Would You Refer This Patient With Cancer to a Palliative Care Specialist?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

In 2016, the American Society of Clinical Oncology published a guideline recommending that all patients with advanced cancer be referred to palliative care providers. This recommendation was based on a series of trials showing that palliative care, when added to standard oncology treatment, improves outcomes, including quality of life. Here, 2 oncologists, 1 of whom is also a palliative care specialist, debate the guideline and discuss how best to care for a 71-year-old woman with metastatic neuroendocrine carcinoma who has a short life expectancy but feels well and has no symptoms related to her cancer or chemotherapy.

Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial.

BACKGROUND: Based on preclinical work, we found that combination of poly (ADP-ribose) polymerase (PARP) inhibitors with drugs that inhibit the homologous recombination repair (HRR) pathway (such as PI3K inhibitors) might sensitise HRR-proficient epithelial ovarian cancers to PARP inhibitors. We aimed to assess the safety and identify the recommended phase 2 dose of the PARP inhibitor olaparib in combination with the PI3K inhibitor alpelisib in patients with epithelial ovarian cancer and in patients with breast cancer. METHODS: In this multicentre, open-label, phase 1b trial following a 3 + 3 dose-escalation design, we recruited patients aged 18 years or older with the following key eligibility criteria: confirmed diagnosis of either recurrent ovarian, fallopian tube, or primary peritoneal cancer of high-grade serous histology; confirmed diagnosis of either recurrent ovarian, fallopian tube, or primary peritoneal cancer of any histology with known germline BRCA mutations; confirmed diagnosis of recurrent breast cancer of triple-negative histology; or confirmed diagnosis of recurrent breast cancer of any histology with known germline BRCA mutations. Additional patients with epithelial ovarian cancer were enrolled in a dose-expansion cohort. Four dose levels were planned: the starting dose level of alpelisib 250 mg once a day plus olaparib 100 mg twice a day (dose level 0); alpelisib 250 mg once a day plus olaparib 200 mg twice a day (dose level 1); alpelisib 300 mg once a day plus olaparib 200 mg twice a day (dose level 2); and alpelisib 200 mg once a day plus olaparib 200 mg twice a day (dose level 3). Both drugs were administered orally, in tablet formulation. The primary objective was to identify the maximum tolerated dose and the recommended phase 2 dose of the combination of alpelisib and olaparib for patients with epithelial ovarian cancer and patients with breast cancer. Analyses included all patients who received at least one dose of the study drugs. The trial is active, but closed to enrolment; follow-up for patients who completed treatment is ongoing. This trial is registered with ClinicalTrials.gov, number NCT01623349. FINDINGS: Between Oct 3, 2014, and Dec 21, 2016, we enrolled 34 patients (28 in the dose-escalation cohort and six in the dose-expansion cohort); two in the dose-escalation cohort were ineligible at the day of scheduled study initiation. Maximum tolerated dose and recommended phase 2 dose were identified as alpelisib 200 mg once a day plus olaparib 200 mg twice a day (dose level 3). Considering all dose levels, the most common treatment-related grade 3-4 adverse events were hyperglycaemia (five [16%] of 32 patients), nausea (three [9%]), and increased alanine aminotransferase concentrations (three [9%]). No treatment-related deaths occurred. Dose-limiting toxic effects included hyperglycaemia and fever with decreased neutrophil count. Of the 28 patients with epithelial ovarian cancer, ten (36%) achieved a partial response and 14 (50%) had stable disease according to Response Evaluation Criteria in Solid Tumors 1.1. INTERPRETATION: Combining alpelisib and olaparib is feasible with no unexpected toxic effects. The observed activity provides preliminary clinical evidence of synergism between olaparib and alpelisib, particularly in epithelial ovarian cancer, and warrants further investigation. FUNDING: Ovarian Cancer Dream Team (Stand Up To Cancer, Ovarian Cancer Research Alliance, National Ovarian Cancer Coalition), Breast Cancer Research Foundation, Novartis.

Financial toxicity in gynecologic oncology.

OBJECTIVES: Financial toxicity is increasingly recognized as an adverse outcome of cancer treatment. Our objective was to measure financial toxicity among gynecologic oncology patients and its association with demographic and disease-related characteristics; self-reported overall health; and cost-coping strategies. METHODS: Follow-up patients at a gynecologic oncology practice completed a survey including the COmprehensive Score for Financial Toxicity (COST) tool and a self-reported overall health assessment, the EQ-VAS. We abstracted disease and treatment characteristics from medical records. We dichotomized COST scores into low and high financial toxicity and assessed the correlation (r) between COST scores and self-reported health. We calculated risk ratios (RR) and 95% confidence intervals (CI) for the associations of demographic and disease-related characteristics with high financial toxicity, as well as the associations between high financial toxicity and cost-coping strategies. RESULTS: Among 240 respondents, median COST score was 29. Greater financial toxicity was correlated with worse self-reported health (r = 0.47; p < 0.001). In the crude analysis, Black or Hispanic race/ethnicity, government-sponsored health insurance, lower income, unemployment, cervical cancer and treatment with chemotherapy were associated with high financial toxicity. In the multivariable analysis, only government-sponsored health insurance, lower income, and treatment with chemotherapy were significantly associated with high financial toxicity. High financial toxicity was significantly associated with all cost-coping strategies, including delaying or avoiding care (RR: 7.3; 95% CI: 2.8-19.1). CONCLUSIONS: Among highly-insured gynecologic oncology patients, many respondents reported high levels of financial toxicity. High financial toxicity was significantly associated with worse self-reported overall health and cost-coping strategies, including delaying or avoiding care.

