Virtual Library
Start Your Search
D. Waterhouse
Author of
-
+
MINI 03 - PD1 Axis Inhibition and EGFR (ID 101)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:L. Gandhi, Y. Ohe
- Coordinates: 9/07/2015, 16:45 - 18:15, Four Seasons Ballroom F1+F2
-
+
MINI03.07 - Clinical Attributes of Lung Cancer in US Community Oncology Practice: Implications for Immunotherapy (ID 733)
17:20 - 17:25 | Author(s): D. Waterhouse
- Abstract
- Presentation
Background:
The majority of lung cancer in the US is treated in the community. A prospective cohort study of stage IV non-small cell lung cancer (NSCLC) and extensive disease small cell lung cancer (ED SCLC) is being conducted in 70 US community oncology practices (Figure) to assess current standards of care (SOC) and outcomes in anticipation of immunotherapy as a new treatment modality. This study establishes a historical comparator cohort in a “pre-immunotherapy era” of lung cancer treatment. Figure 1
Methods:
Patients with stage IV NSCLC and ED SCLC, at any point in their care, with documented dates of diagnosis and prior treatment, are eligible for inclusion. Patients are followed prospectively for 36 months or until death, with data abstraction from medical records into electronic case report forms. Patient-reported outcomes are prospectively collected, as are archival tumor tissue and serial blood samples from consenting patients for molecular profiling studies.
Results:
This early analysis focused on patient clinical attributes and tumor sample characteristics of relevance to non-clinical trial patient populations and to biomarker testing (Table). Of 1,183 cases enrolled to date, at enrollment 17.6% were ECOG performance status (PS) 2 or 3, 18.8% of patients had brain metastases, 22.2% were on systemic steroids, 6.7% had history of a specific autoimmune condition, and 49.5% had had tissue samples from core needle or surgical specimens.Figure 1
Conclusion:
Many immunotherapy clinical trials exclude patients with brain metastases, certain steroid use, poor PS, and autoimmune disease, yet a substantial proportion of community-based lung cancer patients present with these attributes. Approximately half of advanced stage patients have tissue specimens amenable to current SOC biomarker testing. Efforts to develop additional biomarker tests for lung cancer patients need to consider the reality of limited tissue sample availability in the community setting.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
ORAL 02 - PD1 Axis Immunotherapy 2 (ID 87)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 2
- Moderators:E.B. Garon, H.J. Ross
- Coordinates: 9/07/2015, 10:45 - 12:15, Four Seasons Ballroom F1+F2
-
+
ORAL02.01 - Phase 3, Randomized Trial (CheckMate 017) of Nivolumab (NIVO) vs Docetaxel in Advanced Squamous (SQ) Cell Non-Small Cell Lung Cancer (NSCLC) (ID 736)
10:45 - 10:56 | Author(s): D. Waterhouse
- Abstract
- Presentation
Background:
Treatment options for patients with advanced SQ NSCLC who fail platinum-based doublet chemotherapy (PT-DC) are limited. NIVO, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor, demonstrates activity across NSCLC histologies and is approved in the US for treatment of metastatic SQ NSCLC with progression on or after platinum-based chemotherapy. We report results from a randomized, open-label, global phase 3 study (CheckMate 017; NCT01642004) comparing NIVO vs docetaxel in patients with previously treated SQ NSCLC and disease progression during/after one prior PT-DC regimen.
Methods:
Patients (N=272) were randomized 1:1 to receive either NIVO 3 mg/kg every 2 weeks (Q2W; n=135) or docetaxel 75 mg/m[2] Q3W (n=137) until disease progression or discontinuation due to toxicity or other reasons. For NIVO patients, treatment after initial progression was permitted at the investigator’s discretion, per protocol criteria. The primary objective was overall survival (OS). Secondary objectives included investigator-assessed objective response rate (ORR; per RECIST v1.1), progression-free survival (PFS), efficacy by PD-L1 expression (PD-L1 testing not required for enrollment), patient-reported outcomes (PRO), and safety. PRO analyses are presented in a separate abstract.
Results:
Treatment with NIVO led to 41% reduction in risk of death (hazard ratio [HR]=0.59; 95% CI: 0.44, 0.79; P=0.00025) and improved ORR (20% vs 9%; P=0.0083) and PFS (HR=0.62; 95% CI: 0.47, 0.81; P=0.0004) vs docetaxel (Table). Twenty-eight patients were treated with NIVO beyond initial progression, nine of whom demonstrated a non-conventional pattern of benefit (ie, reduction in target lesions with simultaneous appearance of new lesions, initial progression followed by tumor reduction, or no further progression for ≥2 tumor assessments). Across pre-specified cut-points (1%, 5%, and 10%), PD-L1 expression was neither prognostic nor predictive of benefit. OS HRs favored NIVO across most predefined patient subgroups. Grade 3–4 drug-related adverse events (AEs) were reported in 7% (9/131) of NIVO and 55% (71/129) of docetaxel patients. Grade 3–4 drug-related select AEs are shown below (Table). No deaths were related to NIVO vs 3 docetaxel-related deaths. Figure 1
Conclusion:
CheckMate 017 achieved its primary objective, demonstrating clinically superior and statistically significant OS with NIVO vs docetaxel in patients with advanced, previously treated SQ NSCLC. Benefit was seen regardless of PD-L1 status. The safety profile of NIVO 3 mg/kg Q2W is favorable vs docetaxel and consistent with prior studies. AEs were manageable with established guidelines. NIVO represents a new standard of care in this patient population. Updated OS and safety data will be presented.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
ORAL02.02 - Safety and Efficacy of Nivolumab in an Ongoing Trial of a PD-L1+/- Patient Population with Metastatic Non-Small Cell Lung Cancer (ID 851)
10:56 - 11:07 | Author(s): D. Waterhouse
- Abstract
- Presentation
Background:
Nivolumab (NIVO), a fully human IgG4 programmed death-1 (PD-1), immune checkpoint inhibitor antibody, has demonstrated durable responses and tolerability in heavily pretreated patients with advanced non-small cell lung cancer (NSCLC). NIVO was recently approved for the treatment of patients with metastatic squamous (SQ) NSCLC with progression on or after platinum-based chemotherapy. Conducted mostly in community-based oncology centers, this ongoing trial explores the safety of NIVO in patients with previously-treated PD-L1[+/-] metastatic SQ or non-squamous (NSQ) NSCLC.
