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K. Takeda
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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
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MINI03.06 - Phase II Studies of Nivolumab in Patients with Advanced Squamous (SQ) or Non-Squamous (NSQ) Non-Small-Cell Lung Cancer (NSCLC) (ID 1329)
16:45 - 18:15 | Author(s): K. Takeda
- Abstract
- Presentation
Background:
Nivolumab (anti-PD-1, ONO-4538, BMS-936558), a fully human IgG4, PD-1 immune-checkpoint inhibitor antibody, has shown durable clinical activity in previous[MS誠1] phase I and II trials in several tumor types. In March 2015, U.S. Food and Drug Administration (FDA) has approved Nivolumab for the treatment of patients with metastatic squamous (SQ) non-small-cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Here, we report the results of two phase II studies to evaluate the efficacy and safety of nivolumab in previously treated advanced SQ (JapicCTI-No.132072) and NSQ (JapicCTI-No.132073) NSCLC pts.
Methods:
Both studies required pts aged ≥ 20 years with an ECOG performance status of 0 or 1, stage IIIB/IV, or recurrent NSCLC and at least one prior chemotherapy including platinum containing regimen. Pts received nivolumab 3 mg/kg IV Q2W until disease progression or unacceptable toxicity. The primary endpoint in both studies was the objective response rate (ORR) (RECIST v1.1). Planned sample size was 30 pts for SQ and 67 pts for NSQ, respectively (P~0~[MS誠1] =0.09 &[MS誠2] P~1~=0.26, P~0~=0.09 & P~1~=0.20 ; α=0.025 (one-side), 1-β=0.8).
Results:
From April 2013 to April 2014, a total of 111 NSCLC pts were enrolled in both studies (35 pts with SQ, 76 pts with NSQ, male/female: 81/30; PS 0/1: 46/55; aged 31 to 84 [median: 65.0] years; Stage IIIB/Stage IV/recurrence: 6/86/19). Objective response rates (ORRs) were 25.7% (9/35) [95% CI: 14.2, 42.1] in SQ and 19.7% (15/76) [95% CI: 12.3, 30.0] in NSQ, respectively. Complete Response was observed in 2.6% with NSQ. Median progression-free survival (mPFS) was 4.2 months (95% CI: 1.4, 7.1) for SQ and 2.8 months (95% CI: 1.4, 3.4) for NSQ, respectively. Median follow-up periods were 10.4 months and 8.4 months, respectively. Median duration of response was not reached in each study. Of 9 SQ pts and 15 NSQ pts who responded to nivolumab, durable and ongoing response was observed in 77.8% (7/9) and 80.0% (12/15), respectively. Median overall survival was not reached in either study. All Grade drug-related adverse events across both studies were 79.3% (88/111) and Grade 3-4 drug-related adverse events (G3-4 AEs) were observed in 16.2% (18/111) pts. Most common G3-4 AEs were lymphocyte count decreased 3.6% (4/111), hyponatremia 1.8% (2/111), interstitial lung disease 1.8% (2/111), pleural effusion 1.8% (2/111). Any grade of interstitial lung disease was observed in 4.5% (5/111) pts. No grade 5 AEs were observed.
Conclusion:
In these studies, nivolumab showed encouraging clinical efficacy in both SQ and NSQ NSCLC with a manageable safety profile.
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MINI 15 - Chemotherapy Developments for Lung Cancer (ID 128)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:L. Crinò, C.P. Belani
- Coordinates: 9/08/2015, 16:45 - 18:15, Mile High Ballroom 1a-1f
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MINI15.08 - A Phase II Study of Pemetrexed plus Carboplatin Followed by Maintenance Pemetrexed in Elderly Patients with Advanced Non-Squamous NSCLC (ID 2453)
16:45 - 18:15 | Author(s): K. Takeda
- Abstract
- Presentation
Background:
Non-small-cell lung cancer (NSCLC) accounts for >80% of all lung cancers, and the risk of lung cancer clearly increases with advancing age. Because of the progressive aging of population, the number of elderly patients with NSCLC is increasing and the desease is becoming an increasing public health problem worldwide. We previously reported a phase I study that recommended a dose of carboplatin (Cb, area under the curve = 5) plus pemetrexed (PEM, 500 mg/m[2]) for elderly (≥75-years-old) patients with non-squamous NSCLC. Furthermore, PEM maintenance therapy, following the combination therapy, was also found to be well tolerated. Therefore, we conducted a multicenter phase II trial to evaluated the efficacy and safety of Cb (area under the curve = 5) plus PEM (500 mg/m[2]) followed by maintenance PEM for elderly (≥75-years-old) patients with non-squamous NSCLC.
