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David James Stewart
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MA 10 - Immunotherapy I (ID 664)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:S. Wang, Robert Pirker
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 303 + 304
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MA 10.02 - Nab-Paclitaxel + Durvalumab as Second- or Third-Line Treatment of Advanced NSCLC: Results from ABOUND.2L+ (ID 8682)
11:05 - 11:10 | Author(s): David James Stewart
- Abstract
- Presentation
Background:
Chemotherapy may enhance immunotherapeutic effects by causing tumor antigen release, which primes the immune system to kill tumor cells. Early clinical data on nab-paclitaxel + carboplatin in combination with immune checkpoint inhibitors (ICI) demonstrated promising activity without compounding toxicities in patients with non-small cell lung cancer (NSCLC). ABOUND.2L+ evaluated nab-paclitaxel–based regimens in previously treated patients with advanced NSCLC. Here we report the efficacy and safety of nab-paclitaxel + durvalumab as second/third-line treatment.
Method:
Patients with advanced NSCLC were assigned to receive second/third-line (immunotherapy allowed in prior line, including platinum doublet combination) nab-paclitaxel 100 mg/m[2] on days 1 and 8 + durvalumab 1125 mg on day 15, in 21-day cycles, administered until unacceptable toxicity/progression per immune-related RECIST v1.1. Primary endpoint is progression-free survival (PFS). Secondary endpoints are overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety.
Result:
Seventy-nine patients were enrolled. Median age was 63 years, 68% of patients were male, 23% had Eastern Cooperative Oncology Group performance status of 0, and 70% had nonsquamous NSCLC; 11% of patients received prior ICIs. Median PFS (Table) and OS were 4.5 (3.4-5.8) months and NE (7.3-NE). ORR was 27% (1 complete response) and DCR was 71%. Grade 3/4 treatment-emergent adverse events of special interest occurring in ≥ 5% of patients included neutropenia (6%) and dyspnea (5%); grade 3/4 peripheral neuropathy and anemia each occurred in 4% of patients. Median treatment duration was 24 weeks; median number of treatment cycles was 7. For nab-paclitaxel and durvalumab, median dose intensities were 59.05 mg/m[2]/week and 326.61 mg/week, respectively; median percentages of per-protocol dose were 88.58% and 87.10%.
Conclusion:
The combination of durvalumab with nab-paclitaxel demonstrated antitumor activity with manageable toxicity in the second/third-line setting. Further details will be presented. NCT02250326Nab-P Durva Median PFS (range), months Overall (n = 79) 4.5 (3.4-5.8) ICI pretreated (n = 9)[a] ICI naive (n = 69)[a] 6.9 (1.4-NE) 4.4 (3.0-5.7) Squamous (n = 23)[a] Nonsquamous (n = 55)[a] 5.9 (3.0-7.8) 4.2 (2.9-5.7) ICI, immune checkpoint inhibitor; NE, not estimable; PFS, progression-free survival. [a] Data pending for 1 patient.
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OA 11 - Reducing Burden: Patient-Centered Care (ID 682)
- Event: WCLC 2017
- Type: Oral
- Track: Nursing/Palliative Care/Ethics
- Presentations: 1
- Moderators:Beth Ivimey, E. Bernicker
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 313 + 314
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OA 11.06 - Lung Cancer Diagnosis and Assessment as a System Design Problem: Creating an Award Winning Program with Patient Advocates as Co-Designers (ID 10203)
11:55 - 12:05 | Author(s): David James Stewart
- Abstract
- Presentation
Background:
Lung cancer continues to have a high mortality in Canada, with many patients presenting with advanced stage disease. The Ottawa Hospital (TOH) used a learning health systems (LHS) approach to redesign regional diagnostic processes to reduce the overall time from presentation with a suspicious lung mass to diagnosis and treatment. As previously published by our group, an LHS approach is driven by feedback utilizing operational and clinical information to drive system optimization and innovation. TOH is the only provider of cancer services for a population of 1.3 million people in eastern Ontario and hence the need for an integrated patient journey from regional health facility to tertiary care centre was identified. Patient advocates have been incorporated as key members of the LHS from inception to implementation to post-implementation review.