Opioid use in gynecologic oncology in the age of the opioid epidemic: Part I - Effective opioid use across clinical settings, a society of gynecologic oncology evidence-based review.

As the only oncologists that provide both medical and surgical oncologic care, gynecologic oncologists encounter an exceptionally broad range of indications for prescribing opioids, from management of acute post-operative pain to chronic cancer-related pain to end-of-life care. If we are to balance opioid efficacy, safety and accessibility for our patients, we must be intimately familiar with appropriate clinical use of opioids in a range of settings, and engage in the national conversation around opioid misuse and how associated regulations and legislation may impact us and our patients. This article examines the appropriate use of opioids across the range of clinical settings encountered in gynecologic oncology.

Opioid use in gynecologic oncology in the age of the opioid epidemic: Part II - Balancing safety & accessibility.

As the only oncologists that provide both medical and surgical care, gynecologic oncologists encounter an exceptionally broad range of indications for prescribing opioids in clinical situations ranging from management of acute post-operative pain to chronic cancer-related pain to end-of-life care. While opioids are essential to the practice of gynecologic oncology, they can also have significant side effects and can be misused. Due to the explosive growth of opioid prescriptions and opioid-related overdoses and deaths during the first decade of the 21st century, there has been a recent concerted public health effort to prevent and treat opioid misuse through both legislation and education [1]. The first article in this two part series focused on appropriate use of opioids across clinical settings. This article addresses both the clinical and regulatory aspects of balancing opioid safety and accessibility for patients with gynecologic cancer.

Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study.

BACKGROUND: Olaparib is a poly(ADP-ribose) polymerase inhibitor and cediranib is an anti-angiogenic agent with activity against VEGF receptor (VEGFR) 1, VEGFR2, and VEGFR3. Both oral agents have antitumour activity in women with recurrent ovarian cancer, and their combination was active and had manageable toxicities in a phase 1 trial. We investigated whether this combination could improve progression-free survival (PFS) compared with olaparib monotherapy in women with recurrent platinum-sensitive ovarian cancer. METHODS: In our randomised, open-label, phase 2 study, we recruited women (aged ≥18 years) who had measurable platinum-sensitive, relapsed, high-grade serous or endometrioid ovarian, fallopian tube, or primary peritoneal cancer, or those with deleterious germline BRCA1/2 mutations from nine participating US academic medical centres. We randomly allocated participants (1:1) according to permuted blocks, stratified by germline BRCA status and previous anti-angiogenic therapy, to receive olaparib capsules 400 mg twice daily or the combination at the recommended phase 2 dose of cediranib 30 mg daily and olaparib capsules 200 mg twice daily. The primary endpoint was progression-free survival analysed in the intention-to-treat population. The phase 2 trial is no longer accruing patients. An interim analysis was conducted in November, 2013, after 50% of expected events had occurred and efficacy results were unmasked. The primary analysis was performed on March 31, 2014, after 47 events (66% of those expected). The trial is registered with ClinicalTrials.gov, number NCT01116648. FINDINGS: Between Oct 26, 2011, and June 3, 2013, we randomly allocated 46 women to receive olaparib alone and 44 to receive the combination of olaparib and cediranib. Median PFS was 17·7 months (95% CI 14·7-not reached) for the women treated with cediranib plus olaparib compared with 9·0 months (95% CI 5·7-16·5) for those treated with olaparib monotherapy (hazard ratio 0·42, 95% CI 0·23-0·76; p=0·005). Grade 3 and 4 adverse events were more common with combination therapy than with monotherapy, including fatigue (12 patients in the cediranib plus olaparib group vs five patients in the olaparib monotherapy group), diarrhoea (ten vs none), and hypertension (18 vs none). INTERPRETATION: Cediranib plus olaparib seems to improve PFS in women with recurrent platinum-sensitive high-grade serous or endometrioid ovarian cancer, and warrants study in a phase 3 trial. The side-effect profile suggests such investigations should include assessments of quality of life and patient-reported outcomes to understand the effects of a continuing oral regimen with that of intermittent chemotherapy. FUNDING: American Recovery and Reinvestment Act grant from the National Institutes of Health (NIH) (3 U01 CA062490-16S2); Intramural Program of the Center for Cancer Research; and the Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH.

