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12098 Background: In a randomized, double-blind, placebo-controlled trial (J-FORCE), we previously reported the efficacy of olanzapine (OLZ) 5 mg plus triplet antiemetic therapy for cisplatin (CDDP)-based chemotherapy-induced nausea and vomiting (CINV) in the delayed phase (24–120 h after CDDP treatment). Here, we report the results of a pre-planned subgroup analysis of this trial (in which risk factors were used as the allocation factors). This analysis was designed to determine which patients benefit more from OLZ. Methods: Subgroup analysis was performed on complete response (CR: no emesis and no rescue medication) in the acute (within 24 h of CDDP treatment) and delayed phase and time to treatment failure (TTF: time from CDDP treatment to the first vomiting or use of rescue medication). Data from 705 patients in the efficacy analysis population (354 in the OLZ group and 351 in the placebo (PLA) group) were analyzed by sex (male/female), age (≥55 years/ < 55 years), and CDDP dose (≥70 mg/m2/ < 70 mg/m2). For CR, we calculated point estimates of differences between groups and 95% confidence intervals and performed a Mantel-Haenszel test. We used the Kaplan-Meier method for the analysis of TTF, and comparisons between groups were made using a log-rank test. Results: Delayed CR (OLZ versus PLA) and risk difference (RD) of delayed CR following OLZ treatment were significantly greater than following PLA in the following subgroups: male (83.1% versus 70.5%, RD 12.6%, p = 0.001), female (70.9% versus 56.4%, RD 14.5%, p = 0.021), age ≥55 years (78.7% versus 67.6%, RD 11.1%, p = 0.003), age < 55 years (81.0% versus 57.4%, RD 23.6%, p = 0.005), and CDDP ≥70 mg/m2 (78.8% versus 65.3%, RD 13.5%, p < 0.001). TTF of all subgroups (male/female, ≥55 years/ < 55 years, and ≥70 mg/m2/ < 70 mg/m2) was significantly longer in the OLZ group than in the PLA group (HR 0.493, p < 0.001; HR 0.612, p = 0.022; HR 0.586, p < 0.001; HR 0.401, p = 0.005; HR 0.546, p < 0.001; HR 0.543, p = 0.031, respectively). Conclusions: Our results suggest a benefit of OLZ 5 mg plus triplet therapy regardless of risk factors for CDDP-based CINV. Clinical trial information: UMIN000024676. [Table: see text]

9038 Background: Previous clinical trials demonstrated that alectinib (ALEC) had a longer time-to-progression than crizotinib (CRZ) in 1st-line settings. Information on long-term overall survival (OS), however, is still limited with a few studies having reported that the sequential strategy of “CRZ followed by other ALK-inhibitor” can provide extended OS. In Japan, ALEC was approved for a 1st-line setting earlier than in other countries. Methods: We reviewed the clinical data of ALK-rearranged NSCLC patients who received CRZ or ALEC between May 2012 and Dec 2016. Patients were divided into two groups according to the first-administered ALK inhibitor, the CRZ or ALEC group. In order to evaluate the efficacy of the sequential strategy of “CRZ followed by ALEC”, the combined time to treatment failure (TTF) was calculated in the CRZ group as defined by the sum of the “TTF of CRZ” plus the “TTF of ALEC” if patients were treated with ALEC followed by CRZ. In the ALEC group, the “TTF of ALEC” was calculated. The primary endpoint is the comparison between the combined TTF in the CRZ group with the TTF in the ALEC group. Results: Of 864 patients enrolled from 61 institutions, 840 patients were analyzed. Median age was 61 (range, 20-94); 56% were female; and 95% had adenocarcinoma. There were 535/305 patients in the CRZ/ALEC group. In the CRZ group, 282 patients received ALEC after CRZ failure. The combined TTF in the CRZ group was significantly longer than TTF in the ALEC group; median, 34.4 vs 27.2 months (mo); hazard ratio (HR), 0.709 [95%CI;0.559- 0.899]; P= 0.0044. However, there was no significant difference in OS between the patients who received ALEC after CRZ in the CRZ group and the patients in the ALEC group; median, 88.4 months vs. not reached; HR 1.048 [95%CI;0.758-1.451]; P= 0.7770. In the whole population, the CRZ group had a significantly shorter OS than the ALEC group; median, 53.6 mo vs not reached HR, 1.821 [95%CI;1.372-2.415]; P< 0.0001. Conclusions: The combined TTF in the CRZ group was significantly longer than TTF in the ALEC group, however, OS benefit of sequential therapy of CRZ followed by ALEC was not shown. Clinical trial information: UMIN000028605.

