Treatment Modalities and Survival in Older Adults With Metastatic Colorectal Cancer in Real Life

Amandine Gouverneur, PharmD, PhD; Julien Bezin, PharmD, PhD; Jérémy Jové, MSc; Pauline Bosco-Lévy, MD, MSc; Annie Fourrier-Réglat, PharmD, PhD; Pernelle Noize, PharmD, PhD

Disclosures

J Am Geriatr Soc. 2019;67(5):913-919. 

In This Article

Abstract and Introduction

Abstract

Objectives: Metastatic colorectal cancer (mCRC) is increasingly treated with targeted therapies, but little is known about real-life mCRC treatment in older adults. The aims were to describe the real-life first-line treatment modalities in older adult mCRC patients, to identify factors associated with treatment modalities, and to evaluate survival with regard to treatment modalities.

Patients and Methods: A cohort of mCRC patients aged 65 years and older at diagnosis was identified between 2009 and 2013 using French national healthcare insurance system claims data. Treatment modalities were: treatment with one or more anticancer medication vs best supportive care and, among treated patients, treatment with targeted therapy vs conventional chemotherapy alone. Multivariate logistic regression was used to identify factors associated with treatment by anticancer medication and by targeted therapy. Cox proportional hazards models were used to assess the independent effect of treatment modalities on overall survival while adjusting for baseline covariates identified with logistic regression.

Results: A total of 503 patients were included with a median age of 78 years (54% were men). Of these, 299 (59%) were treated with anticancer medications. Among treated patients, 131 (44%) received targeted therapy. In multivariate analysis, age 75 years or older, renal failure, malnutrition, and five or more concomitant medications were associated with a lower likelihood of treatment with anticancer medications. Among treated patients, age 75 years or older, history of cancer, lymph node metastases, and a single metastatic site were associated with a lower likelihood of treatment with targeted therapy. Multivariate Cox proportional hazards models found that treatment with any anticancer medication tended to be associated with a lower risk of death; treatment with targeted therapy was not significantly associated.

Conclusion: A more appropriate prescription of anticancer medications in the older adult will require the definition of more explicit criteria to avoid undertreatment. The real benefit of targeted therapies vs conventional chemotherapy alone needs to be confirmed in this population. J Am Geriatr Soc 67:913–919, 2019.

Introduction

Colorectal cancer (CRC) is one of the most common cancers worldwide. It is more frequent among older adults. Nearly 60% of incident cases are diagnosed in patients 65 years and older.[1] At diagnosis, 20% of patients have at least one metastatic site, and approximately 40% will at one point have metastatic colorectal cancer (mCRC).[2,3]

With the introduction of newer anticancer medications, in particular targeted therapies in 2005, and the enhancement of surgery, the survival of patients with mCRC has improved from approximately 12 months with 5-fluorouracil alone to nearly 30 months with treatment combining conventional chemotherapy and targeted therapy.[4,5] Three targeted therapies are currently recommended in combination with chemotherapy in first-line treatment: bevacizumab, which is an antibody targeting vascular endothelial growth factor, and cetuximab and panitumumab, which are both antibodies targeting epidermal growth factor receptor.[6,7]

According to a recent systematic review, clinical trials of targeted therapies in mCRC suffer from an underrepresentation of older adult or frail patients.[8] These studies provide information on healthy subjects fit to undergo treatment with anticancer medications. In routine clinical practice, observational studies showed that targeted therapies are prescribed to patients who would be excluded from clinical trials because of advanced age or other frailty parameters (eg, comorbidities, physical incapacity, etc). When treated by targeted therapies, older adults have similar survival outcomes to those of younger patients without major safety issues.[9,10] Conversely, an older age still seems to be a barrier to offering treatment with anticancer medications and especially targeted therapies.[11,12] In the absence of clear recommendations for older patients, treatment choice is often difficult owing to specific characteristics that need to be taken into account, such as comorbidities, dependency, biological abnormalities, and social environment.

Because treatment practices may be highly variable in older adult mCRC patients, the aims of the CALBUCO study were (1) to describe the current real-life first-line treatment modalities in older adult mCRC patients, standard treatment including a targeted therapy, conventional chemotherapy alone, and best supportive care (BSC); (2) to identify factors associated with first-line treatment modalities; and (3) to evaluate survival with regard to treatment modalities.

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