A mix of traditional and customized acupuncture techniques proved effective in reducing pain and stiffness associated with aromatase inhibitor (AI) therapy in women with early-stage breast cancer, according to data from a randomized phase III trial presented at the 2017 San Antonio Breast Cancer Symposium (SABCS).

Investigators said a 12-week intervention program demonstrated the value of the therapy to help relieve symptoms that may cause patients to skip or stop treatments. “We have heard throughout this conference about the efficacy of AIs for women with hormone-sensitive breast cancer. It works both in the adjuvant setting in women with metastatic disease, and for the prevention of breast cancer.” said Dawn L. Hershman, MD, MS, leader of the Breast Cancer Program at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Columbia University Medical Center.

“But we also know that it doesn’t work if you don’t take it, and noncompliance is a major problem amongst women taking hormonal therapy,” Hershman said in discussing the research team’s findings during an SABCS press briefing.

Hershman acknowledged that noncompliance can be multifactorial, but one of the main reasons patients discontinue treatment is because of adverse effects and, in particular, joint pain and stiffness. “[Therefore,] we were interested in a nonpharmacologic modality for assessing whether or not we could control these symptoms.”

Small studies have suggested acupuncture may be beneficial in treating AI-associated arthralgia; however, these findings are not consistent across all trials. To test this theory across multiple measures, the researchers conducted the multicenter, randomized phase III trial designed to evaluate the efficacy of acupuncture in reducing AI-related joint symptoms over a 24-week period.

Patients reported their pain before, during, and after acupuncture or no treatment using the Brief Pain Inventory (BPI)-Short Form, a self-administered questionnaire of 14 items, to evaluate the severity of pain on a scale of 0 to 10, with higher scores indicating more pain and an increased impact on daily functioning.

To be eligible, women were required to have hormone receptor-positive, stage I to III breast cancer; be taking a third-generation AI for at least 30 days; report a score of 3 or more of BPI worst pain; have symptoms that started or progressed since starting AI therapy; have received no opioids, corticosteroids, or alternative/physical therapy for joint pain for 28 days prior to registration; and have had no prior acupuncture treatment for AI-associated joint pain.

Researchers randomized 226 patients 2:1:1 to the following treatment arms:

True acupuncture: standard traditional Chinese medicine point prescription, a 30- to 45-minute session including a full body, auricular, and joint-specific acupuncture protocol tailored to the most painful joints (n = 110)

Sham acupuncture: shallow needle insertion with thin, short needles at 4 standardized non-acupuncture points (n = 59)

Waitlist control: patients were under the impression they would receive true acupuncture following the 24-week trial (n = 57).

Improved joint pain score after 6 weeks served as the primary endpoint. The researchers also evaluated maintenance acupuncture efficacy from weeks 6 through 12, followed by an additional 12-week follow-up. True acupuncture and sham treatments included twice-weekly sessions for 6 weeks followed by 1 session per week for 6 more weeks.

Patients were a median 60.7 years of age, and had been receiving AI therapy for a median of 1.1 years. Forty-four women previously received acupuncture therapy for other conditions (19%). At baseline, women reported BPI worst pain scores of 6.84, 6.55, and 6.48 in the true, sham, and waitlist arms, respectively.

After 6 weeks of treatment, mean BPI worst pain scores were 0.92 points lower in the true acupuncture arm (95% CI, 0.20-1.65; 

= .01) compared with the sham arm, and 0.96 points lower than the waitlist control arm (95% CI, 0.24-1.67;

Additionally, the true acupuncture arm demonstrated a greater proportion of patients reporting clinically meaningful reductions in BPI worst pain of 2 points or more (58%), compared with the sham (31%;

 < .004). According to a linear mixed model, these data remained statistically significant at 24 weeks.

The true acupuncture arm also outperformed the sham and waitlist arms in additional 6-week endpoints, including more favorable BPI scores for average pain, pain interference, pain severity, and worse stiffness. Similarly, these results were maintained after 24 weeks according to a linear mixed model.

“We have shown consistently, with multiple measures assessing pain and stiffness, that true acupuncture generated better outcomes than either control group in a large multicenter randomized controlled trial,” Hershman said. “And transitioning from twice-a-week to once-a-week acupuncture maintained the effect of the intervention.”

Grade 1 bruising appeared to be the only significant adverse event reported among true (47%) and sham acupuncture patients (25%; P = .01).

“Acupuncture provides a nonpharmacologic option that can improve symptoms and possibly increase AI adherence as well as subsequent breast cancer outcomes,” Hershman said. “For patients who are reluctant to take a prescription medication that can result in other side effects, acupuncture provides a safe and effective alternative. Identification of nonopioid options for pain control is a public health priority.”

Hershman also noted the added benefits derived from the cost of the 12-week, 18-session intervention, which amounted to approximately $1250 ($65-$75 per session).

“We feel there is now sufficient evidence to support insurance coverage of acupuncture for AI arthralgia, “she said.

Hershman DL, Unger JM, Greenlee H, et al. Randomized blinded sham- and waitlist-controlled trial of acupuncture for joint symptoms related to aromatase inhibitors in women with early stage breast cancer (S1200). Presented at: 2017 San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio, TX. Abstract GS4-04. abstracts2view.com/sabcs/view.php?nu=SABCS17L_503&terms=

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A mix of traditional and customized acupuncture techniques proved effective in reducing pain and stiffness associated with aromatase inhibitor (AI) therapy in women with early-stage breast cancer.

