Tree nut consumption, as well as a generally healthy lifestyle, significantly reduced the risk of cancer recurrence and death in patients with stage III colon cancer treated in the Cancer and Leukemia Group B (CALGB) 89803 trial, researchers reported at the 2017 ASCO Annual Meeting. Two subanalyses of this adjuvant therapy trial were presented in advance of the ASCO Meeting in an online press briefing for journalists. Experts weighing in on the CALGB 89803 trial are “impressed” with the results of these subanalyses (see Expert Point of View on this same page).

We can still get a lot of important information from negative clinical trials if secondary analyses are planned in advance.

— Richard L. Schilsky, MD

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CALGB (now Alliance) 89803 compared treatment with once-weekly fluorouracil and leucovorin to once-weekly irinotecan, fluorouracil, and leucovorin in 1,264 patients with stage III colon cancer between 1999 and 2001.¹ Most patients completed a self-administered semiquantitative questionnaire that captured diet and lifestyle habits midway through adjuvant therapy and again 6 months after completion of treatment. The primary analysis showed no difference in efficacy between the treatment arms, but subanalyses of the diet and lifestyle components are yielding interesting, and clinically applicable, results.

“Many secondary endpoints of this clinical trial have yielded important findings, even though the trial itself was negative for the primary treatment comparisons,” said Richard L. Schilsky, MD, Chief Medical Officer of ASCO. “One of the take-aways from this study is we can still get a lot of important information from negative clinical trials if secondary analyses are planned in advance.”

Key Findings

The analysis of nut consumption was based on a prospective, observational study of 826 patients, with disease-free survival as the primary endpoint.² Compared with patients who reported not eating nuts, those who consumed at least two servings of tree nuts per week (≥ 2 oz each)—which was 19% of the population—had a 42% reduced risk of recurrence (P = .03) and a 57% reduced risk of death (P = .01), according to Temidayo Fadelu, MD, a clinical fellow in medicine at Dana-Farber Cancer Institute, Boston.

Temidayo Fadelu, MD

“Numerous studies in the fields of heart disease and diabetes have shown the benefits of nut consumption, and we felt it was important to determine if these benefits could also apply to colorectal cancer patients,” Dr. Fadelu said. “Patients with advanced disease who benefit from chemotherapy frequently ask what else they can do to reduce their chances of recurrence or death, and our study is an important contribution to the idea that modifying diet and physical activity may be beneficial.”

The benefit was restricted to consumption of tree nuts, including almonds, walnuts, hazelnuts, cashews, and pecans, among others. In the group reporting one or more weekly servings (≥ 1 oz) of tree nut consumption, recurrence was reduced by 46% (P = .04) and death by 53% (P = .04). There was no associated reduction in recurrence or death among those who ate peanuts or peanut butter. According to the authors, peanuts and other legumes have a different metabolic composition than tree nuts. The benefit of tree nut consumption was consistent across the known factors that can influence cancer recurrence, including patient age, body mass index, gender, and common genomic tumor alterations.

Lifestyle Had Impact, Too

In another subanalysis of CALGB 89803, Erin Van Blarigan, ScD, of the University of California San Francisco, and colleagues reported that survivors of stage III colon cancer with the highest “healthy lifestyle scores” had a 42% lower risk of death and a trend toward reduced risk of recurrence.³

Erin Van Blarigan, ScD

Lifestyle was assessed twice as part of the trial, using validated surveys. Among 992 patients with stage III disease, the investigators applied a score that quantified adherence to the American Cancer Society’s (ACS) Nutrition and Physical Activity Guidelines. The components included body mass index; physical activity; and intake of vegetables, fruits, whole grains, and red or processed meats. Scores ranged from 0 to 6, with higher scores indicating healthier behaviors. Alcohol is included in the ACS Guidelines for cancer prevention but not for prevention of recurrence in cancer survivors. The researchers tested the score with and without alcohol consumption and adjusted the analysis for clinical, demographic, and lifestyle factors.

Over 7 years of median follow-up, 91 survivors (9% of the population) had the highest healthy lifestyle scores (5–6 points), whereas 262 survivors (26%) had the lowest (0–1 points). Those with the highest scores had a 42% lower risk of death from all causes (P = .01) and a trend toward improved disease-free survival (hazard ratio, 0.69; P = .03), compared with the 262 survivors with the lowest lifestyle scores (0–1 points), Dr. Van Blarigan reported.

Low to moderate consumption of alcohol was also protective. Optimal alcohol intake was considered up to 1 drink per day for women or 2 drinks per day for men. When including alcohol in the score, patients with the highest ACS scores vs the lowest had a 51% reduced risk of death (P = .002) and a 36% reduced risk of recurrence (P = .05), compared with those with the lowest ACS scores.

“Colon cancer patients with a healthy body weight who engaged in physical activity; ate a diet high in whole grains, vegetables, and fruits and low in red or processed meats; and drank moderate alcohol had longer recurrence-free and overall survival than patients who did not engage in these behaviors,” Dr. Van Blarigan stated.

Her research team is now conducting studies to evaluate the feasibility and acceptability of digital health lifestyle interventions, such as Fitbits, for colorectal cancer patients. “If our interventions are acceptable and useful to patients, we will test their impact on the risk of cancer recurrence and mortality in future studies,” she said. ■

Disclosure: Drs. Schilsky, Fadelu, and Van Blarigan reported no conflicts of interest.

References

1. Saltz LB, Niedzwiecki D, Hollis D, et al: Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: Results of CALGB 89803. J Clin Oncol 25:3456-3461, 2007.

2. Fadelu T, Niedzwiecki D, Zhang S, et al: Nut consumption and survival in stage III colon cancer patients: Results from CALGB 89803 (Alliance). 2017 ASCO Annual Meeting. Abstract 3517. Presented May 17, 2017, at a press briefing.

3. Van Blarigan E, Fuchs CS, Niedzwiecki D, et al: American Cancer Society Nutrition and Physical Activity Guidelines after colon cancer diagnosis and disease-free, recurrence-free, and overall survival in CALGB 89803 (Alliance). 2017 ASCO Annual Meeting. Abstract 10006. Presented May 17, 2017, at a press briefing.