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W. Su
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OA03 - Immunotherapy Checkpoint Inhibitors in Advanced NSCLC (ID 367)
- Event: WCLC 2016
- Type: Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
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OA03.07 - KEYNOTE-010: Durable Clinical Benefit in Patients with Previously Treated, PD-L1-Expressing NSCLC Who Completed Pembrolizumab (ID 6769)
11:00 - 12:30 | Author(s): W. Su
- Abstract
- Presentation
Background:
Checkpoint inhibitors such as the anti–PD-1 monoclonal antibody pembrolizumab have demonstrated antitumor activity and a manageable safety profile in several advanced malignancies. Although checkpoint inhibitors are rapidly becoming a standard-of-care therapy in multiple tumor types, the optimal treatment duration has not been established. We assessed outcomes in patients who completed the maximum 24 months of pembrolizumab in the phase 3 KEYNOTE-010 study (NCT01905657), in which pembrolizumab provided superior OS over docetaxel in patients with previously treated, PD-L1–expressing advanced NSCLC.
Methods:
1034 patients with advanced NSCLC that progressed after ≥2 cycles of platinum-based chemotherapy (and an appropriate therapy for targetable EGFR and ALK aberrations if present) and had a PD-L1 tumor proportion score ≥1% were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg Q3W or to docetaxel 75 mg/m[2] until disease progression, intolerable toxicity, or physician or patient decision; the maximum duration of pembrolizumab was 24 months of uninterrupted treatment or 35 cycles, whichever was later. Response was assessed per RECIST v1.1 by independent central review every 9 weeks. After completion of 24 months/35 cycles, patients continued to undergo imaging every 9 weeks; patients with subsequent disease progression were eligible for a second treatment course if they did not receive other anticancer therapy after stopping pembrolizumab.
Results:
In the overall population, median OS was longer (10.5 months for pembrolizumab Q2W, 13.4 months for pembrolizumab Q3W, and 8.6 months for docetaxel) and 24-month OS rates were higher (30.1%, 37.5%, and 14.5%, respectively) with pembrolizumab compared with docetaxel. Of the 691 patients allocated to pembrolizumab, 47 patients received 35 cycles of pembrolizumab and were included in this analysis. As of the September 30, 2016 data cutoff date, all patients had completed all 35 cycles of treatment, but one withdrew from the study treatment after completing 35 cycles. Best overall response (ORR) among these 47 patients was complete response (CR) in 3 (6%) patients and partial response (PR) in 39 (83%) patients, for an ORR of 89%; 5 (11%) patients experienced stable disease (SD). Two of these patients experienced disease progression since stopping pembrolizumab and two of these patients resumed pembrolizumab therapy. As of the cutoff date, none of the 47 patients had died.
Conclusion:
With long-term follow-up, the OS benefit has been maintained and pembrolizumab continues to demonstrate superiority over docetaxel. Pembrolizumab provides durable clinical benefit with few patients progressing after completing two years of therapy.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-005 - Phase Ib Trial of Afatinib and BI 836845 in Advanced NSCLC: Dose Escalation and Safety Results (ID 4719)
14:30 - 15:45 | Author(s): W. Su
- Abstract
Background:
Insulin-like growth factor (IGF) signaling is implicated in acquired resistance to EGFR TKIs in NSCLC. BI 836845 is an IGF ligand-neutralizing antibody that binds to IGF-1 and IGF-2, and inhibits their growth-promoting activities. This Phase Ib trial evaluates BI 836845 in combination with afatinib in patients with NSCLC progressing following prior treatment with EGFR TKIs or platinum-based chemotherapy (NCT02191891).
Methods:
The trial consists of two sequential parts: a dose confirmation part (Part A, reported here) and an expansion part (Part B). In Part A, eligible patients were aged ≥18 years with advanced and/or metastatic NSCLC progressing on EGFR TKIs (patients with EGFR mutations) or platinum-based chemotherapy. Patients receiving prior afatinib therapy below the assigned dose level or <30mg/day, or with progression on an insufficient dose of EGFR TKI prior to the study, were excluded. Part A used a 3+3 dose-escalation design with a starting dose of BI 836845 1,000mg/week (1-hour intravenous infusion) plus oral afatinib 30mg/day, in 4-week cycles. Primary endpoints were the maximum tolerated dose (MTD) of BI 836845 in combination with afatinib, and the occurrence of dose-limiting toxicities (DLTs) during Cycle 1.
Results:
At data cut-off (18 April 2016), 16 patients were treated (BI 836845 1,000mg/afatinib 30mg [n=4]; BI 836845 1,000mg/afatinib 40mg [n=12]). Median age (range) was 60 (48–77) years. Fourteen (88%) patients had activating EGFR mutations. Nine (56%) patients discontinued treatment, mostly due to progressive disease (one patient discontinued BI 836845 for other reasons); seven patients remain on treatment. During Cycle 1, 0/3 patients (afatinib 30mg) and 0/12 patients (afatinib 40mg) had a DLT (one patient [afatinib 30mg] was replaced during Cycle 1 due to a non-DLT adverse event [AE]). Therefore, the MTD and recommended Phase II dose (RP2D) was determined to be BI 836845 1,000mg/week in combination with afatinib 40mg/day. All patients experienced at least one drug-related AE; the most common were diarrhea (n=12; 75%), paronychia (n=11; 69%) and rash (n=10; 63%). Drug-related AEs were mostly grade 1/2 (one patient [afatinib 30mg] had grade 3 stomatitis). No drug-related AEs led to discontinuation and no dose reductions were required for BI 836845 or afatinib.
Conclusion:
The MTD and RP2D of BI 836845 was determined as 1000mg/week in combination with afatinib 40mg/day in patients who have failed prior EGFR TKIs or chemotherapy. This combination demonstrated a clinically manageable safety profile, consisting of AEs commonly associated with afatinib. The expansion part (Part B) is ongoing.