Palliative Medicine Fellows' Discussions, Perceptions, and Training Regarding Medical Cannabis.

CONTEXT: Medical cannabis is increasingly considered for palliation of pain, nausea/vomiting, anorexia, and other symptoms. OBJECTIVES: We aimed to determine whether training in hospice and palliative medicine (HPM) adequately prepares fellows to counsel patients about medical cannabis. METHODS: A previously validated questionnaire was adapted for HPM fellows. Domains included fellows' practices recommending cannabis and their knowledge of its effectiveness and risks compared with standard treatments. U.S. HPM fellowships were sent surveys in 2022 and 2023. RESULTS: Forty six programs participated, 123 fellows responded (response rate of 42%) including 69% female; 55% White, and 28% Asian. Of respondents, 65% reported receiving formal training regarding medical cannabis; 57% reported discussing medical cannabis with over five patients; 23% recommended medical cannabis to more than five patients in the preceding year. Only 19%, however, felt sufficiently informed to issue cannabis-related recommendations. HPM fellows with prior training were not more likely to feel sufficiently informed to discuss cannabis (RR: 1.17; 95% CI: 0.82-1.66) or to recommend cannabis to patients (RR: 2.05, 95% CI: 0.89-4.71). Fellows rate cannabis as equally or more effective than conventional treatments for the following symptoms: anorexia/cachexia (63%), nausea/vomiting (43%), pain (25%), and neuropathic pain (21%). CONCLUSION: Most HPM fellows report formal training in the use of medical cannabis. Over half of trainees reported discussing medical cannabis with patients, but few considered themselves sufficiently informed to make cannabis-related clinical recommendations. These results suggest both a need for expanded high-quality evidence for medical cannabis in palliative care and for improved formal education for HPM fellows.

Outpatient Training During Hospice and Palliative Medicine Fellowship: A National Survey.

CONTEXT: Outpatient palliative care (PC) has strong evidence demonstrating impact across serious illnesses, resulting in growing demand for skilled outpatient PC clinicians. However, there is limited literature examining the existing state and quality of outpatient PC education during postgraduate training. OBJECTIVES: Characterize the current state of outpatient training in United States (US) Hospice and Palliative Medicine (HPM) physician fellowships and elicit perceptions regarding quality of outpatient PC education. METHODS: A cross-sectional survey of US adult HPM fellowship program directors (PDs) or their designee conducted between March and July, 2023. RESULTS: Of 161 programs, 85 participated (53% response rate) with representation across all US regions. HPM fellows spend a median of 4.8 weeks in outpatient PC compared to 24 weeks inpatient PC and 10.5 weeks in hospice settings. Over half (51%) of fellows saw outpatients from primarily one disease type with limited exposure to patients with other serious illnesses. Across programs, fellows' clinic structure, interdisciplinary team composition, and didactic experiences varied. On a 5-point rating scale, PDs reported significantly lower quality outpatient versus inpatient training (mean rating: 3.58 vs. 4.62, P<0.001) and perceived fellows as less prepared for independent outpatient practice upon graduation (mean: 4.06 vs. 4.73, P<0.001). CONCLUSION: Our survey of US HPM fellowships identified multiple gaps between outpatient and inpatient PC education and training during fellowship and raises concern about the adequacy of outpatient PC training. To prepare the HPM workforce to meet the diverse needs of seriously ill populations and ensure adequate access, outpatient PC training requires reform.

An eHealth system supporting palliative care for patients with non-small cell lung cancer: a randomized trial.

BACKGROUND: In this study, the authors examined the effectiveness of an online support system (Comprehensive Health Enhancement Support System [CHESS]) versus the Internet in relieving physical symptom distress in patients with non-small cell lung cancer (NSCLC). METHODS: In total, 285 informal caregiver-patient dyads were assigned randomly to receive, for up to 25 months, standard care plus training on and access to either use of the Internet and a list of Internet sites about lung cancer (the Internet arm) or CHESS (the CHESS arm). Caregivers agreed to use CHESS or the Internet and to complete bimonthly surveys; for patients, these tasks were optional. The primary endpoint-patient symptom distress-was measured by caregiver reports using a modified Edmonton Symptom Assessment Scale. RESULTS: Caregivers in the CHESS arm consistently reported lower patient physical symptom distress than caregivers in the Internet arm. Significant differences were observed at 4 months (P = .031; Cohen d = .42) and at 6 months (P = .004; d = .61). Similar but marginally significant effects were observed at 2 months (P = .051; d = .39) and at 8 months (P = .061; d = .43). Exploratory analyses indicated that survival curves did not differ significantly between the arms (log-rank P = .172), although a survival difference in an exploratory subgroup analysis suggested an avenue for further study. CONCLUSIONS: The current results indicated that an online support system may reduce patient symptom distress. The effect on survival bears further investigation.