Evidence from well-designed clinical trials is key to promote greater acceptance and access to palliative care
Almost a decade and a half has been gone since Temel and colleagues had published the seminal randomised clinical trial that prompted palliative care into prime time for people with advanced cancer (N Engl J Med. 2010 Aug 19;363(8):733-42 ). In that study, newly diagnosed metastatic non-small cell lung cancer patients were randomised to receive either early palliative care integrated with standard oncologic care or standard oncologic care alone. Nowadays, this study would not be approved by any ethical committee as not providing upfront palliative care in the metastatic setting is no longer acceptable in oncology: in fact, the benefits of early integration of palliative care for both patients and their caregivers in several clinical outcomes are widely supported by robust evidence and universal access is recommended by major scientific organizations (J Clin Oncol. 2024 Jul 1;42(19):2336-2357). Nevertheless, wider and timely-wise adequate access to palliative care for cancer patients still needs to be optimised and disparities reduced worldwide. Several barriers have been identified, which include negative perceptions and lack of education and training in palliative care, among others (Am J Hosp Palliat Care. 2021 Nov;38(11):1361-1377).
Attempts have been made to reduce some stereotypes associated with palliative care by turning the term into supportive care (Support Care Cancer. 2013 Dec; 21(12): 10.1007/s00520-013-1919-z). Likewise, in 2018, ESMO published a position statement in which the term patient-centered care was coined as an umbrella term to include both supportive and palliative care (Ann Oncol. 2018 Jan 1;29(1):36-43). Adding to this, there are still grey areas for interpretation, namely regarding the patients’ profile and adequate timing of referral - which negatively impact on a wider access of palliative care -, and many unanswered questions - including on whether we should reserve palliative care for patients with short prognosis only or those with complex symptoms, or we should give it upfront when cancer is diagnosed, regardless of its stage, symptom burden or patients’ needs. Therefore, research is highly needed not only in terms of interventions, but also regarding policies, organisational models and delivery.
Well-designed multicenter randomised clinical trials (RCT) are paramount to collect evidence and to improve awareness and education on palliative care. At the ESMO Congress 2024, data from three studies contributed to increase the knowledge in terms of pharmacologic interventions targeting cancer and treatment-related symptoms in areas where evidence was still scarce or inconsistent. ERICA study aimed to prevent nausea and vomiting (NV), a frequent side-effect of trastuzumab-deruxtecan that has been managed so far by extrapolating anti-emetic drug combinations used for moderate to highly emetic regimens (Abstract 1816O ) (ESMO Open. 2024 Feb; 9(2): 102195 ). This Japanese double-blind phase III placebo control study compared daily olanzapine (D1-D6) to placebo added to a standard 5-HT3 receptor antagonist and dexamethasone on D1 and observed reductions in NV rates in the delayed and persistent phases (up to 21 days). Nevertheless, tailoring the treatment according to the individual risk and type of NV was not contemplated in this trial design. Hui and colleagues conducted a second study - a multicentre double blind 4-arm RCT on agitated delirium, a frequently underdiagnosed and undertreated symptom in advanced cancer patients (Abstract 1476O ). They demonstrated that antipsychotics (haloperidol) or benzodiazepines (lorazepam) alone or in combination are better in controlling breakthrough agitation when compared with placebo. These data provide some evidence that identifying and treating delirium is better than not diagnosing nor treating it, which reinforces the need for healthcare providers education and training in palliative care. Another study by Lin and colleagues randomised 1349 patients with severe pain secondary to solid tumours to receive IV patient-controlled analgesia (IPCA) with hydromorphone (continuous infusion or bolus as needed) or conventional oral morphine (LBA61). This 3-arm multicentre open-label phase III RCT conducted in China showed that IPCA with or without continuous infusion is superior to oral morphine in terms of pain control, patient satisfaction and daily equivalent morphine consumption, with less side-effects. The results put emphasis on the role of patients’ and caregivers education which is vital for successful implementation of IPCA.
Results from these trials are certainly relevant, but further research exploring biomarkers to better tailor individual treatments and including other populations is needed. Full acceptance of palliative care will only happen when it becomes part of standard care for all cancer patients. The big question today is not if palliative care is worth the investment: it works and patients need it. The urgent question to answer is how we can operationalise it so that each patient receives the right care at the right setting by the right providers at the right timing. As healthcare professionals involved in cancer care, it is our duty to actively contribute to build a culture where palliative care is recognized, supported and valued.
