Supportive care: bringing better cancer treatment

Clinique de Genolier

Supportive care: bringing
better cancer treatment

by M. Aapro, Switzerland

Guideline-directed treatment, including that for supportive care, is cost reducing and improves patient outcomes, but recent developments increasing therapeutic modalities have introduced new types of toxicities; thus, new treatment algorithms will be required. We have already seen a positive impact on patient survival owing to granulocyte colony-stimulating factors, bisphosphonates, and possibly denosumab, to name a few examples. Furthermore, early palliative care has been shown to impact mortality due to cancer in 3 randomized studies. Despite the European Society for Medical Oncology’s (ESMO) position taken in 2003, calling for the development of optimal supportive and palliative care, patients unfortunately continue to be seen late in the course of illness. Nowadays, as delivering affordable medical care is a major challenge even for countries with a relative wealth of resources, one would imagine this would be more acutely felt in countries that are more limited in that regard. To best allocate their resources, such countries could adapt existing recommendations—such as those covering physical symptom management, pain management, monitoring and documentation, psychosocial and spiritual aspects of care, health professional education, as well as patient, family, and caregiver education—to priorities suggested by a consensus panel, similar to that suggested by the Breast Health Global Initiative.

Medicographia. 2015;37:330-333 (see French abstract on page 333)

There is no doubt that we have made progress in controlling many symptoms related to classic cancer treatments, and consensus or guideline publications provide information for the clinician to improve patient care,1-4 both in younger and older patients.5 This is of course true only as long as guidelines are applied (Figure 1).6 When properly used, guideline-directed treatment is also cost reducing.7

Nevertheless, new challenges are emerging for supportive care, as discussed recently in a commentary in the journal of the Multinational Association for Supportive Care in Cancer (MASCC).8 As stated by the authors, these challenges are exacerbated by the expected increase in the number and type of targeted therapies that will enter the oncologist’s arsenal based on new research and approvals. New treatment algorithms will be required, and there is a need to explore the management of these toxicities using novel approaches, including pharmacogenomics and genetic risk prediction in order to personalize management strategies.

Figure 1
Figure 1. Following MASCC/ESMO antiemetic guidelines improves
prevention of chemotherapy-induced nausea and vomiting.

The control rate represents the percentage of patients with complete response
(no nausea or vomiting and no rescue medication) in the overall (0-120 hours),
acute (0-24 hours), and delayed phases (24-120 hours). P<0.05 for all differences. Abbreviations: ESMO, European Society for Medical Oncology; MASCC, Multinational
Association for Supportive Care in Cancer.
Based on data from reference 6: Aapro et al. Ann Oncol. 2012;23:1986-1992.

Supportive care: is there a survival benefit?

Those who believe only in survival data will ask if this type of research is justified, looking at the potential impact of supportive care on patient survival. The answer is that a positive impact on survival is very likely in some cases, as shown in analyses about the proper application of granulocyte colony-stimulating factors.9,10 Also, it seems that a survival benefit is observed in patients treated with bisphosphonates in several settings, from multiple myeloma11 to postmenopausal patients with early breast cancer,12 and in a hypothesis-generating evaluation of denosumab in non–small cell lung cancer (NSCLC), for example.13 Clearly, one will find it difficult to show a survival impact of antiemetic studies, even if most professionals accept that nausea and vomiting are unacceptable side effects of oncological treatments.

An unforeseen impact of early palliative care

Among busy clinicians, interest for early palliative care was sparked by a study in patients with NSCLC that was published in 2010.14 The authors randomly assigned patients with newly diagnosed metastatic NSCLC to receive either early palliative care integrated with standard oncologic care or standard oncologic care alone. The primary outcome was the change in the quality of life (QOL) at 12 weeks, but the authors observed an unexpected impact on survival. Among the 151 patients who underwent randomization, median survival was longer in patients receiving early palliative care (11.6 months vs 8.9 months; P=0.02). Patients assigned to early palliative care had a better QOL than did patients assigned to standard care (mean score of 98.0 vs 91.5; P=0.03; on the Functional Assessment of Cancer Therapy – Lung scale [FACT-L], in which scores range from 0 to 136, with higher scores indicating better QOL). In addition, fewer patients in the early palliative care group had depressive symptoms, compared with the standard care group (16% vs 38%; P=0.01). A paper published by the same group showed that depression predicted worse survival in patients in that study with newly diagnosed metastatic NSCLC. Although early palliative care was associated with greater improvement in depression at 12 weeks, the data did not support the hypothesis that treatment of depression mediated the observed survival benefit from early palliative care.15

The American Society of Clinical Oncology (ASCO) then put together a group that published a provisional clinical opinion on the topic in 2012.16 This evaluation of the available evidence (7 randomized controlled trials) about the benefits of palliative care in patients with metastatic cancer who are also receiving standard oncologic care concluded that survival benefit from early involvement of palliative care had not yet been fully demonstrated. However, the review panel concluded that palliative care—either combined with standard oncologic care or as the main focus of care—leads to better outcomes in patients and caregivers, and should be considered early in the course of illness for any patient with metastatic cancer and/or high symptom burden.

