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Our data further support the importance of EGFR mutation with regard to gefitinib sensitivity. In addition to its predictive role, EGFR mutation confers significant survival benefits on NSCLC patients treated with gefitinib.

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267 Background: Atezo + bev has been approved globally for pts with unresectable HCC who have not received prior systemic therapy, based on results from IMbrave150 (NCT03434379). At a median of 8.6 mo follow-up, both coprimary endpoints were met, with statistically significant and clinically meaningful improvements observed with atezo + bev vs sor for OS (HR, 0.58 [95% CI, 0.42, 0.79]; P<0.001) and independently-assessed progression-free survival (PFS; per RECIST 1.1; HR, 0.59 [95% CI, 0.47, 0.76]; P<0.001) (Finn, et al. N Engl J Med 2020). Here, we report an updated OS analysis for IMbrave150. Methods: The global, multicenter, randomized, open-label, Phase III study IMbrave150 enrolled 501 systemic treatment–naive pts with unresectable HCC, ≥1 measurable untreated lesion (RECIST 1.1), Child-Pugh class A liver function and ECOG PS 0/1. Pts were randomized 2:1 to receive either atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sor 400 mg bid until unacceptable toxicity or loss of clinical benefit per investigator. This post hoc, descriptive OS analysis was conducted with 12 mo of additional follow up from the primary analysis. Results: 501 pts were enrolled, including 336 to atezo + bev and 165 to sor. At the clinical cut-off date of Aug 31, 2020, median follow-up was 15.6 mo and 280 OS events were observed. Median OS was 19.2 mo with atezo + bev vs 13.4 mo with sor (HR, 0.66 [95% CI, 0.52, 0.85]; P=0.0009). Survival at 18 mo was 52% with atezo + bev and 40% with sor. Survival benefit with atezo + bev over sor was generally consistent across subgroups and with the primary analysis. The updated objective response rate (ORR; 29.8% per RECIST 1.1) with atezo + bev was in line with the primary analysis, with more pts achieving complete response (CR; 7.7%) than previously reported. Additional response data are in Table. Safety was aligned with the primary analysis, with no new signals identified. Conclusions: IMbrave150 showed consistent clinically meaningful treatment benefit and safety with 12 mo of additional follow-up. The combination provides the longest survival seen in a front-line Phase III study in advanced HCC, confirming atezo + bev as a standard of care for previously untreated, unresectable HCC. Clinical trial information: NCT03434379. [Table: see text]

4012 Background: NIVO monotherapy (mono) is approved for sorafenib (SOR)-treated pts with HCC based on data from CheckMate 040 (NCT01658878), which reported an objective response rate (ORR) of 14% and median overall survival (mOS) of 16 months (mo). This is the first report of efficacy and safety of the NIVO + IPI combination in SOR-treated pts with aHCC. Methods: Pts were randomized to 3 arms: [A] NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) or [B] NIVO 3 mg/kg + IPI 1 mg/kg Q3W (4 doses), each followed by NIVO 240 mg Q2W, or [C] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W. Treatment continued until intolerable toxicity or disease progression. Primary endpoints included safety and tolerability. Secondary endpoints included ORR (BICR per RECIST v1.1), duration of response (DOR), disease control rate (DCR), and OS. Cutoff was 25 Sep 2018. Results: 148 SOR-treated pts were randomized. Minimum follow-up for OS from last pt randomization date to data cutoff was 24 mo. At baseline: 88% had vascular invasion or extrahepatic spread, 91% had BCLC stage C, 84% discontinued SOR due to disease progression and 14% due to toxicity. Overall, ORR was 31% (7 had a complete response [CR]) with a median DOR of 17 mo; DCR was 49% and 24-mo OS rate was 40%. Pts in arm A had a mOS of 23 mo and 4 pts had a CR. The table shows additional efficacy results by arm. Overall, NIVO + IPI was well tolerated; 37% of pts had a grade 3–4 treatment-related adverse event (TRAE; most common: pruritus and rash); 5% had grade 3–4 TRAEs leading to discontinuation. Conclusions: NIVO + IPI led to clinically meaningful responses and had an acceptable safety profile in SOR-treated pts, with an ORR twice that of NIVO mono (31% and 14%, respectively). Pts in arm A had the most promising mOS of 23 mo. Clinical trial information: NCT01658878. [Table: see text]

