Osimertinib is a standard treatment for epidermal growth factor receptor (EGFR)-mutated, T790M-positive patients with progression during EGFR-tyrosine kinase inhibitor (TKI) therapy. Osimertinib, a ...third-generation EGFR-TKI, allows progression-free survival of around 10 months, but its toxicity is well-tolerated compared with other EGFR-TKIs. Preclinical and clinical evidence suggests that EGFR-TKI may work synergistically with vascular endothelial growth factor inhibitors.
We therefore plan a phase I/II study to investigate this possibility. In phase I, the primary endpoint is assessment of the tolerability of osimertinib and bevacizumab in 6 patients. Phase II then explores the efficacy of combined treatment compared with osimertinib monotherapy with progression-free survival as the primary endpoint. Secondary endpoints are overall response rate, time to treatment failure, overall survival, and safety. Eighty patients will be enrolled in phase II.
The data of sequential therapy of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) in clinical practice have been limited.
We reviewed the clinical data of patients with ...ALK-rearranged non-small cell lung cancer who received crizotinib (CRZ) or alectinib (ALEC) between May 2012 and December 2016. Patients were divided into two groups based on the first-administered ALK-TKI, the CRZ or ALEC group. The combined time-to-treatment failure (TTF) was defined as the sum of the ‘TTF of CRZ’ plus the ‘TTF of ALEC’ if patients were treated with CRZ followed by ALEC in the CRZ group. The primary end-point is the comparison between the combined TTF and the TTF of ALEC in the ALEC group.
Of 864 patients enrolled from 61 institutions, 840 patients were analysed. There were 535 of 305 patients in the CRZ/ALEC groups. The combined TTF in the CRZ group was significantly longer than TTF in the ALEC group (median, 34.4 versus 27.2 months; hazard ratio HR, 0.709; P = 0.0044). However, there was no significant difference in overall survival (OS) between the patients who received ALEC after CRZ in the CRZ group and the patients in the ALEC group (median, 88.4 months versus. not reached; HR, 1.048; P = 0.7770). In the whole population, the CRZ group had a significantly shorter OS than the ALEC group (median, 53.6 months versus not reached; HR, 1.821, P < 0.0001).
The combined TTF in the CRZ group was significantly longer than the TTF in the ALEC group; however, OS benefit of sequential therapy against ALEC as the first ALK-TKI was not shown.
•Large-scale real-world data showed longer progression-free survival of alectinib than crizotinib.•But, propensity score analysis of overall survival could not show the superiority of alectinib.•Poor responders to crizotinib had poorer response also to alectinib.•Ceritinib or lorlatinib showed activity even after crizotinib or alectinib therapy.•Meanwhile, immunotherapy could not show clinical benefit in our data.
3
Background: HER2-low expression breast cancer is a new classification and began to receive attention after trastuzumab deruxtecan showed its effect on this classification. As for endocrine ...therapies, HER2-low expression seemed not to affect the efficacy of CDK4/6 inhibitors in a few retrospective studies. However, previous data on the effectiveness of endocrine therapies other than CDK4/6 inhibitors for HER2-low metastatic breast cancer (mBC) are still limited. This study aims to evaluate the difference in endocrine therapy between HER2-low and HER2-zero mBC. Methods: We retrospectively reviewed the clinical data of mBC patients prescribed aromatase inhibitors, tamoxifen or fulvestrant, and/or CDK4/6 inhibitors at our department between May 2012 and December 2022. Patients were excluded if they received chemotherapy before endocrine therapy, lacked data on HER2 score, or discontinued treatment before the first image evaluation. The data cutoff date was 15th March 2023. We analyzed the difference in progression-free survival (PFS) of the first-line endocrine monotherapy and the first-line CDK4/6 inhibitors between HER2-low and HER2-zero mBC by logrank analysis. Results: Of 126 patients who received the first-line endocrine monotherapy, 22 were HER2-zero, and 104 were HER2-low. In the HER2-zero group, six patients received tamoxifen, and 16 received AIs. In the HER2-low group, 29 patients received tamoxifen, 63 received AIs, and 12 received fulvestrant. The median PFS was 27.7 months with the HER2-zero group and 15.6 months with the HER2-low group. This was not statistically significant (P=0.196), but the Kaplan-Meier curve showed that PFS tended to be longer with the HER2-zero group. This trend was also observed in patients who received AIs. Of 52 patients who received CDK4/6 inhibitors as a first-line treatment, ten were HER2-zero, and 42 were HER2-low. The median PFS was NA with the HER2-zero group and 22.8 months with the HER2-low group, and no significant differences were detected. Conclusions: In this study, there were no statistically significant differences in the PFS of the first-line endocrine monotherapy and CDK4/6 inhibitors between HER2-low and HER2-zero mBC. However, the Kaplan-Meier curve showed that the PFS of endocrine therapy tended to be longer in the HER2-zero group. Further studies are warranted.