Other evidence for early palliative care in advanced cancer

Since then, 2 other studies have shown the importance of early access to supportive or palliative care. The first17 was a study conducted at the Princess Margaret Cancer Centre (Toronto, ON, Canada), between Dec 1, 2006, and Feb 28, 2011. A total of 24 medical oncology clinics were cluster randomized (in a 1:1 ratio, using a computer-generated sequence, stratified by clinic size and tumor site [4 lung, 8 gastrointestinal, 4 genitourinary, 6 breast, 2 gynecological]), to consultation and an at least monthly follow-up by a palliative care team (intervention group) or to standard oncologic care (control group). Eligible patients had advanced cancer, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and a clinical survival prognosis of 6-24 months. Several scales, including the Functional Assessment of Chronic Illness Therapy – Spiritual well-being scale (FACIT-Sp), were used at baseline and monthly for 4 months to obtain study measures. The primary outcome was FACIT-Sp change score at 3 months.

In that study, 461 patients completed baseline measures (228 in the intervention group, 233 in the control group); 393 completed at least 1 follow-up assessment. At 3 months, there was a nonsignificant difference in change score for FACIT-Sp between intervention and control groups (3.56 points; 95% confidence interval, –0.27 to 7.40; P=0.07), but differences in all other scales favored the intervention group. The authors concluded that this trial shows promising findings that support early palliative care for patients with advanced cancer.

The second study, which has just been published,18 investigated the effect of early versus delayed palliative care on outcomes, including QOL, symptom impact, mood, 1-year survival, and resource use (days in hospital/intensive care unit, emergency room visits, chemotherapy in last 14 days, and death location). Between October 2010 and March 2013, 207 patients with advanced cancer at a National Cancer Institute (NCI)-designated cancer center, a Veterans Affairs (VA) medical center, and community outreach clinics were randomly assigned to receive an in-person palliative care consultation, structured palliative care telehealth nurse coaching sessions (once per week for 6 sessions), and monthly follow-up either early after enrollment or 3 months later. The overall patient- reported outcomes were not statistically significant after enrollment (QOL, P=0.34; symptom impact, P=0.09; mood, P=0.33) or before death (QOL, P=0.73; symptom impact, P=0.30; mood, P=0.82). However, the Kaplan-Meier 1-year survival rate was 63% in the early group and 48% in the delayed group (difference, 15%; P=0.038).

Does it matter?

Though survival benefit results in supportive care studies are very encouraging to read about, are they necessary? Is it really important to show that quantity of life is influenced by supportive and palliative care interventions? Does anyone dispute the importance of pain control, which perhaps does not influence the quantity of life, but could influence the quality of survival? Is there really room for the never-ending dispute among healthcare professionals about supportive or palliative care?19

Back in 2003, the European Society for Medical Oncology (ESMO) had already taken a position calling for the development of optimal supportive and palliative care.20 However, despite the support given for the development of centers of excellence in this field, a recent survey has shown that palliative care facilities are used late in the course of disease, which is unsatisfactory.21 Data was generated from members of MASCC, ESMO, and the European Association of Palliative Care (EAPC), who completed the surveys online. A total of 62 program leaders completed the survey. Most programs had been in existence for over 5 years and were led by oncology- trained physicians who had an additional specialty. Most programs had consultative services and outpatient clinics with fewer having inpatient beds and institutionally associated hospices. Most programs provided patient continuity. Patients were generally seen late in the course of illness with the average survival of 23 days when seen as inpatients and 40 days when seen as outpatients.

Now what?

Clearly, the guidelines and consensus recommendations cannot be universal. Even countries with excellent resources are facing a crisis related to the costs of medicine.22 If these countries have limitations, what can be said about those with fewer resources? An example of one review addressing this issue is the Breast Health Global Initiative (BHGI), which has convened 3 expert panels to develop resource allocation recommendations for supportive and palliative care programs in low-income and middle-income countries.23 Each panel focused on a specific phase of breast cancer care: during treatment, after treatment with curative intent (survivorship), and after diagnosis with metastatic disease. The panel consensus statements—which cover physical symptom management, pain management, monitoring and documentation, psychosocial and spiritual aspects of care, health professional education, and patient, family, and caregiver education— were published in October 2013.24 Such panels may offer guidelines on how best to implement care recommendations according to available resources.