8529 Background: Chemoradiation regimens of greater efficacy are needed for patients with locally advanced non–small cell lung cancer (NSCLC). Methods: Patients between 20 and 74 years of age with unresectable NSCLC of stage IIIA or IIIB and a performance status of 0 or 1 were eligible for the study. In the phase II part of the study, patients received weekly nab-paclitaxel at 50 mg/m2 together with weekly carboplatin at an area under the curve (AUC) of 2 mg mL–1 min and concurrent radiotherapy with 60 Gy in 30 fractions. This concurrent phase was followed by a consolidation phase consisting of two 3-week cycles of nab-paclitaxel plus carboplatin. The primary end point of the phase II part of the study was progression-free survival (PFS). Results: Between October 2014 and November 2016, 58 patients were enrolled at 14 institutions in Japan, with 56 of these individuals being evaluable for treatment efficacy and safety. At the median follow-up time of 26.0 months (range, 4.0 to 49.6 months), the median overall survival (OS) was not reached (95% confidence interval [CI], 25.3 months to not reached) and the 2-year OS rate was 66.1% (95% CI, 52.1% to 76.8 %). The median PFS was 11.8 months (60% CI, 10.6 to 16.8 months; 95% CI, 8.2 to 21.0 months). The overall response rate was 76.8% (95% CI, 64.2% to 85.9%), and the disease control rate was 94.6% (95% CI, 85.4% to 98.2%). Subgroup analysis according to histology or age revealed no significant differences in median PFS or OS. Common toxicities of grade 3 or 4 in the concurrent phase included leukopenia (60.7%) and neutropenia (28.6%). Pneumonitis of grade 3 was observed in two patients during the study period. No treatment-related deaths occurred. Conclusions: Our results reveal encouraging feasibility and activity for concurrent chemoradiation with nab-paclitaxel at 50 mg/m2 and carboplatin at an AUC of 2 mg mL–1 min in patients with locally advanced NSCLC. Clinical trial information: UMIN000012719.

TPS9125 Background: First-line treatment of non–small cell lung cancer (NSCLC) has undergone a paradigm shift to platinum combination therapy together with an immune-checkpoint inhibitor. Bevacizumab is expected to enhance not only chemotherapy but also the efficacy of immune-checkpoint inhibitors through blockade of vascular endothelial growth factor–mediated immunosuppression. The aim of this trial is to demonstrate an additional effect of bevacizumab administered together with platinum combination therapy and the immune-checkpoint inhibitor atezolizumab in patients with advanced nonsquamous NSCLC. Methods: Cytotoxic chemotherapy–naïve patients aged 20 years or older with a performance status of 0 or 1 are randomly assigned in a 1:1 ratio to receive either atezolizumab plus pemetrexed-carboplatin (APP) or atezolizumab, pemetrexed-carboplatin, and bevacizumab (APPB). Patients with genetic driver alterations such as those affecting EGFR or ALK are included if they have experienced disease progression or unacceptable side effects during treatment with at least one approved tyrosine kinase inhibitor. After four cycles of induction therapy, maintenance therapy with atezolizumab plus pemetrexed or with atezolizumab plus pemetrexed plus bevacizumab is administered for up to 2 years until evidence of disease progression or development of unacceptable toxicity. The primary end point is progression-free survival (according to central image review). Secondary end points are progression-free survival (determined by the attending physician), overall survival, response rate, response duration, and adverse events. Stratification factors are PD-L1 tumor proportion score (≥50% vs. < 50%), stage, and driver gene alterations. We determined that, with a sample size of 350 patients (175 in each arm), the trial will have 80% power to show a hazard ratio for disease progression or death of 0.727 at a one-sided alpha level of 0.025 (as calculated on the basis of 311 such events) for comparison between the APPB and APP groups. Clinical trial information: 194565.

