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When worlds collide: Chemotherapy near the end of life
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“It’s just common sense. Everybody knows, you have to keep your worlds apart.”
— George Costanza, Seinfeld
Oncology is at an important crossroads, with two major shifts transforming care for patients with incurable cancers simultaneously coming of age.
One of these shifts is the extraordinary proliferation of new cancer-targeted interventions, including biologics, targeted agents and immuno-oncology drugs. In 2014, nearly a fourth of the new drugs approved by the FDA were for the treatment of cancer or cancer-related conditions. These approvals included groundbreaking shifts in how metastatic ovarian, lung and melanoma cancers are managed. For example, agents that affect the programmed death (PD) pathway (eg, pembrolizumab [Keytruda, Merck], nivolumab [Opdivo, Bristol-Myers Squibb]) have transformed metastatic melanoma from a disease conferring almost-immediate hospice eligibility to one with OS measured in several months. With such approvals, suddenly and rapidly a bevy of treatment choices using novel pathways and approaches are available for conditions previously with inferior outcomes or without drug options.
The other paradigm shift involves how oncologists support, communicate, and make decisions with patients — oncology today explicitly strives to be kinder, gentler and more supportive than ever before. Strategies incorporating palliative care and hospice earlier and more often, alongside integration of shared-decision approaches, are part of this transformation. Thoughtful conversations regarding meeting patient goals, easing transitions throughout the disease trajectory and supporting quality of life (as defined by patients) are increasingly woven into the fabric of usual oncology care. Quality of life, financial toxicity and psychosocial needs are now regarded with an air of relevance approaching that of more recognized outcomes like PFS and OS. The focus is not always on living longer, no matter what the cost. The role of the oncologist is being reimagined — to go beyond “the giver of chemotherapy” — as a compassionate clinician focused on cancer who uses chemotherapy as but one tool to help his or her patients.
But how do we reconcile both shifts — the advent of better and newer cancer drugs and a greater focus on quality of life — when they seem to advocate for diametrically opposite outcomes? Is an “and/with” mindset, instead of an “either/or” approach possible? Or, are we served better by keeping the two seemingly contradictory worlds apart, pitting the influence of each side against each other, allowing for the best perspective to win?
Prigerson and colleagues reported the results of a study evaluating quality of life near death of patients who received chemotherapy in the last 6 months of life. The researchers found that quality of life near death as reported by caregivers was worse for patients with good performance status (ECOG 1) who received chemotherapy vs. those who had not. They did not observe such differences in patients with poor performance status. This was among the first studies to use multisite data to critically evaluate the utility of chemotherapy given when clinicians estimated a prognosis short enough for hospice eligibility.
This study is important for several reasons. First, the authors should be commended for conducting and reporting such a study that builds the foundation of an evidence base that is largely nonexistent. Assumptions regarding the utility of chemotherapy to support quality of life are largely asserted, with minimal evidence that support such conclusions with the analytic finesse and rigor that the authors used. Second, the conclusions draw from a large dataset across several sites, allowing for some generalizability to be drawn from the findings. Third, the authors use a validated approach to measure quality of life near death by incorporating the report of caregivers during the time near end of life when patient report is difficult or fraught with confounders. Most importantly, the authors highlight the necessary role of thoughtful, regular and honest conversations between clinicians, patients and caregivers regarding the likely, unexpected and best-case/worst-case outcomes that can result from all treatment approaches on the table. Like everything else in oncology, the authors remind us there are few straightforward answers — we all benefit from complete information and authentic collaboration.
What conclusions should we be careful to make after reading the study? First, caution should be taken before making general assumptions about the utility of all cancer-targeted agents for patients with limited life expectancy. The study was conducted between 2002 and 2008, largely before the growth of new therapeutic approaches (eg, immuno-oncology agents with preferable side-effect profiles compared with standard chemotherapy), regular use of modern supportive care interventions (eg, neurokinin inhibitors for highly emetogenic chemotherapy) and the regular incorporation of palliative care deployed in parallel to oncology care. For example, palliative care services across the U.S. have grown 148% in the last decade. Remarkably more cancer patients can access palliative care during usual oncology care now compared to 2002. Second, the population analyzed within the study was very specific, including patients who had an estimated 6 months expected survival and had completed at least one previous chemotherapy regimen. As Blanke and Fromme articulated in an accompanying editorial, oncologists are notorious for overestimating patient survival, meaning that patients included in the study were further along the disease trajectory than the estimated prognosis might indicate. Third, chemotherapy undoubtedly plays a major role in assisting patients with incurable disease. For patients newly diagnosed with metastatic colon cancer who do not receive any cancer-directed treatment, prognosis is measured in months. But, with the advent of modern chemotherapy regimens, survival measured over 3 years is more likely than ever before. Like with treating patients and cancer types, a “one-size-fits-all” approach to decisions regarding chemotherapy in incurable settings makes little sense.
The study from Prigerson and colleagues highlights the importance of letting the two worlds — one advocating for cancer-directed treatment and the other promoting quality of life — to naturally coalesce with one another. For those Seinfeld buffs who understand this reference, we know that worlds colliding can be difficult — George certainly did not handle it well. We must constantly remind ourselves that chemotherapy is not the only tool in our toolbox, and how individual patients make decisions that affect life and death, quality of life and misery is as unique to that patient as his own genetic fingerprint. We are becoming more adept at matching the genetic fingerprints of tumors to the appropriate targeted agent. Simultaneously, and no less importantly, we must become more proficient at aligning patient wishes with the right intervention when time is short, be that chemotherapy or something else.
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- Arif H. Kamal, MD, an oncologist and palliative medicine physician, is director of quality and outcomes at Duke Cancer Institute. He can be reached at arif.kamal@duke.edu.
Disclosure: Kamal reports no relevant financial disclosures.