Nivolumab In Combination With Ipilimumab (Opdivo-Yervoy)

CADTH recommends that Opdivo in combination with Yervoy (nivolumab plus ipilimumab) should be reimbursed by public drug plans for the treatment of malignant pleural mesothelioma (MPM) if certain conditions are met. Opdivo plus Yervoy should only be reimbursed if prescribed by clinicians with experience in immuno-oncology and treating MPM and if the cost of Opdivo plus Yervoy is reduced. Opdivo plus Yervoy should only be covered to treat patients who have not received prior systemic treatment for MPM and who have good performance status at the start of treatment.

Pembrolizumab (Keytruda)

CADTH recommends that Keytruda (pembrolizumab) should be reimbursed as monotherapy for the first-line treatment of metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer if certain conditions are met. Keytruda should only be reimbursed if prescribed by clinicians with experience in immuno-oncology and treating colorectal cancer, and if the price of the drug is reduced. Keytruda should only be covered to treat patients who have not received prior treatment for metastatic MSI-H/dMMR colorectal cancer and have a good performance status at the start of treatment with pembrolizumab.

Outcomes in Elderly Patients with Glioblastoma Multiforme Treated with Short-Course Radiation Alone Compared to Short-Course Radiation and Concurrent and Adjuvant Temozolomide Based on Performance Status and Extent of Resection

(1) Background: Studies in elderly patients over the age of 65 with glioblastoma have shown survival benefits of short-course radiation therapy with concurrent and adjuvant temozolomide, making it the standard of care adopted at Juravinski Cancer Center. Our study retrospectively examines patients with GBM aged ≥ 70 at the JCC treated with short-course radiation alone compared to those treated with short-course radiation and concurrent and adjuvant TMZ, to determine if there is a difference in outcomes based on performance status. (2) Methods: A retrospective chart review was conducted at JCC using patients diagnosed with GBM in 2014–2017 (treated with the old protocol of short-course RT alone) versus those diagnosed in 2017–2019 (treated with the new protocol of short-course radiation and TMZ). Patient demographics, treatments, outcomes, and baseline KPS were analyzed. (3) Results: No clear benefit and more neurologic decline post treatment were seen in patients with borderline performance status and subtotal resection who underwent concurrent treatment with temozolomide and radiation. The addition of temozolomide was most helpful in patients with good performance status and a gross total resection. Variable outcomes were seen in patients with mixed traits. (4) Conclusions: This study suggests that performance status and extent of resection are significant determinants of patient response to treatment. In the case of elderly patients with borderline performance status and GTR or those with good performance status and STR, also described as “mixed traits”, it may be beneficial to pursue single modality treatment, ideally based on MGMT promoter methylation status as opposed to bimodality treatment in order to maintain the best QOL.

Assessment of mortality and performance status in critically ill cancer patients: A retrospective cohort study

Introduction Given clinicians’ frequent concerns about unfavourable outcomes, Intensive Care Unit (ICU) triage decisions in acutely ill cancer patients can be difficult, as clinicians may have doubts about the appropriateness of an ICU admission. To aid to this decision making, we studied the survival and performance status of cancer patients 2 years following an unplanned ICU admission. Materials and methods This was a retrospective cohort study in a large tertiary referral university hospital in the Netherlands. We categorized all adult patients with an unplanned ICU admission in 2017 into two groups: patients with or without an active malignancy. Descriptive statistics, Pearson’s Chi-square tests and the Mann-Whitney U tests were used to evaluate the primary objective 2-year mortality and performance status. A good performance status was defined as ECOG performance status 0 (fully active) or 1 (restricted in physically strenuous activity but ambulatory and able to carry out light work). A multivariable binary logistic regression analysis was used to identify factors associated with 2-year mortality within cancer patients. Results Of the 1046 unplanned ICU admissions, 125 (12%) patients had cancer. The 2-year mortality in patients with cancer was significantly higher than in patients without cancer (72% and 42.5%, P <0.001). The median performance status at 2 years in cancer patients was 1 (IQR 0–2). Only an ECOG performance status of 2 (OR 8.94; 95% CI 1.21–65.89) was independently associated with 2-year mortality. Conclusions In our study, the majority of the survivors have a good performance status 2 years after ICU admission. However, at that point, three-quarter of these cancer patients had died, and mortality in cancer patients was significantly higher than in patients without cancer. ICU admission decisions in acutely ill cancer patients should be based on performance status, severity of illness and long-term prognosis, and this should be communicated in the shared decision making. An ICU admission decision should not solely be based on the presence of a malignancy.

Clinical Effects of Stereotactic Body Radiation Therapy Targeting the Primary Tumor of Liver-Only Oligometastatic Pancreatic Cancer

AimTo investigate the efficacy and safety of stereotactic body radiotherapy (SBRT) targeting the primary tumor for liver-only oligometastatic pancreatic cancer.MethodsWe compared the efficacy and safety of SBRT plus chemotherapy with chemotherapy alone in patients with liver-only oligometastatic pancreatic cancer. The populations were balanced by propensity score-weighted and propensity score-matched analyses based on baseline variables. The primary outcome was overall survival (OS). The secondary outcomes included progression free survival (PFS), local progression, metastatic progression and symptomatic local control.ResultsThis is a retrospective study of 89 pancreatic cancer patients with liver-only oligometastasis. Overall, 34 (38.2%) and 55 (61.8%) patients received SBRT plus chemotherapy and chemotherapy alone, respectively. After propensity score matching, 1-year OS rate was 34.0% (95%CI, 17.8-65.1%) in the SBRT plus chemotherapy group and 16.5% (95%CI, 5.9-46.1%) in chemotherapy alone group (P=0.115). The 6-month PFS rate was 29.4% (95%CI, 15.4-56.1) in SBRT plus chemotherapy and 20.6% (95%CI, 8.8-48.6) in chemotherapy alone group (P=0.468), respectively. Further subgroup analysis indicated that the addition of SBRT improved OS in patients with primary tumor located in the head of pancreas (stratified HR, 0.28; 95% CI, 0.09 to 0.90) or good performance status (stratified HR, 0.24; 95% CI, 0.07 to 0.86). In terms of disease control, SBRT delayed local progression of pancreas (P=0.008), but not distant metastatic progression (P=0.56). Besides, SBRT offered significant abdominal/back pain relief (P=0.016) with acceptable toxicities.ConclusionsThe addition of SBRT to chemotherapy in patients with liver-only oligometastatic pancreatic cancer improves the OS of those with primary tumor located in the head of pancreas or good performance status. In addition, it is a safe and effective method for local progression control and local symptomatic palliation in patients with metastatic pancreatic cancer.