IntroductionTriple negative breast cancer (TNBC) has a poorer survival, despite a higher response rate to neoadjuvant chemotherapy. The purpose of this study was to identify the predictive or prognostic value of Ki-67 among patients with TNBC treated with neoadjuvant chemotherapy, and the role of Ki-67 in further classification of TNBC.MethodsA total of 105 TNBC patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were included in the present study. Pathologic complete response (pCR) rate, relapse-free survival (RFS), and overall survival (OS) were compared according to the level of Ki-67.ResultspCR was observed in 13.3% of patients. TNBC with high Ki-67 expression (≥10%) showed a higher pCR rate to neoadjuvant chemotherapy than TNBC with low Ki-67 expression. None of the low Ki-67 group achieved pCR (18.2% in the high Ki-67 group vs. 0.0% in the low Ki-67 group, P = 0.019). However, a high Ki-67 expression was significantly associated with poor RFS and OS in TNBC, despite a higher pCR rate (P = 0.005, P = 0.019, respectively). In multivariate analysis, high Ki-67 was an independent prognostic factor for RFS in TNBC (hazard ratio = 7.82, P = 0.002). The high Ki-67 group showed a similar pattern of recurrence with overall TNBC, whereas the low Ki-67 group demonstrated a relatively constant hazard rate for relapse.ConclusionsTNBC with high Ki-67 was associated with a more aggressive clinical feature despite a higher pCR rate. High proliferation index Ki-67 can be used for further classification of TNBC into two subtypes with different responses and prognosis.

IntroductionBody composition has emerged as a prognostic factor in cancer patients. We investigated whether sarcopenia at diagnosis and loss of skeletal muscle during palliative chemotherapy were associated with survival in patients with pancreatic cancer.MethodsWe retrospectively reviewed the clinical outcomes of pancreatic cancer patients receiving palliative chemotherapy between 2003 and 2010. The cross-sectional area of skeletal muscle at L3 by computed tomography was analyzed with Rapidia 3D software. We defined sarcopenia as a skeletal muscle index (SMI)< 42.2 cm2/m2 (male) and < 33.9 cm2/m2 (female) using ROC curve.ResultsAmong 484 patients, 103 (21.3%) patients were sarcopenic at diagnosis. Decrease in SMI during chemotherapy was observed in 156 (60.9%) male and 65 (40.6%) female patients. Decrease in body mass index (BMI) was observed in 149 patients (37.3%), with no gender difference. By multivariate analysis, sarcopenia (P< 0.001), decreasedBMI and SMI during chemotherapy (P = 0.002, P = 0.004, respectively) were poor prognostic factors for overall survival (OS). While the OS of male patients was affected with sarcopenia (P< 0.001) and decreased SMI (P = 0.001), the OS of female patients was influenced with overweight at diagnosis (P = 0.006), decreased BMI (P = 0.032) and decreased SMI (P = 0.014). Particularly, while the change of BMI during chemotherapy did not have impact on OS within the patients with maintained SMI (P = 0.750), decrease in SMI was associated with poor OS within the patients with maintained BMI (HR 1.502; P = 0.002).ConclusionsSarcopenia at diagnosis and depletion of skeletal muscle, independent of BMI change, during chemotherapy were poor prognostic factors in advanced pancreatic cancer.

Purpose: Mutations in epidermal growth factor receptor (EGFR) are strongly predictive of gefitinib efficacy in non^small-cell lung cancer. However, the presence of EGFR mutant nonresponses and nonmutant responses points out the need for more comprehensive analysis. Patients and Methods: For 69 non^small-cell lung cancer patients treated with gefitinib, we have extended our analysis to EGFR gene copy number by fluorescence in situ hybridization, mutations in K-ras, HER2, and exon 20 of EGFR by direct sequencing, and phosphatase and tensin homologue expression by immunohistochemistry, in addition to EGFR exons 18, 19, and 21, and phosphorylations of Akt and extracellular signal^regulated kinase reported previously. Results: EGFR mutation and high gene copy number were associated with better objective response in univariate analysis. However, only gefitinib-sensitive EGFR mutation was independently predictive of both response (P = 0.011) and survival (P = 0.002) in multivariate analysis. No patients with K-ras mutation, including two EGFR mutants, showed response. In EGFR nonmutants, patients with either K-ras mutation or p-Akt overexpression exhibited poor response and time-to-progression whereas patients with high gene copy number tended to have better outcomes in univariate analysis. In multivariate analysis of time-to-progression in EGFR nonmutants, K-ras mutation or p-Akt overexpression was associated with shorter time-to-progression (P = 0.017). No patient with HER2 mutation showed response to gefitinib. Reduced phosphatase and tensin homologue expression was not associated with gefitinib sensitivity. Conclusion: Gefitinib-sensitive EGFR mutation is the single most important predictor of gefitinib sensitivity. In addition to EGFR mutation, K-ras mutation and Akt phosphorylation aid in better prediction of gefitinib responsiveness in non^small-cell lung cancer.