis on their own.


Engineered SIRPα Variants as Immunotherapeutic Adjuvants to Anticancer Antibodies

CD47 is an antiphagocytic signal that cancer cells employ to inhibit macrophage-mediated destruction. Here, we modified the binding domain of human SIRPα, the receptor for CD47, for use as a CD47 antagonist. We engineered high-affinity SIRPα variants with approximately 50,000-fold increased affinity for human CD47 relative to wild-type SIRPα. As high-affinity SIRPα monomers, they potently antagonized CD47 on cancer cells but did not induce macrophage phagocytosis on their own.