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P. Lee
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MA 03 - Chemotherapy (ID 651)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Jin-Hyoung Kang, W. Su
- Coordinates: 10/16/2017, 11:00 - 12:30, Room 502
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MA 03.06 - Effect of 2L Ramucirumab after Rapid Time to Progression on 1L Therapy: Subgroup Analysis of REVEL in Advanced NSCLC (ID 7947)
11:00 - 12:30 | Author(s): P. Lee
- Abstract
- Presentation
Background:
In REVEL, ramucirumab+docetaxel in the second-line (2L) treatment of patients with advanced NSCLC led to improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), independent of histology. This exploratory, post-hoc analysis focuses on patients who progressed rapidly on first-line (1L), and who traditionally have a poor prognosis in the 2L setting. In REVEL, treatment benefit was observed in patients with progressive disease as their best overall response to 1L and in patients who were on 1L for only a short time (Reck M, ASCO 2017, Abstr 9079). Here, we report outcomes from patients who participated in REVEL according to their time to tumor progression (TTP) on 1L (ClinicalTrials.gov, NCT01168973).
Method:
Patients with advanced NSCLC of squamous or nonsquamous histology with disease progression during or after 1L platinum-based chemotherapy were randomized (1:1) to receive docetaxel 75 mg/m[2] and either ramucirumab 10 mg/kg or placebo on day 1 of a 21-day cycle. OS was the primary endpoint. Secondary endpoints included PFS, ORR, safety, and patient-reported quality-of-life (QoL). Response was assessed according to RECIST v1.1. QoL was assessed with the Lung Cancer Symptom Scale. TTP on 1L, defined as the time from start of 1L until progressive disease, was assessed for the REVEL intent-to-treat population.
Result:
Of 1253 patients in REVEL, 11% had TTP ≤9 weeks, 17% had TTP ≤12 weeks, and 28% had TTP ≤18 weeks on 1L therapy. Baseline characteristics of each subgroup generally were balanced between treatment arms. Efficacy, safety, and QoL outcomes by TTP are shown in the table.Outcomes in Patients From the REVEL Study by Time to Tumor Progression on First-Line Therapy
≤9 Weeks ≤12 Weeks ≤18 Weeks INTENT-TO-TREAT POPULATION Ramucirumab+Docetaxel N = 71 Placebo+Docetaxel N = 62 Ramucirumab+Docetaxel N = 111 Placebo+Docetaxel N = 98 Ramucirumab+Docetaxel N = 182 Placebo+Docetaxel N = 172 Median OS, months (95% Confidence Interval [CI]) 8.28 (5.19, 10.84) 4.83 (3.09, 6.90) 9.10 (6.70, 10.84) 5.78 (4.30, 7.49) 8.51 (6.97, 9.95) 5.95 (4.44, 6.97) Unstratified Hazard Ratio (HR) (95% CI) 0.69 (0.47, 1.01) 0.74 (0.54, 1.00) 0.80 (0.63, 1.01) 12-month survival rate, % (95% CI) 47 (35, 58) 32 (20, 44) 34 (25, 43) 23 (15, 32) 30 (23, 37) 24 (18, 31) 18-month survival rate, % (95% CI) 20 (11, 31) 12 (5, 24) 17 (10, 26) 13 (6, 22) 17 (11, 23) 13 (8, 20) Median PFS, months (95% CI) 3.01 (2.66, 4.07) 1.48 (1.41, 1.87) 3.61 (2.76, 4.21) 1.61 (1.45, 2.60) 3.22 (2.79, 4.14) 1.61 (1.48, 2.60) Unstratified HR (95% CI) 0.69 (0.48, 0.98) 0.73 (0.55, 0.97) 0.72 (0.58, 0.89) ORR (complete response [CR]+partial response [PR]), %, (95% CI) 18.3 (10.1,29.3) 3.2 (0.4, 11.2) 18.9 (12.1, 27.5) 9.2 (4.3, 16.7) 19.2 (13.8, 25.7) 10.5 (6.3, 16.0) Disease Control Rate (CR+PR+stable disease), % (95% CI) 50.7 (38.6, 62.8) 30.6 (19.6, 43.7) 49.5 (39.9, 59.2) 37.8 (28.2, 48.1) 50.5 (43.1, 58.0) 36.0 (28.9, 43.7) Average Symptom Burden Index, time to deterioration HR (95% CI) 0.60 (0.30, 1.22) 0.49 (0.27, 0.88) 0.74 (0.49, 1.12) Total Score Lung Cancer Symptom Scale, time to deterioration HR (95% CI) 0.89 (0.45, 1.78) 0.71 (0.41, 1.23) 0.90 (0.60, 