KERAMIDA IS WORKING-ROLE OF PALLIATION IN LUNG CANCER TREATMENT

August 19, 2010 — Introducing palliative care at diagnosis, in parallel with standard oncologic care, led to a significant improvement in survival in patients with metastatic nonsmall-cell lung cancer (NSCLC).

The finding comes from a study of 151 patients conducted by a team at the Massachusetts General Hospital in Boston, headed by Jennifer Temel, MD. The results appear in the August 19 issue of the New England Journal of Medicine.

The study was praised as being paradigm-shifting in an accompanying editorial and as "precedent-setting" by an expert in the field of palliative medicine.

Patients who received simultaneous palliative care and standard oncologic care had a significantly better quality of life and significantly lower rates of depression than those who received only standard care.

They also lived longer — median survival for patients in the simultaneous-care group was 11.6 months and in the standard-care group was 8.9 months (P = .02). This survival benefit of 2.7 months is similar to that achieved with standard chemotherapy regimens.

"We were thrilled with the results," Dr. Temel told Medscape Medical News.

"Improving quality of life and mood in patients with metastatic NSCLC is a formidable challenge, given the progressive nature of the disease," she noted.

This patient population usually shows a deterioration in quality of life over time, and this was seen in the control group of the study, but the quality of life actually improved over time for patients receiving early palliative care, Dr. Temel pointed out.

"There is a great deal of data in the literature supporting the premise that patients with a better quality of life live longer than patients with [a worse] quality of life or depression, so we believe that the improvements [seen in this study] certainly contributed to the survival benefit," she said.

"Perhaps unsurprisingly, reducing patients' misery may help them to live longer," according to an accompanying editorial by Amy Kelley, MD, MSHS, and Diane Meier, MD, from the Mount Sinai School of Medicine in New York City.

Although the survival benefit needs to be replicated, this study challenges prevailing notions about palliative care being something that is offered only after standard care has failed, they write.

Shifts a Long-Held Paradigm

"Physicians tend to perceive palliative care as the alternative to life-prolonging or curative care — what we do when there is nothing more that we can do — rather than as a simultaneously delivered adjunct to disease-focused treatment," the editorialists write.

As a result of these perceptions, the use of palliative services remains low, they add.

However, this new study shows that introducing palliative care at the time of diagnosis, at the same time as other appropriate and beneficial medical therapies, is both "appropriate and potentially beneficial," they note.

"This study . . . shifts a long-held paradigm that has limited access to palliative care to patients who are predictably and clearly dying," the editorialists conclude.

Sets New Precedents

This study is "precedent-setting for all of us in the palliative-care field," said Charles von Gunten, MD, PhD, who is provost of the Institute for Palliative Medicine at the San Diego Hospice in California, in a statement issued after the results appeared.

It demonstrates that palliative care "should not be considered a last resort or giving up," he said, adding that it "should be offered as early as possible as part of standard treatment."

Physicians remain reluctant to recommend palliative care, and patients are reluctant to accept it, Dr. von Gunten noted. "They often feel as if it means they are abandoning hope, but this is not at all the case," he emphasized.

"Frequently, the benefits of palliative care allow someone to live much longer than expected, as this groundbreaking study shows. More important, though, is the ability of palliative medicine to greatly improve the quality of life, to make the most of whatever hours, days, weeks, months, or more are left, expanding an individual's time with family and friends and the things they love most in life."

There is also praise for the study from Leonard Lichtenfeld, MD, MACP, deputy chief medical officer for the national office of the American Cancer Society, who highlights the survival benefit in a recent blog.

"If that degree of improvement in life expectancy was seen in a clinical trial looking at survival after treatment with a new chemotherapy drug, there would be applause all over the place. Instead, I fear that many physicians will just yawn and say something to the effect of "Here they go again with that pain stuff," he writes.

Yet all physicians should take note of these results, he says. "Maybe it's time to realize that with all of our powerful medicines and other treatments we still have one medicine that we don't utilize often enough, and that is genuine caring and support for someone in distress."

Happier Patients?

The study involved 151 patients with pathologically confirmed metastatic NSCLC. All but 1 patient received chemotherapy (with platinum-based combinations, and in some cases an oral EGFR tyrosine kinase inhibitor), and about one third received radiotherapy.

Although the study was randomized and controlled, it could not be blinded because both patients and clinicians were aware of the palliative-care assignment.

Patients who received simultaneous care showed significant improvements on several measures, the researchers report.

Quality of life was significantly improved on all 3 measures that were used. After 12 weeks, scores on the Trial Outcome Index had increased by 2 points in the simultaneous-care group, but had dropped by 2 points in the standard-care group (P = .04).

This improvement in quality of life is similar to that observed in previous studies of patients who have a response to cisplatin-based chemotherapy, Dr. Temel and colleagues explain.

Depression rates in the simultaneous-care group were nearly half those seen in the standard-care group (38% vs 16%; P = .01), despite the fact that antidepressant use was similar in both groups.

Commenting on these findings, Dr. Temel said that "we very much hoped to see improvements in quality of life and rates of depression, but we were happily surprised by the magnitude of the impact in both measures."

Survival was also significantly improved, despite the fact that the group receiving palliative care had less aggressive end-of-life care (33% vs 53%; P = .05).

Dr. Temel and colleagues hypothesize that it is the improvements in quality of life and depression that account for the observed survival benefit. But they also suggest that the earlier referral to a hospice program might result in care that provides better management of symptoms, leading to stabilization of the patients' condition and improved survival. Both of these hypotheses require further study, they note.

The editorialists add that the improvement in survival seen might result from the effective management of depression, the improved management of symptoms, or a reduction in the need for hospitalization. "The study was not designed to address these important questions," they point out.

Specific components of the palliative care intervention remain unspecified and, hence, might not be easily reproducible in other practice settings, the editorialists add. "For example, the salutatory effect of additional time with and attention from healthcare providers and physicians, as opposed to a specific benefit derived from palliative care itself, was not assessed and is a limitation of the study," they note.

Nevertheless, this study represents an "important step in confirming the beneficial outcomes of a simultaneous-care model that provides both palliative care and disease-specific therapies beginning at the time of diagnosis," Drs. Kelley and Meier write in their editorial.

"We now have both the means and the knowledge to make palliative care an essential and routine component of evidence-based, high-quality care for the management of serious illness," they conclude.

The study was supported by an American Society of Clinical Oncology Career Development Award and by philanthropic gifts from cancer funds. Dr. Temel and coauthor Thomas Lynch, MD, report receiving payment for continuing medical education from InforMEDical. Dr. Lynch also reports serving on the board of Infinity Pharmaceuticals; receiving consulting fees from Roche, Boehringer Ingelheim, Merck, AstraZeneca, Bristol-Myers Squibb, and Sanofi-Aventis; and receiving royalties from Partners HealthCare. The editorialists have disclosed no relevant financial relationships.

N Engl J Med. 2010;363;733-742, 781-782.