Study suggests careful patient selection can help predict who will best derive treatment benefit

Adjuvant chemotherapy extended median overall survival (OS) in selected elderly patients with estrogen receptor-positive, node-positive breast cancer despite the presence of multiple comorbidities, a retrospective study found.

In a cohort of 592 patients in a matched analysis set, median OS was 33% longer in the adjuvant chemotherapy group at a Hazard Ratio (HR) of 0.67 (95% CI, 0.48-0.93; P=0.02) compared with no chemotherapy after adjusting the analysis for confounding risk factors, Nina Tamirisa, MD, The University of Texas MD Anderson Cancer Center in Houston, Texas and colleagues reported in JAMA Oncology.

More patients who received chemotherapy received other adjuvant treatments as well, including endocrine therapy at 88.3% compared with 75.4% for those who did not receive chemotherapy (P=0.01) and radiation therapy at 67.4% compared to 43.5% for non- chemotherapy recipients (P<0.001), investigators noted.

“[T]hese findings suggest that physicians carefully selected patients likely to derive treatment benefit from adjuvant chemotherapy based on certain unmeasured variables,” Tamirisa and colleagues observed.

“Our study found that carefully selected patients within this subset of the population may benefit from additional adjuvant treatment, highlighting the importance of accurately estimating life expectancy in patients with multiple comorbidities,” they added.

A total of 1,592 elderly patients with multiple comorbidities and estrogen receptor-positive, node-positive breast cancer were identified from the U.S. National Cancer Database.

“Patients were included if they had a Charlson/Deyo comorbidity score of 2 or 3,” investigators noted.

The mean age of the cohort was 77.5 and 96.9% were female.

Of the 1592 patients included in the initial non-matched analysis, 22% received adjuvant chemotherapy while 78% did not.

Compared to patients who did not receive chemotherapy, chemotherapy recipients were:

  • Younger at a mean age 74 years versus 78 years (P<0.001).
  • More likely to have higher rates of grade 3 disease: 33.1% versus 24.3% (P=0.002).
  • Have larger primary tumors: pT3/T4 tumors at 20.6% versus 14.7% (P=0.005).
  • Have a greater pathologic nodal burden. For example, 21.4% of patients who received chemotherapy had N3 disease versus 6.5% of those who did not get chemotherapy. In contrast, among chemotherapy recipients, 52% had N1 disease versus 75.4% of non-recipients.

For the non-matched cohort overall, median follow-up was 41.4 months (95% CI, 39.7-43.7 months).

Median OS for this cohort was 78.9 months for chemotherapy recipients (95% CI, 68.2 months to not reached) versus 54.9 months (95% CI, 51.3-58.0 months) for non-chemotherapy recipients (P<0.001).

In the propensity-score-matched analysis, median OS in the chemotherapy group was not statistically significant between the 2 groups at 78.9 months (95% CI, 78.9 months to not reached) compared to a median OS in the non-chemotherapy group of 62.7 months (95% CI, 56.2 months to not reached), as investigators pointed out.

Based on multivariate analysis, factors that were significantly associated with a worse OS in the matched cohort included:

  • A Charlson/Deyo score of 3 versus 2 at a HR of 1.94 (95% CI, 1.34-2.79; P<0.001).
  • A higher pathologic T stage (PT4 versus PT1) at a HR of 3.51 (95% CI, 1.86-6.62; P<0.001).
  • A higher pathologic N stage (PN3 versus PN1) at a HR of 1.71 (95% CI, 1.09-2.69; P=0.04).

Conversely, factors associated with improved OS in the matched cohort included:

  • Receipt of endocrine therapy at a HR of 0.47 (95% CI, 0.31-0.72; P<0.001).
  • Receipt of radiation therapy at a HR of 0.61 (95% CI, 0.43-0.87; P=0.006).

As the authors pointed out, the National Comprehensive Cancer Network guidelines recommend that treatment decisions factor in consideration of comorbidities when managing patients with breast cancer who are 70 years of age or older.

Notably, however, in this study, “all patients…underwent breast and axillary surgery despite multiple comorbidities,” the authors noted.

On the other hand, only a subset of these patients received adjuvant chemotherapy—”suggesting that other nonstandardized factors were used in clinical decision-making,” as investigators suggested.

In an editorial comment on the study, Laura Biganzoli, MD, Hospital of Prato, Prato, Italy, and colleagues concurred with the study’s authors that comorbidities can substantially influence decision making in elderly patients with breast cancer as they call into question competing risks of death, reduced functional reserve and a higher risk of toxic effects from adjuvant treatment.

“Chronologic age alone does not fully capture the complexity of elderly patients with cancer,” Biganzoli and colleagues emphasized.

“[And i]n this group of patients, treatment considerations should be individualized based not only on prognostic tumor-related factors but also on the global health status of patients, which is crucial to determine life expectancy and treatment tolerance,” they added.

In fact, despite the availability of online tools (ePrognosis) to help clinicians estimate life expectancy in older patients, the editorialists pointed out that a comprehensive geriatric assessment (CGA) is key to evaluating a patient’s vulnerabilities as it includes an evaluation of domains that can have a substantial impact on the global health of elderly adults.

“These domains include not only comorbidities but also functional status, cognition, nutrition, polypharmacy, social support, psychological issues and spiritual aspects,” the editorialists observed.

“[And] the lack of geriatric parameters in the [current] analysis…represents an important limitation of the study,” they pointed out.

In fact, a CGA is now recommended by the American Society of Clinical Oncology for older patients with cancer receiving chemotherapy and CPA should now be regarded as a standard of care, as Biganzoli and colleagues emphasized.

Limitations of the study include the fact that patients judged not fit for chemotherapy may have received suboptimal treatment with endocrine therapy, further widening the survival gap between those who received chemotherapy and those who did not.

The authors themselves also acknowledged that patients selected to undergo surgery and chemotherapy were more likely to have received both radiation and endocrine therapy, resulting in a potential treatment bias.

“[T]hese limitations may have skewed the population to a healthier cohort who could tolerate treatment associated with improved survival outcomes,” as the authors suggested.

  1. Adjuvant chemotherapy extended median overall survival in elderly patients with estrogen receptor-positive, node-positive breast cancer despite the presence of multiple comorbidities.

  2. Patients who received adjuvant therapies were likely carefully selected as being the most likely to derive benefit from additional therapies despite multiple comorbidities.

Pam Harrison, Contributing Writer, BreakingMED™

Tamirisa had no conflicts of interest to declare.

Biganzoli reported receiving personal fees and/or grants from AstraZeneca, Lilly, Pierre Fabre, Celgene, Daiichi-Sankyo, Eisai, Genomic Health, Novartis, Ipsen, Pfizer and Roche.

Cat ID: 22

Topic ID: 78,22,730,22,691,192