1.36) SAFETY POPULATION Ramucirumab+Docetaxel N = 70 Placebo+Docetaxel N = 61 Ramucirumab+Docetaxel N = 109 Placebo+Docetaxel N = 97 Ramucirumab+Docetaxel N = 179 Placebo+Docetaxel N = 171 Any Treatment-Emergent Adverse Event (TEAE), n (%) 67 (95.7) 58 (95.1) 105 (96.3) 92 (94.8) 173 (96.6) 159 (93.0) Grade ≥3 50 (71.4) 46 (75.4) 80 (73.4) 69 (71.1) 134 (74.9) 113 (66.1) TEAE leading to discontinuation 4 (5.7) 2 (3.3) 5 (4.6) 3 (3.1) 13 (7.3) 6 (3.5) TEAE leading to dose adjustment 24 (34.3) 19 (31.1) 39 (35.8) 28 (28.9) 70 (39.1) 47 (27.5) TEAE leading to death 5 (7.1) 4 (6.6) 7 (6.4) 6 (6.2) 9 (5.0) 8 (4.7) TESAE 25 (35.7) 30 (49.2) 46 (42.2) 46 (47.4) 80 (44.7) 71 (41.5)
Conclusion:
Efficacy, toxicity, and QoL outcomes among ramucirumab+docetaxel patients who have aggressive disease with rapid TTP on 1L therapy appear consistent with the intent-to-treat population. The benefit/risk profile for these rapid progressors suggests that such patients may derive meaningful benefit from ramucirumab+docetaxel in the 2L setting.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-071 - Randomized Phase 1b/3 Study of Erlotinib + Ramucirumab in Untreated EGFR Mutation-Positive Stage IV NSCLC: Phase 1b Outcomes (ID 8468)
09:30 - 16:00 | Author(s): P. Lee
- Abstract
Background:
Despite the likelihood of an initial response to an EGFR TKI, NSCLC patients with an activating EGFR mutation eventually develop disease progression. Anti-angiogenic agents in combination with an EGFR TKI may provide additional benefit in EGFR-mutant NSCLC, but additional studies are needed to confirm the benefit.
Method:
This ongoing phase 1b/3 study (NCT02411448; RELAY) enrolled patients with previously untreated stage IV NSCLC, ECOG PS 0-1, and an activating EGFR mutation (exon 19 deletion or exon 21 L858R substitution). In part A (phase 1b), patients received ramucirumab (anti-VEGFR2 antibody) 10 mg/kg intravenously on day 1 of a 14-day cycle and oral erlotinib at 150 mg/day. Treatment continued until disease progression or unacceptable toxicity. The primary objective of part A was to assess safety and tolerability, in terms of dose-limiting toxicities (DLTs) during the first two cycles of therapy, and to determine the recommended dose for Part B (phase 3). Data cutoff was 31-May-2017.
Result:
Fourteen patients were enrolled and treated in part A. Two patients discontinued prior to completion of cycle 2, due to non-DLT adverse events of grade 2 interstitial pneumonia and grade 1 hemoptysis and were therefore not eligible for DLT assessment. Of the 12 DLT-evaluable patients (Japan, n=6; US/Europe, n=6), median age was 72 years (range 51-83), 83% were female, and 75% had ECOG PS of 1. Median duration of therapy was 64.3 weeks (interquartile range [IQR] 19.5-89.0) with ramucirumab and 68 weeks (IQR 44-95) with erlotinib. Treatment-emergent adverse events (TEAEs) occurred in all patients, most commonly rash (100%), diarrhea (92%), paronychia (67%), hypertension (58%), and dry skin (58%). Ten (83%) patients experienced grade 3 TEAEs (hypertension [n=4], rash [n=3], diarrhea [n=2], neutropenia, conjunctivitis, elevation of alanine aminotransferase [DLT; resolved within 4 days], and elevation of aspartate aminotransferase). No serious or grade 4-5 adverse events occurred. Median PFS was 17.1 months (95% CI 8.8-NR; 50% censored) and the PFS survival rate at 21-months was 46.9%. Five patients remain on study treatment.
Conclusion:
Ramucirumab plus erlotinib demonstrated encouraging clinical activity with no unexpected toxicities in Part A. Randomization into Part B began in January-2016, maintaining the dose of ramucirumab at 10 mg/kg Q2W with oral erlotinib at 150 mg/day.