Methods:
Treated patients received 4 courses of Cb plus PEM, followed by maintenance PEM, without showing disease progression or severe toxicities. The primary endpoint was the 1-year overall survival (OS) rate, and the secondary endpoints were OS, progression free survival (PFS), response rate (RR), and safety.
Results:
Thirty four patients were enrolled between June 2012 and May 2013. All patients had an ECOG performance status 0 or 1, and adenocarcinoma. The median patient age was 77 years (75-84 years). Twenty four patients were male and ten patients were female. Three patients harbored activating epidermal growth factor recepter mutation (exon19 or 21). The median observation time was 22.7 months. In clinical outcome, the overall RR was 41.2%, and the disease control rate was 85.3%. No patient showed a complete response, 14 showed partial responses, 15 showed stable disease, 4 showed disease progression, and 1 was not evaluated. The maintenance therapy rate was 58.8%. The median PFS for all patients was 5.7 months (95% confidence interval, 3.3–8.5 months), whereas the median OS was 20.5 months (95% confidence interval, 7.8–25.4 months). The 1-year OS rate was 58.0%. In adverse events (total phase of this study), hematological adverse events ≥grade 3 were leucopenia (in 23.5% of patients), neutropenia (55.9%), anemia (35.3%), and thrombocytopenia (20.6%), and major non-hematological adverse events ≥grade 3 were febrile neutropenia (in 8.8% of patients), increased levels of aminotransferase (5.9%), infection (23.5%), and anorexia/fatigue (5.9%). There was 1 treatment-related death due to interstitial lung disease.
Conclusion:
The combination of Cb plus PEM followed by maintenance PEM was effective and reasonably well tolerated in chemotherapy-naïve elderly (≥75-years-old) patients with non-squamous NSCLC. This data was promising and valuable to conduct the phase III study compared with docetaxel (DOC) monotherapy in the first-line setting. Now, the phase III trial compared Cb plus PEM followed by maintenance PEM with DOC for chemotherapy-naïve elderly (≥75-years-old) patients with non-squamous NSCLC (JCOG1210/WJOG7813L: UMIN000011460) is ongoing and the result is warranted. Clinical trial information: UMIN000004810
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-020 - Updated Data from JP28927 Study of Alectinib in ALK+ NSCLC Patients with or without History of ALK Inhibitor Treatment (ID 346)
09:30 - 17:00 | Author(s): K. Takeda
- Abstract
Background:
Alectinib, a next generation ALK inhibitor, was granted approval in Japan 2014, since it showed good efficacy and tolerability in ALK+ NSCLC patients without previous ALK inhibitor treatment in Phase I/II study (AF-001JP). We also reported its promising response and good tolerability for crizotinib pre-treated patients in JP28927 study (ESMO 2014). This report describes the update of efficacy and safety result in JP28927 study.
Methods:
Patients (with/without prior ALK inhibitor treatment) who had ALK+ NSCLC were enrolled in JP28927. Patients received alectinib (300mg) twice daily; treatment was continued until the investigator determined lack of clinical benefit.
Results:
Thirty-five patients were enrolled into JP28927 study. Median follow-up duration was 400 days (35-457 days). The median progression free survival (PFS) of 35 patients was 13.9 months (95%CI: 11.1- NR). Among 30 patients with the target lesions at base line, the overall response rate (ORR) was 70% (95%CI: 50.6-85.3) with rapid response (the median time to response was 1.2 months [95%CI: 1.1-2.1]). Twenty-three out of 35 patients had been confirmed the progressive disease with crizotinib treatment. Their median PFS was 12.9 months (95%CI: 3.9-NR). Twenty out of 23 patients had the target lesions at base line. ORR was 65% (95%CI: 40.8-84.6) and the median time to response was 1.2 months (95%CI: 1.1-1.3). The treatment-related adverse events (AEs) observed in more than 10% of the patients were constipation (31.4%), dysgeusia (25.7%), WBC count decreased (22.9%), neutrophil count decreased (22.9%), vomiting (14.3%), rash (14.3%), blood bilirubin increased (14.3%) and AST increase (14.3%). Treatment-related Grade 3 AEs, i.e. pulmonary thrombosis, lymphocyte count decrease, hypophosphatemia, were observed in 3 patients. No treatment-related Grade 4 or 5 AEs were observed.
Conclusion:
The updated results in JP28927 study once again endorsed our previous reports which had indicated alectinib’s promising response even for ALK+NSCLC patients who failed to crizotinib treatment.
