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D. Waterhouse
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-051 - Nivolumab Versus Chemotherapy as Post-Platinum Therapy for Advanced Non-Small Cell Lung Cancer in a Real-world Setting (ID 8483)
09:30 - 16:00 | Author(s): D. Waterhouse
- Abstract
Background:
Nivolumab, an immune checkpoint inhibitor, is approved for advanced non-small cell lung cancer (NSCLC) after platinum-based chemotherapy, based on results of 2 pivotal studies (CheckMate 017 and 057). This prospective observational study (CA209-118) compared outcomes with nivolumab versus chemotherapy as post-platinum therapy for NSCLC in a real-world community setting.
Method:
This analysis, as of May 16, 2017, included patients with advanced NSCLC who completed an initial course of platinum-based chemotherapy and started subsequent treatment prior to November 16, 2016, with a minimum of 6 months of potential follow-up. Patients receiving experimental therapy, immunotherapy other than nivolumab, or tyrosine kinase inhibitors for EGFR/ALK-mutated NSCLC were excluded. Patients in this non-randomized study were grouped by receipt of nivolumab or chemotherapy as first post-platinum therapy and followed until death, study discontinuation, or initiation of subsequent immunotherapy. Unadjusted and adjusted survival analyses were conducted. For adjusted analysis, multivariate regression was performed that included age, ECOG performance status score, time since stage IV diagnosis, smoking status, and squamous histology as covariates.
Result:
Of 383 eligible patients, 161 received post-platinum nivolumab and 222 received post-platinum chemotherapy, including 158 who received a regimen recommended by the National Comprehensive Cancer Network (docetaxel, pemetrexed, gemcitabine, ramucirumab + docetaxel, or erlotinib) and 40 who received a second platinum-based regimen. Baseline characteristics were well balanced between treatment groups, except that the percentage of men was higher in the nivolumab versus chemotherapy group (59% vs 49%). Mean age was 66 years, and 79% of patients had non-squamous histology. In all, 65% of patients in the nivolumab group and 69% in the chemotherapy group started post-initial platinum therapy ≤1 year after stage IV diagnosis. Median survival from the start of post-initial platinum therapy was 11.5 months (95% confidence interval [CI]: 7.9, not reached) in the nivolumab group and 8.3 months (95% CI: 6.1, 11.0) in the chemotherapy group. Unadjusted survival analyses showed a reduction in mortality risk of 20% with nivolumab versus chemotherapy (hazard ratio = 0.80; 95% CI: 0.59, 1.08); adjusted survival analyses yielded comparable results. In the nivolumab and chemotherapy groups, respectively, 9% and 18% of patients discontinued due to adverse effects; 41% and 49% discontinued due to death or disease progression.
Conclusion:
The results of this early survival analysis from a prospective study in a real-world community setting were similar to those seen in randomized trials, further supporting the benefit of nivolumab over chemotherapy in previously treated advanced NSCLC.
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P1.03 - Chemotherapy/Targeted Therapy (ID 689)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.03-026 - Interim Results of a Phase I Study of Nivolumab plus Nab-Paclitaxel/Carboplatin in Patients with NSCLC (ID 8478)
09:30 - 16:00 | Author(s): D. Waterhouse
- Abstract
Background:
Chemotherapy, including taxanes, may augment the effects of immune checkpoint inhibitors through tumor cell lysis and subsequent antigen release. This phase I trial is evaluating safety and efficacy of nivolumab plus nab-paclitaxel in NSCLC (+ carboplatin), pancreatic cancer (± gemcitabine), and metastatic breast cancer. Interim results for Arm C, in which patients with NSCLC were treated with nivolumab starting in cycle 1, are presented.
Method:
Potential dose-limiting toxicities (DLTs) were evaluated in Part 1 before Part 2 expansion. Chemotherapy-naive patients with histologically/cytologically confirmed stage IIIB/IV NSCLC received 4 cycles of nab-paclitaxel 100 mg/m[2] days 1, 8, 15 plus carboplatin AUC 6 day 1 plus nivolumab 5 mg/kg day 15 of each 21-day cycle. In cycles ≥ 5, single-agent nivolumab was continued as maintenance therapy. Primary endpoints are number of patients with DLTs (Part 1) and percentage of patients with grade 3/4 treatment-emergent adverse events (TEAEs) or treatment discontinuation due to TEAEs (Parts 1/2). DLT-evaluable patients were those who received ≥ 2 complete nivolumab cycles and remained on study for 14 days after the last nivolumab dose in cycle 2, received ≥ 1 nivolumab dose and discontinued due to DLT before completing 2 nivolumab cycles, or experienced an equivocal DLT after ≥ 1 nivolumab dose. Secondary endpoints included PFS, DCR, ORR, DOR (all by RECIST v1.1), OS, and safety.
