Monday, January 2, 2012

The Alignment of HPM and Oncology: Palliative Care Influence on Chemotherapy Use in Metastatic NSCLC

We continue to learn more from the landmark randomized controlled trial conducted by Temel et al from NEJM which demonstrated that outpatient palliative care consultation for patients with newly diagnosed Stage IV lung cancer improves quality of life and may also improve survival by a few months.

Although the survival advantage was a secondary outcome in the original NEJM study, it remains the headliner outcome.  For many who were stuck in an old paradigm of considering palliative medicine as the option of last resort after all other therapies have failed, there was a strong association (mentally, not scientifically) with an idea that hospice and palliative care for patients with cancer meant “letting go of the rope” (i.e. stopping chemotherapy) and that when the transition was made, the patient would go into a free fall towards their death as a result of “letting go.”  Although some lesser quality studies had already suggested that hospice and related interventions might not shorten life and may even prolong it, it was still pleasantly surprising (and for some, inexplicable) when this randomized controlled trial demonstrated a survival advantage for patients seen by a palliative care team. 

"Aikido" from
Wikimedia Commons

As with any result in a clinical trial, it helps to have a plausible mechanism of action to explain the result.  Since this was a “bundled” intervention, it may be difficult to tease out the exact reason why palliative care patients lived longer. Many explanations have been proposed.  Chemotherapy definitely has a role for life-prolongation but has side effects.  Could it be that palliative care helps patients with those side effects, allowing them to receive more of it?  Conversely, could palliative care “protect” patients from toxic chemotherapy near the end of life when chemo may do more harm than good?  Alternatively, is there something intrinsic to palliative care which prolongs life irrespective of chemotherapy?

Last week, the Journal of Clinical Oncology released a secondary analysis of the data from the initial NEJM study data which further elucidates the differences in chemotherapy utilization between the palliative care and standard groups to try to help answer some of these questions.  The authors also reexamined healthcare utilization at the end of life.  Here are some bottom lines.  The palliative care wing did not appear to receive more chemotherapy.  The two groups did not differ with respect to initial anti-cancer therapy (and only one patient…in the standard care wing, incidentally.... didn’t receive anti-cancer therapy at the onset of the trial).  They examined the use of multiple lines of chemotherapy (first, second, third, fourth, and beyond).  Once again, there was no difference between the groups nor was there any difference in how much time it took for the groups to arrive at the next line of chemo. 

How did the two groups differ, then?
  • Days between last IV chemotherapy dose until death (Palliative care group median 64 days vs. Standard Care median 40 days, p=.02).  For oral chemo, the results were 27 days and 17 days respectively but this was not statistically significant.
  • Chemotherapy use in last 60 days of life (Palliative care group 52.5% vs. 70% in the Standard Care group, p=0.05).  A trend towards less chemo use in last 30 and last 14 days of life as well but not statistically significant.
  • Hospice utilization:  While there was no difference between groups with respect to the percentage of patients utilizing hospice, the palliative care group received hospice services longer (median of 24 days vs. 9.5 days in the standard care group).  In the palliative care group, 60% of patients received hospice >7 days before death compared to 33% in the standard care group.  (More on this below.)
When examining location of death, a slightly greater proportion of the palliative care group died at home compared to an inpatient hospice, hospital, or nursing facility, but this was not statistically significant.

It should be noted that the study was not powered to look at many of these outcomes such as chemo use in the last month and 14 days of life as well as location of death.  For instance, with a larger sample size, it’s possible that the increased incidence of home death in the palliative care group might have risen to statistical significance.  However, the lack of statistically significant difference here is not surprising.  While hospital based palliative care can prepare patients/families for the challenges which may come near the end of life, the provision of adequate care within the home to ensure a peaceful death involves many factors which may be outside the purview of the intervention described in the study (e.g. the development of unpredictable symptoms which are difficult to manage at home, capability of caregivers, capacity of the home hospice, etc). 

The study still doesn’t definitively answer the survival mechanism of action question, it only suggests that aggressive chemo at the end of life is not the reason.  The median survival advantage in the original study was about 2.7 months.  In this study, patients receiving the palliative care intervention were free from IV chemo 24 days longer at the end of life and received 14 days more of hospice which doesn’t add up to 2.7 months.  Avoidance of toxic chemo near the end of life and provision of supportive hospice likely play a role, but in the shadows, there appears to be a survival benefit which is unrelated to chemo avoidance or hospice. Improved symptom control and psychological well-being, perhaps?  In Temel et al, the primary outcome was improved QOL 12 weeks after initiation of the intervention.

