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Santiago Ponce
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FP10 - Small Cell Lung Cancer/NET (ID 231)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP10.04 - RESILIENT Part 1: Safety and Efficacy of Second-Line Liposomal Irinotecan in Patients with Small Cell Lung Cancer (ID 3657)
00:00 - 00:00 | Author(s): Santiago Ponce
- Abstract
- Presentation
Introduction
Many patients with small cell lung cancer (SCLC) develop drug resistance to first-line platinum-based chemotherapy, and second-line therapies are limited. RESILIENT (ClinicalTrials.gov identifier NCT03088813) is a two-part phase 2/3 study assessing the safety, tolerability and efficacy of liposomal irinotecan monotherapy as second-line treatment for patients with SCLC. Here we report data from part 1 of the RESILIENT study (data cut off, 2 December 2019).
Methods
RESILIENT part 1 was an open-label, single-arm study comprising dose-exploration and dose-expansion phases. Eligible patients with SCLC were aged ≥ 18 years, had progressed with platinum-based first-line therapy, had an Eastern Cooperative Oncology Group performance status score of 0 or 1, and had adequate organ function; prior exposure to immunotherapy was permitted. During dose exploration, participants received liposomal irinotecan 85 mg/m2 or 70 mg/m2 free base administered every 2 weeks; the identified recommended dose was used during dose expansion. Primary endpoints were safety and tolerability. Efficacy assessments included objective response rate (ORR), best overall response (BOR), progression-free survival (PFS), and overall survival (OS).
Results
In total, 30 patients received liposomal irinotecan in RESILIENT part 1 (women, 56.7%; median age, 61.5 years). During dose exploration, four patients who received liposomal irinotecan 85 mg/m2 experienced dose limiting toxicities, including diarrhea (n = 3) and abnormal liver function test (n = 1). Thus, this dose was not considered tolerable and enrollment into the 70 mg/m2 cohort was initiated; a total of 25 patients (platinum resistant, 40%) received liposomal irinotecan 70 mg/m2 (dose exploration, 12 patients; dose expansion, 13 patients). Among the 25 patients who received the recommended dose of 70 mg/m2, 40% had one or more grade ≥ 3 treatment-related treatment-emergent adverse events (TEAEs), most commonly diarrhea (20%), neutropenia (16%), and anemia, thrombocytopenia, asthenia and abdominal sepsis (each 8%); 8% of patients discontinued treatment owing to TEAEs. Median (95% CI) PFS was 3.98 (1.45–4.24) months and OS was 8.08 (5.16–9.82) months. ORR (complete response + partial response) was 44% and BOR was: complete response, 4%; partial response, 40%; stable disease, 28%; progressive disease, 20%; non-evaluable, 8%.Thirty patients were treated in RESILIENT part 1. Full results to be presented in the updated abstract.
Conclusion
In participants with SCLC who had progressed with platinum-based first-line therapy, liposomal irinotecan at the recommended dose of 70 mg/m2 showed promising antitumor activity and safety findings were aligned with the known safety profile. RESILIENT part 2, an ongoing, phase 3, randomized controlled trial versus topotecan will provide further data regarding the efficacy and safety of liposomal irinotecan 70 mg/m2 for the second-line treatment of patients with SCLC.
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MA08 - Advances in Biomarkers for Immune Checkpoint Blockade and Targeted Therapy in Non Small Cell Lung Carcinoma (ID 166)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 16:45 - 17:45, Scientific Program Auditorium
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MA08.04 - LIPI and Outcomes of Durvalumab as Consolidation Therapy after ChRT in Patients with Locally-Advanced NSCLC (ID 1969)
16:45 - 17:45 | Author(s): Santiago Ponce
- Abstract
- Presentation
Introduction
The lung immune prognostic index (LIPI), which combines pretreatment derived neutrophils/[leukocytes minus neutrophils] ratio (dNLR) >3 and lactate dehydrogenase (LDH) > upper limit of normal (ULN), is associated with outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICI). We aimed to assess whether pretreatment LIPI correlates with durvalumab efficacy after concurrent chemoradiotherapy in the locally advanced setting.
Methods
Multicenter retrospective study of locally advanced NSCLC patients treated with durvalumab consolidation in 21 European/US centers from 12/2015 to 5/2020. Clinical and biological data were collected before durvalumab treatment. PD-L1 expression by immunohistochemistry was also collected at diagnosis. LIPI was calculated according to previous reports and three groups were characterized: good (dNLR≤3+LDH≤ULN), intermediate (dNLR>3 or LDH>ULN) and poor (dNLR>3+LDH>ULN). The primary endpoint was progression-free survival (PFS). Response was assessed according to the clinical routine of each center.