1. Coleman R, Body JJ, Aapro M, et al; ESMO Guidelines Working Group. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2014; 25(suppl 3):iii124-iii137.
2. Aapro M, Arends J, Bozzetti F, et al. Early recognition of malnutrition and cachexia in the cancer patient: a position paper of a European School of Oncology Task Force. Ann Oncol. 2014;25:1492-1499.
3. Aapro MS, Bohlius J, Cameron DA, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011;47:8-32.
4. Roila F, Herrstedt J, Aapro M, et al; ESMO/MASCC Guidelines Working Group. Guideline update for MASCC and ESMO in the prevention of chemotherapyand radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol. 2010;21(suppl 5):v232-v243.
5. Naeim A, Aapro M, Subbarao R, Balducci L. Supportive care considerations for older adults with cancer. J Clin Oncol. 2014;32:2627-2634.
6. Aapro M, Molassiotis A, Dicato M, et al. The effect of guideline-consistent antiemetic therapy on chemotherapy-induced nausea and vomiting (CINV): the Pan European Emesis Registry (PEER). Ann Oncol. 2012;23:1986-1992.
7. Kosimbei G, Hanson K, English M. Do clinical guidelines reduce clinician dependent costs? Health Res Policy Syst. 2011;9:24-29.
8. Chan A, Lees J, Keefe D. The changing paradigm for supportive care in cancer patients. Support Care Cancer. 2014;22(6):1441-1445.
9. Lyman GH, Reiner M, Morrow PK, Crawford J. The effect of filgrastim or peg filgrastim on survival outcomes of patients with cancer receiving myelosuppressive chemotherapy. Ann Oncol. 2015 Apr 7. Epub ahead of print. pii:mdv174.
10. Lyman GH, Dale DC, Culakova E, et al. The impact of the granulocyte colonystimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials. Ann Oncol. 2013;24:2475-2484.
11. Morgan GJ, Davies FE, Gregory WM, et al; National Cancer Research Institute Haematological Oncology Clinical Studies Group. Effects of induction and maintenance plus long-term bisphosphonates on bone disease in patients with multiple myeloma: the Medical Research Council Myeloma IX Trial. Blood. 2012;119:5374-5383.
12. Coleman R, Gnant M, Morgan G, Clezardin P. Effects of bone-targeted agents on cancer progression and mortality. J Natl Cancer Inst. 2012;104:1059-1067.
13. Scagliotti GV, Hirsh V, Siena S, et al. Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. J Thorac Oncol. 2012;7:1823-1829.
14. Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363:733-742.
15. Pirl WF, Greer JA, Traeger L, et al, Depression and survival in metastatic nonsmall- cell lung cancer: effects of early palliative care. J Clin Oncol. 2012;30: 1310-1315.
16. Smith TJ, Temin S, Alesi ER, et al. American Society of Clinical Oncology provisional clinical opinion: the integration of palliative care into standard oncology care. J Clin Oncol. 2012;30:880-887.
17. Zimmermann C, Swami N, Krzyzanowska M, et al. Early palliative care for patients with advanced cancer: a cluster-randomised controlled trial. Lancet. 2014;383:1721-1730.
18. Bakitas MA, Tosteson TD, Li Z, et al. Early versus delayed initiation of concurrent palliative oncology care: patient outcomes in the ENABLE III Randomized Controlled Trial. J Clin Oncol. 2015;33:1428-1445.
19. Aapro MS. Supportive care and palliative care: a time for unity in diversity. Ann Oncol. 2012;23:1932-1934.
20. Cherny NI, Catane R, Kosmidis P. ESMO takes a stand on supportive and palliative care. Ann Oncol. 2003;14:1335-1337.
21. Davis MP, Strasser F, Cherny N, Levan N. MASCC/ESMO/EAPC survey of palliative programs. Support Care Cancer. 2014 Dec 12. Epub ahead of print.
22. Sullivan R, Peppercorn J, Sikora K, et al. Delivering affordable cancer care in high-income countries. Lancet Oncol. 2011;12:933-980.
23. Distelhorst SR, Cleary JF, Ganz PA, et al; on behalf of the Breast Health Global Initiative Global Summit on Supportive Care; Quality of Life Consensus Panel Members. Optimisation of the continuum of supportive and palliative care for patients with breast cancer in low-income and middle-income countries: executive summary of the Breast Health Global Initiative, 2014. Lancet Oncol. 2015;16:e137-e147.
24. Cardoso F, Bese N, Distelhorst SR, et al. Supportive care during treatment for breast cancer: resource allocations in low- and middle-income countries. A Breast Health Global Initiative 2013 consensus statement. Breast. 2013;25:593-605.

Keywords: cancer; palliative care; quality of life; supportive care; survival