11503 Background: Olanzapine (OLZ) 10 mg added to standard antiemetic therapy including aprepitant (APR), palonosetron (PALO), and dexamethasone (DEX) has been recommended for the prevention of chemotherapy-induced nausea and vomiting (CINV) caused by highly emetogenic chemotherapy (HEC). Guidelines suggest that a dose of 5 mg should be taken into consideration in patients at risk of sedation. OLZ 5 mg showed an equivalent activity and favorable toxicity to somnolence in several phase II studies. We conducted a randomized, double-blind, placebo-controlled phase III trial to evaluate OLZ 5 mg in addition to standard antiemetic therapy for the prevention of CINV in patients receiving cisplatin-based chemotherapy. Methods: Patients receiving cisplatin (≥ 50 mg/m2) were randomly assigned to either OLZ 5 mg or placebo on days 1–4, combined with APR, PALO and DEX. The primary endpoint was complete response (CR), defined as no vomiting and no rescue medications in the delayed phase (24–120 h). A total of 690 patients were required to detect a 10% increase in CR from 65% in the placebo to 75% in the OLZ, with a one-sided alpha of 2.5% and a power of 80%. Results: A total of 710 patients were enrolled (OLZ 356 and placebo 354). CR in the delayed phase was 79.1% (95% CI: 74.9–83.3) in the OLZ 5 mg and 65.8% (95% CI: 60.9–70.8) in the placebo ( p < 0.001). Other efficacy results are summarized in Table. The most common treatment-related adverse events was somnolence (43.1% for OLZ vs. 33.0% for placebo). Conclusions: OLZ 5 mg combined with APR, PALO and DEX can be considered a new standard antiemetic therapy in patients receiving cisplatin-based chemotherapy. Clinical trial information: UMIN000024676. [Table: see text]

e20531 Background: Our previous phase 3 study established carboplatin plus the oral fluorinated pyrimidine formulation S-1 as a standard option for first-line treatment of advanced non–small cell lung cancer (NSCLC) (J Clin Oncol 2010; 28:5240). The importance of maintenance therapy for patients with advanced squamous NSCLC has been unknown, however. Methods: WJOG7512L was designed as a randomized phase 3 study to evaluate whether maintenance therapy with S-1 improves clinical outcome after induction therapy with carboplatin plus S-1 in such patients. Before randomization, patients received carboplatin (AUC of 5 on day 1 every 3 weeks) plus S-1 (40 mg/m2 twice per day on days 1 to 14 every 3 weeks) as induction therapy. Those who did not progress after four cycles of induction therapy were randomized to receive either S-1 plus best supportive care (BSC) or BSC alone. The primary objective was to confirm the superiority of S-1 plus BSC with regard to progression-free survival. Results: Of the 365 patients enrolled, 347 participated in the induction phase and 131 of these individuals were randomized to receive S-1 plus BSC ( n = 67) or BSC alone ( n = 64). Baseline demographics and clinical characteristics of the subjects, including the response to induction therapy, were well balanced. Patients receiving S-1 plus BSC showed a significantly reduced risk of disease progression compared with those receiving BSC alone (hazard ratio [HR], 0.548; 95% confidence interval [CI], 0.374–0.802; P = 0.0019). Median overall survival from randomization did not differ significantly between the two arms: 17.8 months for BSC alone and 16.7 months for S-1 plus BSC (HR, 0.890; 95% CI, 0.583–1.357). Time to deterioration in quality of life also showed no significant difference ( P = 0.8754 for FACT-TOI, P = 0.9016 for FACT-LCS). The incidence of adverse events during maintenance therapy was low, with neutropenia, anemia, and thrombocytopenia of grade 3 or 4 each occurring in ~1% to 4% of patients. Conclusions: Maintenance with S-1 plus BSC is an effective and well-tolerated treatment option for patients with advanced squamous NSCLC. Clinical trial information: UMIN000010396.

TPS9114Background: Nivolumab is one of the standard therapies for pretreated advanced non-small cell lung cancer (NSCLC). A correlation between PD-L1 expression on tumor cells and antitumor effects...