Novel Agents in the
Treatment of Lung Cancer
New Approaches to First-Line Therapies
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Integration of Early Palliative Care in the Treatment of Metastatic NSCLC
Patients with metastatic NSCLC experience a high symptom burden beginning at the time of diagnosis, which persists throughout the course of disease. These patients suffer from not only physical symptoms such as fatigue and dyspnea, but also emotional distress such as anxiety and depression.75-77 Respiratory symptoms such as dyspnea and cough are particularly troubling and distressing in this patient population.78 There are also high rates of distress and anxiety in the family members of patients with advanced disease.79
Not only do patients with metastatic NSCLC face the challenging symptoms associated with the disease and the therapies used to treat it, but they also confront difficult decisions about goals of care. While chemotherapy prolongs survival in this disease, for most patients the impact on life expectancy is quite small. The progression-free survival for first-line therapy, even with modern 3-drug regimens, is measured only in months, and responses to second-line therapy and beyond are often rare.1,7 In addition, there are not clear data for chemotherapy beyond third-line therapy, and there can certainly be a quality-of-life (QoL) tradeoff with prolonged therapy. Discussions about the potential risks and benefits of chemotherapy and deciding when to stop chemotherapy and pursue supportive care alone are quite challenging for oncology providers.
Data suggest that many patients with metastatic NSCLC hold fairly inaccurate views of their health status and goals of therapy. A study of 150 patients with newly diagnosed metastatic disease found that less than 15% of patients viewed themselves as terminally ill and approximately one third believed their cancer to be curable.80 While patients accurately reported that the goals of therapy were to help them feel better and live longer, two thirds also viewed getting rid of all cancer as a goal. Data suggest accurate prognostic understanding does not negatively impact hopefulness or mood and may lead to more appropriate and less costly end-of-life care.81,82 Despite this, we know that physicians often portray an overly optimistic prognosis to their patients.83 This has important societal implications as cancer care is becoming more aggressive, and therefore costly, over time, and conversations about end-of-life care may result in significant cost savings.84,85 Therefore, interventions to improve patient-clinician communication regarding prognosis and goals of care are clearly warranted.
In light of the prevalence of symptoms and the complex decision-making faced by patients with metastatic NSCLC, they may benefit from greater supportive care during the course of their disease. Palliative care providers are specially trained both in symptom management and in providing psychosocial support for patients and families. There are data to suggest that patients with later-stage metastatic cancers do benefit from outpatient palliative care consultations.86 A recent study of 150 patients with a variety of tumor types who were referred to an outpatient palliative care clinic for assistance with symptom management demonstrated improvements in both symptoms and satisfaction with care.87
The above data suggest that palliative care services can benefit patients who are referred for consultation for uncontrolled symptoms or assistance with end-of-life care planning. However, this model of care relies on the primary oncology providers actually referring patients for a palliative care consultation. This is problematic because oncology clinicians do not always realize when patients are experiencing troubling symptoms or when patients and families are facing significant distress. In addition, referring patients and families for palliative care consultation only once they are outwardly struggling with their illness may be missing an important window to improve their QoL earlier in the course of disease. When family members of deceased cancer patients are asked about the timing of palliative care referrals, the majority report that the timing was too late.88
Based on these concerns, many consensus guidelines are recommending earlier involvement and integration of cancer and palliative care to better support our patients facing life- threatening illnesses.89 However, this new paradigm of care has not yet been widely adopted. It clearly demonstrated that palliative and oncology care should be integrated earlier in the course of disease in patients with incurable cancers. Recent data do suggest that a more integrated model of cancer and palliative care is feasible.76 This study included ambulatory NSCLC patients with newly diagnosed incurable disease who were scheduled to meet with both oncology and palliative care providers throughout the course of their disease. More than 90% of the study participants were compliant with their scheduled palliative care visits, suggesting that the integrated model of care is reasonable in this patient population.
To definitively demonstrate the benefits of integrated palliative and oncology care would require a randomized study. To date, most studies of palliative care interventions have been single-arm, nonrandomized studies. One study that demonstrated improvements in several common symptoms in patients with a variety of life-threatening illnesses, including cancer, did include a control arm, but patients were not randomized.90 Another study randomized cancer patients with a limited life expectancy to conventional care or cooperative care with a palliative care unit, but failed to show an improvement in QoL.91
More recently, a randomized, controlled study of a nurse-led telephone intervention with a focus on palliative care did show improvements in patient-reported outcomes.92 This study included newly diagnosed patients with lung, colon, and breast cancer, and randomized participants to usual care or a structured program including educational and problem-solving sessions and at least monthly follow up, all via telephone. Patients randomized to the nursing intervention had only moderate, but statistically significant, improvements in a palliative care QoL measure and mood. While this is certainly evidence that patient-focused supportive programs may have an impact on mood and QoL outcomes, the intervention is this study was not a traditional palliative care model of care.
We have recently completed accrual to a large, randomized, controlled trial of standard oncology care versus integrated palliative and oncology care. The study enrolled patients within 8 weeks of diagnosis of incurable NSCLC who were receiving their cancer care at Massachusetts General Hospital. The study is powered to detect a difference in quality of life at 12 weeks between the 2 study arms. Additional study aims include family caregiver satisfaction, illness under standing, and aggressiveness of care at the end-of-life. We hope to have data on the primary and secondary outcomes of this study by ASCO 2010.
Conclusion
Providing predominantly anticancer therapy to patients with metastatic NSCLC may not be sufficient to provide them and their loved ones with the support and assistance they need. Preliminary data suggest that a more multidisciplinary approach with integrated oncology and palliative care can impact patients’ QoL and mood. While this needs to be confirmed with large, randomized, controlled trials, other important outcomes such aggressiveness of care and hospice utilization should also be examined. Chemotherapy, emergency room visits, and hospital and intensive care unit admissions near the end of life, along with short length of stay in hospice for patients with incurable malignancies, have a major impact on the health care economy. In-patient palliative care consultations have been demonstrated to decrease in-hospital costs, and a similar result with palliative care in the ambulatory care setting could have a significant impact on health care costs.93
Discussion
Dr. Hanna: In general, we are as a profession undereducated on supportive care, palliative care, and understanding what hospice does for patients. It seems like hospice is a frightening thing to offer patients, and unless you really explain what it is and what it isn't, patients often push back on the thought of going on hospice. I think physician attitudes make a big difference. I try to speak to my patients about the mental pain they have, but I think physicians underestimate how much anxiety patients are experiencing. I encourage patients to make it a major focus of their care. Instead of saying go to a psychiatrist or giving them some antidepressant, I really focus on why that’s such an important aspect of their quality of life. I've asked my staff to educate me on this. I wish we could formalize training in palliative care more.
Dr. Temel: When we first started doing this work, the oncologists said, "we don’t need this, we are already doing this." But once you've spent an hour explaining how the drugs work, it's hard to find the time to address psychosocial distress issues and fears. It helps to have a third party who is not the one "giving the drugs" to address other issues of care. Patients often want to be, and have their physician be, positive about how well the chemotherapy or other drugs will work. But there can be a different honesty, if you're not the one ordering the chemotherapy.