Methods:
Eligible patients are enrolled in 4 subgroups: 1) SQ, performance status (PS) 0–1, ≥2 prior therapies; 2) SQ, PS 0–1, 1 prior therapy; 3) NSQ, PS 0–1, ≥1 prior therapy; and 4) SQ or NSQ, PS 2, ≥1 prior therapy. Patients with both PD-L1[+] and PD-L1[-] tumors are eligible. Patients receive NIVO 3 mg/kg IV (60 minutes) Q2W either until progressive disease (PD)/unacceptable toxicity (Cohort A) or for 1 year with the possibility of retreatment upon disease progression (Cohort B). Primary objective is to estimate incidence of high-grade (CTCAE v4.0 Grade 3–4 and 5), select treatment-related adverse events (STRAEs); exploratory efficacy assessments include ORR, PFS, and OS.
Results:
From 4/16/14 to 12/31/14, 824 patients were treated and have demographic and safety data available; 483 patients remained on study as of 12/31/2014. 395 patients had evaluable radiographic tumor assessments at first assessment (Week 9). Demographics, safety, and tumor response by PD-L1 status are reported. Figure 1
Conclusion:
Safety and tolerability are consistent with prior NIVO experience and no new safety signals have been identified in this trial of SQ/NSQ NSCLC patients. Immune-related toxicities are manageable in a community practice setting using previously-developed safety algorithms. The frequency of STRAEs of interest was similar between patients with PS 0–1 and those with PS 2. Early data from this large, multicenter trial suggests that patients with pretreated advanced NSCLC benefit from NIVO therapy regardless of tumor PD-L1 status, histology type, and PS status.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
-
+
P1.01-077 - First-Line Nivolumab + Nab-Paclitaxel + Carboplatin (C) in Advanced NSCLC (ID 1565)
09:30 - 09:30 | Author(s): D. Waterhouse
- Abstract
Background:
Nivolumab, an anti-PD-1 inhibitor, has demonstrated anti-tumor activity in several solid tumors and is approved for unresectable/metastatic melanoma and disease progression following ipilimumab, and if BRAF V600 mutation positive, a BRAF inhibitor; and for metastatic squamous NSCLC in patients with progression on/after platinum-based chemotherapy. Combining a taxane, which can act as a cytotoxic and an immunomodulator, with an immune checkpoint inhibitor has demonstrated improved outcomes over chemotherapy alone in NSCLC. First-line nivolumab and solvent-based paclitaxel plus C (sb-P/C) resulted in a 43% overall response rate and a median progression-free survival of 31 weeks in an interim analyses from a phase I trial in patients with advanced NSCLC (Antonia et al. Presented at ASCO 2014 [Abstract 8113]). nab-Paclitaxel (nab-P) based therapy has demonstrated improved efficacy over standard treatment in pancreatic and breast cancers, and nab-P plus carboplatin (nab-P/C) significantly improved the primary endpoint (ORR) vs sb-P/C in a phase III trial of patients with advanced NSCLC (Socinski et al. J Clin Oncol. 2012;30:2055-2062) and does not requires immunosuppressive premedication. This phase I, open-label, 6-arm, multicenter trial, will evaluate safety of nivolumab with nab-P in 3 cancer types: advanced NSCLC (+ C), advanced pancreatic cancer (± gemcitabine), and metastatic breast cancer; 2 arms in each disease. The study design for the NSCLC portion is described below.
Methods:
Eligibility criteria include histologically/cytologically confirmed stage IIIB/IV NSCLC, no prior chemotherapy for metastatic disease, prior adjuvant chemotherapy allowed providing completion >12 months before study entry, ECOG PS 0-1, adequate organ function, and preexisting peripheral neuropathy grade <2. NSCLC patients will be treated in 2 arms: 4 cycles of nab-P 100 mg/m[2] on days 1, 8, and 15 plus C AUC 6 on day 1 of a 21 day cycle with nivolumab 5 mg/kg on day 15 starting at cycle 1 or the same nab-P/C regimen with nivolumab 5 mg/kg on day 15 starting at cycle 3. In both arms, nivolumab monotherapy will begin at cycle 5. Part 1 will assess the dose-limiting toxicities (DLTs) of the nivolumab dose with nab-P/C (≈ 6 patients/arm). If deemed safe, the treatment arms may be expanded using the recommended part 2 dose with an additional ≈ 14 patients/arm (total of 20 nivolumab-treated patients/arm) to further assess safety and tolerability as well as anti-tumor activity. Patients will be allowed to continue nivolumab treatment beyond RECIST 1.1 disease progression (physician discretion). ClinicalTrials.gov number NCT02309177. Figure 1 .
Results:
Not applicable
Conclusion:
Not applicable