221 Poor performance status negatively affects survival benefit of immunotherapy in non-small cell lung cancer

BackgroundImmunotherapy has shown survival benefit as both frontline and subsequent therapy in multiple cancers. However, its efficacy in patients with poor performance status is unknown since they are excluded from the clinical trials. We conducted a retrospective study to investigate the effect of poor performance status (PS) on survival in patients with non-small cell lung cancer (NSCLC) who received immunotherapy as a subsequent line of treatment.MethodsWe reviewed the medical records of 341 patients with NSCLC receiving immunotherapy as between July 2013 and June 2018. Progression-free survival and overall survival was calculated using Kaplan-Meier curve.ResultsThe average age of patients was 66 years (range: 39–90 years), with a male predominance (57%). Majority of the patients were Caucasian (87%), followed by African-American (12%), and Asian (1%). Most of the patients were former smoker (72%), followed by current smoker (19%) and never smoker (7%). Adenocarcinoma and squamous cell carcinoma was diagnosed in 206 (60%) patients and 112 (33%) patients, respectively. The ECOG-PS was 0, 1, 2 and 3 in 46 (13%), 175 (51%), 86 (25%) and 34 (10%), respectively. Four different immunotherapies were used, namely atezolizumab in 10 (3%), durvalumab in 34 (10%), nivolumab in 152 (44%) and pembrolizumab in 144 (42%) patients. Average number of cycles of atezolizumab received by the patient was 6 (range 2–22 cycles), durvalumab 15 (range 1–29 cycles), nivolumab 11 (range 1–112 cycles), and pembrolizumab 12 (range 1–52 cycles). Patients were grouped in good performance status (ECOG 0–1) and poor performance status (ECOG ≥2). The median progression free survival (PFS) was 7 months (95% CI 6.3–8.2) in patients with good PS and 3 months (95% CI 1.8–4.6) in patients with poor performance status (p<0.001). The median overall survival (OS) for patients with good performance status was 30 months (95% CI 16.6–42.3) and 4 months (95% CI 3.2–8.1) in patients with poor PS (figure 1). Adverse effects were recorded in a total of 83 (24%) patients, 18 (5%) patients had ECOG-PS 0, 50 (14%) patients had ECOG-PS 1, 18 (4%) patients had ECOG-PS 2 and 3 (1%) patients had ECOG-PS of 3. Most common adverse effects were pneumonitis (28%), diarrhea (8%) and hypothyroidism (8%).Abstract 221 Figure 1Progression free survival (PFS) and overall survival (OS) in patients with good performance status (ECOS PS 0–1) and poor performance status (ECOG ≥2) treated with immunotherapy in NSCLCConclusionsOur data suggests that while the patients with poor PS tolerated the immunotherapy. However, poor PS was associated with significantly lower PFS and OS. Further studies are required to evaluate the effect of PS on survival in frontline immunotherapy.AcknowledgementsWe thank Dr. Saqib Abbasi for helpful discussions.Trial RegistrationN/AEthics ApprovalThe study was approved by the Institution Review Board at KUMC, #CR00009003.ReferencesN/A

Executive summary from American Radium Society’s appropriate use criteria on neurocognition after stereotactic radiosurgery for multiple brain metastases

Background The American Radium Society (ARS) Appropriate Use Criteria brain malignancies panel systematically reviewed (PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses]) published literature on neurocognitive outcomes after stereotactic radiosurgery (SRS) for patients with multiple brain metastases (BM) to generate consensus guidelines. Methods The panel developed 4 key questions (KQs) to guide systematic review. From 11 614 original articles, 12 were selected. The panel developed model cases addressing KQs and potentially controversial scenarios not addressed in the systematic review (which might inform future ARS projects). Based upon quality of evidence, the panel confidentially voted on treatment options using a 9-point scale of appropriateness. Results The panel agreed that SRS alone is usually appropriate for those with good performance status and 2–10 asymptomatic BM, and usually not appropriate for &gt;20 BM. For 11–15 and 16–20 BM there was (between 2 case variants) agreement that SRS alone may be appropriate or disagreement on the appropriateness of SRS alone. There was no scenario (among 6 case variants) in which conventional whole-brain radiotherapy (WBRT) was considered usually appropriate by most panelists. There were several areas of disagreement, including: hippocampal sparing WBRT for 2–4 asymptomatic BM; WBRT for resected BM amenable to SRS; fractionated versus single-fraction SRS for resected BM, larger targets, and/or brainstem metastases; optimal treatment (WBRT, hippocampal sparing WBRT, SRS alone to all or select lesions) for patients with progressive extracranial disease, poor performance status, and no systemic options. Conclusions For patients with 2–10 BM, SRS alone is an appropriate treatment option for well-selected patients with good performance status. Future study is needed for those scenarios in which there was disagreement among panelists.