Result:
All patients (N = 22) received nab-paclitaxel/carboplatin; results for those who received nab-paclitaxel/carboplatin plus nivolumab (n = 20) are presented. The median age was 65.5 years (55% ≥ 65 years), 70% had ECOG PS 1, 75% were female, and 80% were white. More patients had adenocarcinoma (50%) than squamous cell carcinoma (35%; adenosquamous carcinoma, atypical, and data pending, 5% each). No DLTs were reported among 6 DLT-evaluable patients (Part 1). The most common grade 3/4 TEAEs were neutropenia (45%) and anemia (40%). No grade 3/4 colitis or pneumonitis was reported. Best ORR was 50% (1 CR [5%] and 9 PRs [45%]; 10 patients [50%] had SD); ORR was 43% (3 PRs among 7 patients) and 54% (1 CR and 6 PRs among 13 patients) in those with squamous and nonsquamous histologies, respectively. Median PFS was 10.5 months (95% CI, 4.9-18.1 months); 10.5 and 10.2 months for those with squamous and nonsquamous histologies, respectively.
Conclusion:
These results suggest that nab-paclitaxel/carboplatin plus nivolumab is tolerable for patients with NSCLC. Preliminary efficacy findings indicate promising antitumor activity across histologies. (NCT02309177)
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P3.07 - Immunology and Immunotherapy (ID 723)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.07-012 - Nivolumab Versus Docetaxel in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer and Liver Metastases (ID 8484)
09:30 - 16:00 | Author(s): D. Waterhouse
- Abstract
Background:
Patients with non-small cell lung cancer (NSCLC) who have metastasis to the liver have poor prognosis. The phase 3 trials CheckMate 017 and 057 demonstrated improved overall survival (OS) and a favorable safety profile with nivolumab, an anti-programmed death-1 antibody, versus docetaxel in patients with previously treated advanced squamous and non-squamous NSCLC, respectively. A prior subgroup analysis from these trials evaluated and demonstrated efficacy and safety with nivolumab in patients with asymptomatic central nervous system metastases (Goldman J. ASCO 2016). Here we report subgroup analyses from these trials of patients with baseline liver metastases.
Method:
In both trials, patients were randomized 1:1 to nivolumab 3 mg/kg every 2 weeks or docetaxel 75 mg/m[2] every 3 weeks until progression or discontinuation. The primary endpoint of each study was OS. Patients from CheckMate 017 and 057 with baseline liver metastases reported as either target or non-target lesions were identified and pooled across studies by treatment.
Result:
Baseline characteristics were generally similar between patients with liver metastases randomized to nivolumab (n=99) and docetaxel (n=94). In the nivolumab group, 26% of patients had squamous and 74% had non-squamous NSCLC; in the docetaxel group, 36% had squamous and 64% had non-squamous NSCLC. The minimum follow-up was 24.2 months (Feb 2016 database locks). Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio [HR]=0.68; 95% confidence interval [CI]: 0.50, 0.91), similar to findings from the ITT group (HR=0.72; 95% CI: 0.62, 0.84). Median OS in patients with liver metastases was 6.83 months with nivolumab versus 5.93 months with docetaxel, both of which were lower than those observed in the overall pooled intent-to-treat (ITT) population (11.14 months vs 8.11 months). Two-year OS rates were 18% with nivolumab versus 6% with docetaxel in patients with liver metastases. Rates of grade 3−4 treatment-related adverse events in patients with liver metastases were lower with nivolumab compared with docetaxel (7% vs 53%), and similar to those in the ITT population (10% vs 55%).
Conclusion:
The lower median OS observed in this subgroup of patients with previously treated advanced NSCLC and baseline liver metastases corroborates previous findings that metastasis to the liver is an unfavorable prognostic factor. However, nivolumab demonstrated sustained OS benefit versus docetaxel in these patients, similar to the ITT population. The safety profile of nivolumab was favorable versus docetaxel in this subgroup, with no new safety concerns identified.
