Marvelous objective response of low dose radiotherapy plus ICIs for extended stage small cell lung cancer.

e21097 Background: Immune checkpoint inhibitors (ICIs) has limited efficacy with unsatisfactory objective response for extensive stage small cell lung cancer (ES-SCLC). In this respective study, efficacy and toxicities of low dose radiotherapy (LDRT) plus ICIs for pretreated failure ES-SCLC has been evaluated, and marvelous objective response has been observed. Methods: From March 2018 to Dec 2019, ten pretreated failure ES-SCLC patients received LDRT (8-20Gy/2-10f, BED10 9.5-24Gy) for lesions located in lung or other sites plus ICIs (Nivolumab, Pembrolizumab, Ipilimumab, Durvalumab, and Sintilimab) were enrolled. Two patients received concurrent chemotherapy of etoposide plus cisplatin or albumin-bound paclitaxel monotherapy. ICIs were given within 7 days after LDRT. Efficacy, toxicities, and lung cancer symptom scale (LCSS) scores were evaluated. Results: Thirteen lesions (ten located in lungs, and the others located in adrenal gland, axillary lymph node, and abdomen) received LDRT. The gross tumor volume and planning target volume were 32.56 cc-430.19cc and 73.74 cc-771.41 cc, respectively. Eleven lesions did not receive radiotherapy. The objective response rate (ORR) of whole patients was 90% (9/10). The ORR and disease control rate (DCR) of radiated lesions were 92.3% (12/13) and 100% (13/13), compared to 9.1% (1/11) and 18.2% (2/11) for no radiated lesions. Volume shrinkage rates (VSRs) of radiated lesions were 35.16% to 95.91% (13.75cc-277.02cc), and 61.5% (8/13) of radiated lesions reduced more than 80%. VSRs for radiated lesions with volume > 100cc were 63.07% to 95.91% (122.38cc-277.02cc). LCSS improved significantly after treatment (465±13.02 vs. 380±17.8, p= 0.0013). Lymphocyte declined initially and then recovered in patients with disease not progressed, on the contrary, it declined continuously in patients with disease progressed. The most popular toxicities were lymphopenia (70%) and anemia (60%). Grade 3-4 toxicities included lymphopenia (40%), thrombocytopenia (20%), anemia (20%), and granulocytopenia (10%). Conclusions: LDRT might enhance the effectiveness of ICIs greatly for tumor lesions, and radiotherapy should be considered to be given initially for ES-SCLC received ICIs treatment.

Quality of life with second or third line nab-paclitaxel-based regimens in advanced non-small-cell lung cancer

Aim: Evaluate quality of life (QoL) in patients with advanced non-small cell lung cancer treated with second or third line nab-paclitaxel ± durvalumab. Patients & methods: Longitudinal QoL was assessed using Lung Cancer Symptom Scale, EuroQoL Five-Dimensions Five-Levels and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core. Results: QoL was generally stable through eight treatment cycles (both arms). Clinically meaningful improvement from baseline was noted in Lung Cancer Symptom Scale (overall constitutional score and three-item index [ nab-paclitaxel + durvalumab]) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core (global health status/QoL and emotional functioning [both arms] and pain [ nab-paclitaxel + durvalumab]) analyses. EuroQoL Five-Dimensions Five-Levels domains were stable/improved or completely resolved at least once in 19–56% and 9–51% of patients, respectively. Conclusion: While QoL trends were promising, additional data are required to support these regimens in this setting.

“If you don’t ask, you won’t know”: Do patient-reported outcome (PRO) instruments capture the symptom experience of patients treated with immune checkpoint inhibitors (ICIs)?

