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M. Forster
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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)
12:05 - 12:15 | Author(s): M. Forster
- 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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P1.03 - Poster Session with Presenters Present (ID 455)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.03-010 - Characteristics of Lung Cancer Patients Diagnosed Following Emergency Admission (ID 5091)
14:30 - 14:30 | Author(s): M. Forster
- Abstract
Background:
The proportion of patients with cancers diagnosed via the emergency route and their demographic characteristics vary according to tumour type[1]. Patients with lung cancers diagnosed as emergency presentations suffer worse outcomes[2]. The aim of this observational study was to determine the characteristics of a sample of patients with new lung cancers presenting through the emergency route.
Methods:
Clinical and demographic patient data were extracted from the London Cancer Registry. Data relating to emergency presentations of lung cancer were collected prospectively between January and August 2013 from nine acute trusts across northeast and central London and west Essex. Clinical and demographic characteristics were collated. The total number of emergency presentations were compared to the total numbers of lung cancers diagnosed within the same region over the corresponding time frame from the National Lung Cancer Audit data (NLCA).
Results:
Figure 1From the NLCA, there were an estimated 964 lung cancers recorded within the London cancer region during the study period. Of these, 310 (32%) lung cancers were recorded in the London Cancer registry as having presented via the emergency route. The median age of these patients was 73. The majority of patients were white and from areas of increased social deprivation. The proportion of patients presenting with stage IV disease was 67%, while 58% had a performance status of 0-2. The most common presenting symptoms were respiratory. 95% of patients were treated with palliative rather than curative intent.
Conclusion:
Approximately one third of new lung cancers within London Cancer are diagnosed following emergency admission. The next phase of work includes incorporating results from the London Cancer Alliance to provide pan-London data and to develop tools in primary care to identify these patients prior to emergency admission.
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-028 - A Phase 2 Study of Prexasertib in Patients with Extensive Stage Small Cell Lung Cancer (ID 4176)
14:30 - 14:30 | Author(s): M. Forster
- Abstract
Background:
Checkpoint kinase 1 (CHK1), plays a role in cell cycle regulation and DNA damage repair. Prexasertib monomesylate monohydrate (prexasertib, or LY2606368) inhibits CHK1 and induces replication catastrophe. As monotherapy, it demonstrated an acceptable safety profile and preliminary evidence of efficacy in Phase 1. Replication stress, together with defects in cell cycle checkpoints and/or DNA damage repair pathways may sensitize tumors to CHK1 inhibitors. Small cell lung cancer (SCLC) tumors have high levels of replication stress through mechanisms such as MYC amplification and high rates of TP53 mutations, RB1 loss, and genomic rearrangements. Preclinical models of SCLC demonstrate sensitivity to prexasertib monotherapy. As a result, prexasertib is an attractive agent to evaluate in patients with SCLC.
Methods:
This is a parallel cohort, non-randomized, open-label, multicenter Phase 2 study (NCT02735980) in patients with extensive disease (ED)-SCLC. Cohort 1 includes patients with platinum-sensitive disease (objective response to prior platinum-based therapy with subsequent progression ≥90 days after last platinum dose). Cohort 2 includes patients with platinum‑resistant/refractory disease (patients who either did not have an objective response to prior platinum-based therapy or had progression <90 days after last platinum dose). The primary objective is best overall response rate per cohort as determined per RECIST v1.1. Secondary objectives include evaluation of safety/toxicity, pharmacokinetics, and efficacy measures; which include overall survival, progression-free survival, duration of response, and disease control rate. Safety will be assessed by collecting and grading AEs as per CTCAE v4.0. Exploratory biomarkers associated with efficacy and safety of prexasertib may also be assessed. Key inclusion criteria include: patients ≥18 years having histologic or cytologic diagnosis of ED‑SCLC who received prior platinum therapy; ≥1 measurable lesion per RECIST v1.1; ECOG performance status of 0 or 1; discontinued prior therapies ≥14 days before first dose of prexasertib. Key exclusion criteria include: received ≥2 prior therapies for ED-SCLC; symptomatic CNS metastases, prior treatment with CHK1 inhibitor; or serious cardiac conditions. Prexasertib will be administered as intravenous infusion every 14 days. Disease will be assessed by radiographic imaging every 6 weeks. Approximately 116 patients (58 per cohort) are planned for enrollment in 10 countries (>60 sites). An interim futility analysis will be conducted in each cohort after 29 patients have completed cycle 3 and, if required, the response is confirmed. Enrollment began in May 2016.
Results:
Section not applicable.
Conclusion:
Section not applicable.
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P3.06 - Poster Session with Presenters Present (ID 492)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Trial Design/Statistics
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.06-002 - ATLANTIS Trial: Phase III Study of PM01183/Doxorubicin vs. CAV or Topotecan in SCLC after One Platinum-Containing Line (ID 5877)
14:30 - 14:30 | Author(s): M. Forster
- Abstract
Background:
PM01183 (lurbinectedin) is a new anticancer drug that blocks trans-activated transcription, induces DNA double-strand breaks and modulates the tumor microenvironment. Synergism in combination with doxorubicin with compelling overall response rates (~67%, including approximately 10% complete responses) was reported in a phase I expansion cohort in 21 second-line SCLC patients (pts) (ASCO 2015, abstract 7509). The most common toxicity observed was hematologic.
Methods:
Multinational, multicenter (>150 sites), open-label, randomized, phase III study of PM01183/doxorubicin vs. a control arm with investigator choice of either standard CAV or topotecan (1.5 mg/m[2], D1-5 q3wk). A total of 600 pts will be randomized (1:1) and stratified according to ECOG performance status (PS), chemotherapy-free interval (CTFI), known CNS involvement, prior PD-1/PD-L1 based immunotherapy and potential investigator’s control preference. Patients with clinical benefit after 10 cycles of doxorubicin containing-combination will continue on single agent PM01183 or CV, until PD or unacceptable toxicity. Interim safety analysis will be performed after 150 pts by an independent data monitoring committee. The most relevant inclusion criteria are: pts ≥18 years old; confirmed diagnosis of SCLC (small-cell carcinomas from unknown site are eligible provided ≥50% Ki-67 expression). One prior platinum containing regimen is mandatory (additional immunotherapy is allowed provided that it was not given in combination with CT); PS: 0-2 and adequate major organ function, including normal LVEF ≥50% at baseline. Pts are excluded if pre-treated with PM01183, doxorubicin or topotecan; symptomatic or steroid requiring CNS involvement or any serious medical condition that might preclude safe compliance with study treatment. The primary objective is to determine a difference in progression-free survival by an independent review committee. Secondary endpoints are overall survival, survival rates at 12/18/24 months, antitumor response (RECIST v1.1), duration of response, QoL, safety, subgroup analyses and pharmacokinetics (PK) of PM01183/doxorubicin arm. First patient is planned in JUL2016. Enrollment is expected to be completed by 4Q17.
Results:
Section not applicable
Conclusion:
Section not applicable