Background
A randomized phase 3 study was performed to investigate the efficacy and safety of maintenance therapy with S‐1 after induction therapy with carboplatin plus S‐1 in patients with advanced ...squamous non–small cell lung cancer (NSCLC).
Methods
Chemotherapy‐naive patients with advanced or relapsed squamous NSCLC were treated with carboplatin (area under the curve of 5 on day 1 every 3 weeks) plus S‐1 (40 mg/m2 twice per day on days 1‐14 every 3 weeks) as induction therapy. Patients who did not progress after 4 cycles of induction therapy were randomized to receive either S‐1 plus best supportive care (BSC) or BSC alone. The primary objective of the study was to confirm the superiority of S‐1 plus BSC in comparison with BSC alone with respect to progression‐free survival.
Results
Of the 365 patients enrolled in the study, 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). The risk of disease progression was significantly lower for patients in the S‐1 plus BSC arm than those in the BSC‐alone arm (hazard ratio, 0.548; 95% confidence interval, 0.374‐0.802; P = .0019). The most common toxicities during maintenance therapy with S‐1 included anorexia, anemia, and fatigue, but most cases were not severe.
Conclusions
Continued maintenance with S‐1 plus BSC is an effective and well‐tolerated treatment option for patients with advanced squamous NSCLC previously treated with carboplatin plus S‐1.
The West Japan Oncology Group 7512L study compares S‐1 maintenance therapy with best supportive care alone in patients with advanced squamous non–small cell lung cancer after induction therapy with carboplatin plus S‐1. The primary endpoint of the study has been met with the detection of a significant improvement in progression‐free survival with S‐1 maintenance therapy.
Background
In CheckMate 227 Part 1 (NCT02477826), first-line nivolumab plus ipilimumab demonstrated long-term durable overall survival (OS) benefit versus chemotherapy in patients with metastatic ...non-small cell lung cancer (NSCLC), regardless of tumor programmed death ligand 1 (PD-L1) expression. We report results in Japanese patients with ≥ 5-year follow-up.
Methods
Adults with stage IV/recurrent NSCLC without
EGFR/ALK
aberrations were randomized 1:1:1 to nivolumab plus ipilimumab, nivolumab alone, or chemotherapy (patients with tumor PD-L1 ≥ 1%), or nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (patients with tumor PD-L1 < 1%). Five-year efficacy and safety were assessed in Japanese patients.
Results
At 62.1 months’ minimum follow-up, 143 Japanese patients with PD-L1 ≥ 1% or < 1% were randomized to nivolumab plus ipilimumab (
n
= 66) or chemotherapy (
n
= 77). Five-year OS rates were 46% with nivolumab plus ipilimumab versus 34% with chemotherapy (PD-L1 ≥ 1%) and 36% versus 19% (PD-L1 < 1%). Median duration of response was 59.1 versus 7.1 months (PD-L1 ≥ 1%) and 17.3 versus 3.0 months (PD-L1 < 1%). Among 5-year survivors treated with nivolumab plus ipilimumab (PD-L1 ≥ 1% and < 1%;
n
= 27), 59% (95% CI, 39%–75%) were off treatment for ≥ 3 years without receiving subsequent therapy. No new safety signals were observed.
Conclusions
At 5-year follow-up, nivolumab plus ipilimumab continued to show long-term durable clinical benefit versus chemotherapy, regardless of tumor PD-L1 expression. Consistent with findings for the global population, these data support the use of nivolumab plus ipilimumab as first-line treatment in Japanese patients with metastatic NSCLC.
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