While we are talking about the study being underpowered, I do have to point out that there was a statistically insignificant trend towards the palliative care group having a longer time from first to second line and from second to third line chemo (0.8 months longer in each case).  This result came about only when participants were censored at time of analysis--when the numbers were crunched censoring participants at either date of death or date of analysis, there was no difference between groups in time to next line of chemo.  I'm not sure which method is better for detecting a difference between groups, but this does suggest that with greater power, the study might have detected a statistically significant difference.  In other words, we still can't rule out the possibility that palliative care helped patients receive more chemo early on in the course of their cancer therapy.

It was never my hypothesis that palliative care helped patients receive more chemo, thus resulting in the survival advantage.  I've always thought that the benefits of excellent symptom/psychosocial support and avoidance of chemo near the end of life were more plausible explanations.  Don’t confuse this with a bias against chemotherapy for patients with advanced lung cancer.  I fully embrace the role for chemotherapy in advanced lung cancer and the palliative care practitioners in this study were obviously not chemotherapy obstructionists.  I am familiar enough with oncology clinical trials (without being an oncologist) to know they lend more guidance to oncologists regarding when to start the agents and less guidance regarding when to stop. While sometimes the decision to stop is clear cut (patient has catastrophic complication or documented progression of disease on imaging with performance status slipping to ECOG 3), there are other times when the decision is more arbitrary.

For example, consider a patient in the middle of third line chemo who is experiencing more fatigue whose ECOG slips from 1 to 2 where everyone is suspecting progression but it may be just as easy to continue with the status quo until the next scan or until a complication comes up.  At this point, many patients may be thinking that pushing forward with chemo isn't worth it to them, but what's next?  That question is often wrought with fear.  Palliative care might help “tip the scales” towards discontinuation in this circumstance a couple of ways.  Through advance care planning discussions, "what next" becomes clearer: The role of hospice may be better understood and end of life fears already addressed.  Even if hospice isn’t initiated immediately, palliative care is already part of the status quo, perhaps enabling either the oncologist or the patient to be more proactive with saying “hey, this (chemo) doesn’t seem like it’s working” with less of a feeling that they are “giving up.”

One of the most frequently noted caveats to this study is the fact that it's a single institution. Other institutions vary with respect to patient population, oncology practice, and palliative care team practice.   The palliative care intervention brought the median hospice length of stay just above the national median (21.1 days in 2009) and 60% of the palliative care patients received hospice >7 days which is below the national rate of 65%. (Source: NHPCO Facts and Figures).   It's worth remembering that the palliative care intervention followed guidelines from the National Consensus Project for Quality Palliative Care. Adherence to those guidelines at other institutions should also mean that patients will see many of the same benefits even if the results of Temel et al and the present study couldn't be exactly replicated.
It’s notable that the American Society of Clinical Oncology (ASCO) is looking carefully at the quality of end of life care within oncology programs (quote from present study):
“With accumulating evidence for the benefits of earlier referral to hospice for patients with terminal cancer, leaders in oncology have established guidelines for quality end-of-life care. The American Society of Clinical Oncology Quality Oncology Practice Initiative has delineated several key metrics for determining high-quality treatment near death, such as no chemotherapy within the last 2 weeks of life, referral to hospice, and enrollment in hospice care more than 1 week before death.  Palliative care clinicians, who are accustomed to practicing within a multidisciplinary team, are ideally suited to support oncology providers, patients, and families in discussing and planning for such treatment at the end of life. To date, to our knowledge, no studies have shown the utility of these services for altering the quality of end-of-life care.”
The QOPI measures are worth reviewing.  As palliative care programs track metrics and achieve TJC certification, it's only natural that we should work with our oncology colleagues to help with the end of life QOPI metrics as well.  The results of this study indicate that our work helps oncologists with those measures. 

Lastly, a friendly editorial which accompanies the study is also worth a read. 

Pallimed | Blogger Template adapted from Mash2 by Bloggermint