Method:
The Ottawa Health Transformation model (OHTM) was developed as a means of operationalizing a LHS. A kick off meeting brought together cancer patients and their families to map out existing processes and document the patient experience. A regional lung cancer Community of Practice (CoP) of clinical and non-clinical stakeholders was then established to guide and approve the work of a core transformation team. The team had patient and family advocates as key members and they were tasked with identifying appropriate wait time targets and vetting proposed processes. A consensus approach was used to address process barriers, resistance to change and conflicting priorities in regular meetings spanning over two years. Commercially available software was used to track patient progress through the diagnostic process and to report real time metrics to the transformation team.
Result:
The project operationalized lung cancer diagnostic pathway guidance and optimized patient flow from referral to initiation of treatment. Twelve major processes in referral, review, diagnostics, assessment, triage and consult were redesigned. TOH now provides a diagnosis to 80% of referrals within the provincial target of 28 days and leads all other jurisdictions in Ontario in this metric by a wide margin. The median patient journey from referral to initial treatment decreased 48% from 92 to 47 days. In 2016 this work was recognized by a provincial cancer agency with a quality award.
Conclusion:
A learning health system has significantly reduced the time from referral with suspicion of lung cancer to diagnosis to treatment. Achievements require a multi-disciplinary approach with a regional perspective. Patient and family advocates have an important voice in re-designing health care systems.
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OA 14 - New Paradigms in Clinical Trials (ID 681)
- Event: WCLC 2017
- Type: Oral
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:Alex Adjei, Eun Kyung Cho
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 311 + 312
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OA 14.02 - Rethinking Progression-Free Survival (PFS) as a Clinical Trials Surrogate for Overall Survival (OS) (ID 10276)
11:10 - 11:20 | Presenting Author(s): David James Stewart
- Abstract
- Presentation
Background:
►►OS assessment requires high follow-up times and patient numbers and is impacted by crossover (CO). OS hazard ratios (HRs) are generally inferior to PS HRs due to impact of post-progression survival (PPS) and CO. Some authors propose that absolute OS gains (ΔOS) should be similar to those in PFS (ΔPFS). Hence, ΔPFS might be a useful OS surrogate (Clin Cancer Res 2013;19:2646; Ann Oncol 2016;27:373).
Method:
To assess this further, we reviewed Journal of Clinical Oncology and New England Journal of Medicine 01/01/2012-06/12/2017 for randomized drug trials in incurable solid tumors. We extracted data for PFS and OS medians and HRs, calculated ΔPFS and ΔOS (experimental medians minus control medians), and did paired comparisons between 2-6 different arms in each study (245 comparisons across 201 trials).
Result:
Mean ΔOS across studies (1.03 months) was similar to mean ΔPFS (1.06 months) (n=201 evaluable, p=0.88). ΔOS correlated with ΔPFS (r=0.50, p<0.0001). With CO in <20% of patients or unstated %CO (n=144), mean ΔOS and ΔPFS were 0.93 and 0.92 months, respectively. With CO in >20% of patients (n=57), mean ΔOS and ΔPFS were 1.29 and 1.41 months, while with CO>50% (n=20), they were 1.4 and 1.9 months. OS HRs (mean=0.92) were inferior to PFS HRs (mean=0.82, n=196, p<0.0001), although OS and PFS HRs correlated with each other (r=0.64, p<0.0001). With CO<20% or unstated (n=135), mean OS and PFS HRs were 0.93 and 0.83, while with CO>20% (n=61), they were 0.90 and 0.80, and with CO>50% (n=20), they were 0.94 and 0.71.
Conclusion:
OS HRs were inferior to PFS HRs, probably due to PPS, competing causes of death and CO. The better mean gains and HRs in high vs low CO trials may be due to more frequently allowing CO in trials with more effective therapies. This increases risk of false-negative OS results with effective therapies if CO is permitted, but it is potentially unethical to withhold CO of effective therapies. With PFS, clinically insignificant gains may be statistically significant. Since ΔOS and ΔPFS are similar, an alternate approach would be a primary study outcome requiring PFS HR to be statistically significant and ΔPFS 95% CIs in a range considered clinically relevant for OS gains. To better understand the limitations of this approach, we are analyzing examples with minimal OS gains despite ΔPFS>2 months and examples of ΔOS>2 months but no gain in PFS, and have formulated a potential biological/statistical explanation for the latter.
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