11579 Background: PROs are increasingly used as a key tool in patient-focused treatment decisions. However, many cancer PROs were designed to capture the patient experience of those treated with chemotherapeutic agents. Less is known about the utility of PRO instruments in assessing symptoms from ICIs. Methods: We systematically searched the literature to identify peer-reviewed publications that reported PROs for patients receiving ICIs. We excluded case reports/series, narrative reviews, and publications without original data. We then selected the studies that compared ICIs to cytotoxic chemotherapy. Clinician-documented adverse events (AEs) occurring in at least 10% of patients in a study arm were extracted and examined for concordance with symptoms included in the PROs administered to study patients. Results: Of 1,450 identified studies, eight met criteria for inclusion. Seven assessed PROs with the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), six used the EuroQOL EQ-5D, and one used the Lung Cancer Symptom Scale (LCSS). Across the studies, fatigue, nausea, vomiting, appetite loss, diarrhea, constipation, pruritus, rash, and pyrexia were among the most common clinician-documented AEs. Of these AEs, six are directly correlated with questions on the PRO instruments, and three (pruritus, rash, and pyrexia) are not. AEs with corresponding PRO questions were more common in chemotherapy patients. Pruritus, rash, and pyrexia – AEs without corresponding PRO questions – were more common in patients treated with ICIs (see Table). Conclusions: Existing PRO instruments do not specifically query important symptoms associated with ICIs, underscoring the need to revise the instruments to more appropriately reflect the toxicity profiles of novel agents. [Table: see text]

Maintenance Defactinib Versus Placebo After First-Line Chemotherapy in Patients With Merlin-Stratified Pleural Mesothelioma: COMMAND—A Double-Blind, Randomized, Phase II Study

PURPOSE Inhibition of focal adhesion kinase has been shown to selectively kill mesothelioma cells that express low levels of moesin-ezrin-radixin-like protein (merlin). On this basis, we designed a randomized, phase II trial to investigate whether defactinib as maintenance therapy after standard first-line chemotherapy could improve progression-free survival (PFS) in patients with malignant pleural mesothelioma (MPM). METHODS This global, double-blind, randomized, placebo-controlled trial was conducted in patients with advanced MPM and disease control after at least four cycles of first-line chemotherapy. Patients were stratified for merlin and then randomly assigned (in a 1:1 fashion) to receive either oral defactinib or placebo until disease progression, unacceptable toxicity, or withdrawal occurred. The coprimary end points were PFS and overall survival (OS). Quality of life (QoL) was assessed using the Lung Cancer Symptom Scale for Mesothelioma tool. RESULTS Three hundred forty-four patients were randomly assigned to receive either defactinib (n = 173) or placebo (n = 171). The median PFS was 4.1 months (95% CI, 2.9 to 5.6 months) for defactinib versus 4.0 months (95% CI, 2.9 to 4.2 months) for placebo. The median OS was 12.7 months (95% CI, 9.1 to 21 months) for defactinib versus 13.6 months (95% CI, 9.6 to 21.2 months) for placebo (hazard ratio, 1.0; 95% CI, 0.7 to 1.4). Although shorter survival for both defactinib- and placebo-treated patients was observed, in the patients who had merlin-low MPM compared with the patients who had merlin-high MPM, there were no statistical differences in response rate, PFS, OS, or QoL between the treatment groups. The most common grade 3 or worse adverse events were nausea, diarrhea, fatigue, dyspnea, and decreased appetite. CONCLUSION Neither PFS nor OS was improved by defactinib after first-line chemotherapy in patients with merlin-low MPM. Defactinib cannot be recommended as maintenance therapy for advanced MPM.

Symptom Burden in Extensive Disease Small Cell Lung Cancer (ED-SCLC): A prospective, observational study in U.S. community practices.

196 Background: There is a paucity of data describing the effect of treatment on symptom burden and health status for patients with ED-SCLC receiving care in US community oncology centers. This study explores ED-SCLC patient-reported outcomes independently for either first-line (1L), second-line (2L) or third-line (3L) therapy. Methods: CA209-118 is a prospective observational study of adult patients with lung cancer, including patients with ED-SCLC, in 70 US community practices enrolled between 2014-2017. Participants completed the Lung Cancer Symptom Scale (LCSS) and Euro-QoL 5-D (EQ-5D) utility index and visual analog scale (VAS) at the start of 1L, 2L, or 3L treatment and at follow-up visits. The LCSS is summarized in 3 scales: LCSS total scale which ranges from 0 – 100, average symptom burden scale (ASBI) ranging from 0 – 100, and a three-item global scale (3-IGI) ranging from 0 – 300 (lower scores reflect reduced burden). The EQ-5D scale is a preference based measure of health status with higher scores reflecting better quality and ranges from 0 to 1.0 (index) or 0 – 100 (VAS). LCSS and EQ-5D values at 60 days were predicted in a repeated measures model for patients having a score at baseline and at least 1 follow-up. Results: The mean LCSS and EQ-5D scores at the start of each line of therapy and predicted 60 day change are presented in the table . 60-day improvement was observed only for appetite and cough in 1L. A slight declining trend was seen in 2L and 3L. Conclusions: Patients with ED-SCLC treated in the community reported a high symptom burden at the start of each line of therapy which did not diminish throughout 60 days of treatment. [Table: see text]

Patient-reported outcomes in PD-1/PD-L1 inhibitor registration trials: FDA analysis of data submitted and future directions.