Acupuncture Reduces AI-Associated Joint Pain in Women with Breast Cancer

Shortening the intervals between chemotherapy cycles or administering the drugs sequentially reduced early-stage breast cancer recurrence and mortality compared with standard dosing techniques, according to meta-analysis results presented at the 2017 San Antonio Breast Cancer Symposium.

The 2 most commonly used chemotherapy regimens, anthracycline- and taxane-based combinations, are proven to reduce mortality among women with early breast cancer by one-third. However, pivotal trials have demonstrated there may be an added benefit from dose intensification.

“We are still trying to find ways in improving how we deliver this chemotherapy,” said Richard Gray, MSc, professor of medical statistics in the Nuffield Department of Population Health at University of Oxford in the United Kingdom. “The rationale for this is if you look at computer models about how cancer cells get knocked back by chemotherapy and then regrow again, it seems if you increase dose intensity, you might be more likely to eradicate more cancer cells.” Gray and colleagues collected data from the Early Breast Cancer Clinical Trialists' Collaborative Group (EBCTCG), a worldwide collaboration designed to assess the long-term benefits and adverse effects associated with a variety of treatment options for patients with early-stage breast cancer. In particular, the researchers focused on whether increasing the dose intensity of chemotherapy would induce superior outcomes compared with standard chemotherapy regimens. Dose intensification trials used the same chemotherapy agents at the same doses as in standard regimens but patients received the drugs every 2 weeks versus every 3 weeks, resulting in an average weekly dose that is 1.5 times higher. Additionally, doses may be intensified by administering chemotherapy in sequence rather than concurrently.

Individualized patient data were analyzed from 25 trials, including the following:

Seven randomized trials, designed to test chemotherapy given every 2 weeks compared with every 3 weeks (n = 10,004)

Nine randomized trials, which tested sequential versus concurrent anthracycline- and taxane-based chemotherapies (n = 11,533)

The researchers evaluated reductions in disease recurrence and morality, as well as safety.

Patients who received chemotherapy every 2 weeks appeared 17% less likely to experience disease recurrence (rate ratio [RR], 0.83; 95% CI, 0.76-0.91; P = .00004), with a 14% reduction in the risk of death from breast cancer within 10 years (RR, 0.86; 95% CI, 0.77-0.95; P = .004), compared with patients who received the same treatment every 3 weeks.

Similarly, patients who received sequential chemotherapy every 3 weeks demonstrated a 13% reduction in the risk for disease recurrence (RR, 0.87; 95%CI, 0.80-0,94; P = 0006), and were 11% less likely to die from breast cancer within 10 years (RR, 0.89; 95% CI, 0.80-0.99; P = .03) compared with patients who were treated with concurrent therapy ever 3 weeks.

In a pooled analysis of the 25 identified trials, patients who received dose-intensification therapy showed a 15% reduction in the risk for disease recurrence (RR, 0.85; 95% CI, 0.81-0.89; P <.00001) and a 13% reduction in the risk for breast cancer mortality (RR, 0.87; 95%CI, 0.82-0.92; P <.00001) compared with those who received standard therapy.

“This reduction [in mortality] may seem a very marginal difference, but when you think that we have already made a lot of improvements with chemotherapy … you can then [administer] dose intensification, and a one-third reduction comes to almost half a reduction in breast cancer mortality,” Gray said. “These increments have made a really big difference in breast cancer survival by identifying little ways of improving what we are doing already.”

“Whichever way these trials are achieving dose intensification they seem to be finding benefit in fewer recurrences,” Gray added. “This is quite remarkable how consistent all of these different approaches work in showing fewer recurrences and breast cancer mortalities.”

Despite concerns about safety, the researchers also found few additional adverse events among those who received dose-intense treatments, including fewer patients who died from non-breast cancer causes.

Virginia G. Kaklamani, MD, co-director of the symposium and leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center, commended these findings, noting the win-win therapeutic approach. “The beauty of these approaches is [we are using the] exact same drugs and similar doses. It is just the schedule that changes,” she said. “What is interesting is we used to give chemotherapy over 6 months and with this approach we can give it over 4 months. The patients prefer it, and the toxicity can be less. So, everyone wins here.”

Moving forward, Gray noted the need for more trials to be conducted.

“The problem is, often, that we have not looked well enough at simple questions on how long to give chemotherapy, which is really important for women to get more benefit without extra toxicity,” he said. “What we need is more trials to test simple concepts, very simple bread-and- butter questions that should be addressed more often in clinical trials.”

Gray R, Bradley R, Braybrooke J, et al; for the EBCTCG. Increasing the dose density of adjuvant chemotherapy by shortening intervals between courses or by sequential drug administration significantly reduces both disease recurrence and breast cancer mortality: An EBCTCG meta-analysis of 21,000 women in 16 randomised trials. Presented at: 2017 San Antonio Breast Cancer Symposium; Dec. 5-9; Atlanta. Abstract GS1-01. abstracts2view.com/sabcs/view.php?nu=SABCS17L_1396&terms=

Shortening the intervals between chemotherapy cycles or administering the drugs sequentially reduced early-stage breast cancer recurrence and mortality compared with standard dosing techniques.

Kristie L. Kahl

Articles

Acupuncture Reduces AI-Associated Joint Pain in Women with Breast Cancer

Alternative Chemotherapy Dosing Strategies Improve Breast Cancer Outcomes