Results
A total of 267 patients were enrolled. One hundred eighty-five (69%) patients were male, 252 (94%) smokers, with median age of 67 [range 59-73] and 223 (98%) with Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1. 260/266 (98%) were stage III, of which 96 were IIIA, 127 stage IIIB and 37 stage IIIC. 163 (63%) had non-squamous histology and 12/131 (27%) harbored driver alterations: 5 EGFR, 4 BRAF, 3 MET, 2 ALK; missing in 136 cases. PD-L1 was ≥1% in 191/233 (82%) patients both from Europe and US, missing in 34 cases. LIPI was evaluable in 143 patients: 90 were considered good (63%), 50 intermediate (35%) and 3 (2%) as poor LIPI group. dNLR >3 was found in 47/218 (22%) and LDH > ULN in 23/143 (16%) cases. Radiotherapy was delivered concurrent in 219 (82%) of cases. No differences in clinical characteristics were found between 3 LIPI groups, including the response to previous chemoradiotherapy.
With a median follow-up of 13.4 months [95% confidence interval (CI), 12-15], the median PFS was 20 months [95% CI, 12.7-not reached (NR)]. Median PFS was 7.5 months [95% CI, 3.1-NR] for poor group vs. 10.7 months [95% CI, 5.1-NR] for intermediate group vs. 19.1 months [95% CI, 11.6-NR] for good LIPI group (P=0.020). Median overall survival (OS) was NR [95% CI 47-NR] in the entire cohort and therefore considered not mature. The first objective response rate under durvalumab was 44% (111/251), being 36% (18/50) for the intermediate-poor group and 38% (33/87) for the good group with no significant differences (P=0.099). No differences in PFS and OS between groups were found regarding PD-L1 status (P=0.5 and P=0.4, respectively).
Conclusion
Pretreatment LIPI is associated with clinical outcomes in locally advanced patients treated with durvalumab as consolidation after chemoradiotherapy. This cohort is still ongoing to confirm our preliminary findings in a larger cohort.
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P48 - Small Cell Lung Cancer/NET - Chemo - IO (ID 236)
- Event: WCLC 2020
- Type: Posters
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P48.14 - RESILIENT Part 2: A phase 3 Study of Liposomal Irinotecan in Patients with Small-Cell Lung Cancer in the Second-Line Setting (ID 3485)
00:00 - 00:00 | Author(s): Santiago Ponce
- Abstract
Introduction
Small cell lung cancer (SCLC) accounts for approximately 15% of lung cancers. SCLC is usually sensitive to established first-line therapies, but many patients relapse and develop resistance to platinum-based first-line treatment. Currently, the topoisomerase 1 inhibitor topotecan is the only approved second-line therapy for SCLC in the USA and Europe. Liposomal irinotecan is an intravenous formulation that encapsulates the topoisomerase 1 inhibitor irinotecan in a lipid-bilayer vesicle, leading to prolonged circulation. The safety, tolerability and efficacy of liposomal irinotecan monotherapy in patients with SCLC who progressed with platinum-based first-line therapy is being evaluated in RESILIENT (NCT03088813), a two-part phase 2/3 study. Preliminary data from the dose-ranging part of the study (part 1) indicated that liposomal irinotecan 70 mg/m2 (free base equivalent) administered every 2 weeks was well tolerated and had promising antitumour activity.1 Here, we present the design of RESILIENT part 2, which will assess the efficacy and safety of liposomal irinotecan versus topotecan in the same patient population.
References
Paz-Ares L et al. Poster presented at the 2019 American Society of Clinical Oncology conference, May 31–June 4, 2019, Chicago, IL, USA
Methods
RESILIENT part 2 is a phase 3, open-label study with a planned sample size of 450. Participants are randomized 1:1 to intravenous liposomal irinotecan or intravenous topotecan. Liposomal irinotecan is administered at 70 mg/m2 every 2 weeks and topotecan is administered at 1.5 mg/m2 for 5 consecutive days every 3 weeks. A total of 254 patients have been randomized and received treatment to date (as of August 8, 2020). Tumour assessments are performed using the Response Evaluation Criteria in Solid Tumors version 1.1 and the Response Assessment in Neuro-oncology criteria for CNS lesions. Improvements in symptoms are measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and the European Organization for Ressearch and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13. Safety assessments include monitoring for adverse events. Overall survival is the primary endpoint of the study. Progression-free survival, objective response rate and proportion of patients reporting symptom improvement are secondary endpoints. Participants will continue study treatment until disease progression, unacceptable toxicity or study withdrawal. Participants will be followed for survival until death or study end, which is when all patients have died, withdrawn consent or are lost to follow-up.