134 Background: Patient-reported outcome measures (PROs) can capture the patient’s experience with disease and treatment. Anti-PD-1/PD-L1 therapies have unique symptomatic side effects; PRO data can help to better understand the patient experience on therapy. Health-related quality of life (HRQL) components most impacted by therapy include disease symptoms, symptomatic toxicity and physical function. Methods: We reviewed FDA registration trials for 5 immunotherapy agents (anti-PD-1/PD-L1) to evaluate trial design and PRO assessment. We assessed whether the PRO strategy assessed physical function and symptomatic immune-related adverse events (irAEs) by reviewing whether trials used a well-defined physical function domain and 8 symptoms related to irAEs reported in product labels (fatigue, diarrhea, cough, shortness of breath, musculoskeletal pain, rash, pruritis and fever). Results: Data from 25 trials across 7 disease types and 1 tumor agnostic indication were evaluated. Of these, 13 were randomized and 22 were open label. Eighteen of 25 contained PRO assessments and all 18 used > 1 instrument. The most common instruments were the EQ-5D (N = 17), followed by EORTC QLQ-C30 (N = 15). Disease-specific PRO tools were included in 8 trials (5 lung, 1 head and neck, 1 melanoma and 1 renal cell), consisting of modules or scales from EORTC (N = 5), FACIT (N = 2) or the Lung Cancer Symptom Scale (N = 1). Sixty percent of the trials (15/25) used an instrument that contained a well-defined physical function (PF) domain. No trial used a PRO strategy assessing all 8 selected symptoms related to irAEs. Conclusions: Collection of PRO data in anti-PD-1/PD-L1 trials submitted to FDA was variable, and did not consistently assess treatment related symptoms and physical function. Use of a HRQL tool with well-defined functional scales supplemented by item banks or libraries to incorporate symptoms associated with irAEs may improve understanding of the patient experience while receiving anti-PD-1/PD-L1 treatment. These data, along with other important clinical data such as hospitalizations, ER visits and supportive care medications can inform the benefit risk assessment for regulatory purposes.

Approach to offering remote support to mesothelioma patients: The Mesothelioma Survivor Project.

82 Background: From the moment of diagnosis, malignant mesothelioma (MM), decreases health-related quality-of-life (QOL) in patients and their caregivers. In addition to symptoms of disease, aggressive treatments such as surgery, radiation, and chemotherapy can cause extreme side effects – specifically, chemotherapy is associated with chronic fatigue, unremitting nausea, vomiting, and systemic pain. These side effects of treatments can be burdensome enough to lead to noncompliance or outright refusal of continuation of care.[1] Data from 13 frequently cited QOL studies focus on chest pain and shortness of breath as the two chief symptoms of pleural mesothelioma. The largest QOL study to date enrolled 495 patients, evaluated MM using the LCSS (lung cancer symptom scale). Investigators reported MM’s most common symptoms as: fatigue (94%), dyspnea (89%), loss of appetite (86%), chest pain (85%), cough (75%), and hemoptysis (24%). In addition, mesothelioma has a number of emotional consequences. A study by the British Lung Foundation (BLF) reported significant impairment of emotional function and/or emotional state in patients with mesothelioma and their family members.[2] Methods: The platform for the support group was remote, consisting of both online and telephone domains. Participants would utilize both online and phone systems during sessions, held once a week for a total of 6 weeks. Sessions were guided and kept closed, available only to those affected by mesothelioma. Participants completed surveys after each support group. Session summaries and follow-up information were provided online after support meetings. Results: Using a 0-5 Likert Scale, consistent attendees reported support groups as very helpful (4). Irregular attendees had mixed feelings ranging from extremely helpful (5) to neutral (3). 80% of attendees participated in support groups prior to ours. Conclusions: Active participation in a guided and closed support group allowed participants to share their experiences and concerns about their diagnoses, comfortably – supporting transition beyond active-treatment. The online portion of the platform was helpful in assuaging common negative concerns.