Purpose
This study evaluated the efficacy and safety of nivolumab treatment beyond progressive disease (PD) in non-small cell lung cancer (NSCLC).
Patients/methods
Medical records of consecutive ...patients with advanced NSCLC who received nivolumab between December 2015 and December 2018 were reviewed. Clinical outcomes of three groups of eligible patients who received nivolumab as a second-line treatment after PD were compared based on Response Evaluation Criteria in Solid Tumors v1.1. We conducted subgroup analyses in patients with and without new lesions at first PD.
Results
Twenty-eight patients continued nivolumab treatment beyond PD (TBP). Post PD, 46 patients switched to other anti-cancer treatment (OAT), and 21 received no further anti-cancer treatment (NAT). There were no significant differences in overall survival (OS) or survival post progression (SPP) between TBP and OAT groups (OS: 15.6 vs. 13.4 months,
P
= .40, SPP: 12.2 vs. 9.3 months,
P
= .42). Subgroup analyses indicated that among patients without new lesions at first PD, SPP was longer in the TBP than in the OAT groups (12.6 vs. 9.3 months,
P
= .22, HR: 0.64; 95% CI 0.31‒1.31). The frequency of immune-related adverse events leading to discontinuation during nivolumab beyond PD was equivalent to that for pre-PD (10.7 vs. 12.6%).
Conclusions
No significant benefits were associated with continuation of nivolumab for advanced NSCLC patients. Continuation of nivolumab beyond PD could be a more useful option in patients without new lesions at first PD. Treatment-related toxicities require attention during nivolumab treatment not only before PD but also beyond PD.
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) improve the prognosis of EGFR-mutant non-small cell lung cancer (NSCLC). However, other human epidermal growth factor receptor ...(HER) families contribute to EGFR-TKI resistance. The HER3 ligand heregulin is aberrantly expressed in NSCLC. Previously, heregulin genomic induction in an EGFR-mutant NSCLC cell line caused EGFR-TKI resistance, except against 2nd-generation EGFR-TKIs, which uniquely blocked the pan-HER family. However, the clinical relevance of heregulin is unclear in EGFR-mutant NSCLC. Here, we aimed to explore the implication of heregulin in patients with EGFR-mutant NSCLC treated with EGFR-TKIs.
Soluble heregulin was immunologically measured in the plasma of patients with EGFR-mutant NSCLC. Cut-off values were determined via 1-year progression-free survival (PFS) receiver operating characteristic curve. Relationship between soluble heregulin and PFS, after EGFR-TKI therapy, was analyzed using a Cox proportional hazards model.
Seventy-six patients were enrolled, of which 44 were treated with 1st-generation, 29 with 2nd-generation, and 3 with 3rd-generation EGFR-TKIs. Soluble heregulin levels were found to vary (range: 274–7,138pg/mL, median: 741.5pg/mL). Among patients treated with 1st- and 3rd-generation EGFR-TKIs, those with high heregulin (n=22, > 800pg/mL) had a shorter PFS than those with low heregulin (n=25, < 800pg/mL) levels; median PFS of 322 and 667 days were, respectively, observed. Cox proportional hazards model indicated a trend toward resistance (HR: 1.797, 95% CI: 0.833–3.877), except with 2nd-generation EGFR-TKIs (HR: 0.879, 95% CI: 0.325–2.376).
Results showed soluble heregulin to potentially correlate with EGFR-TKI resistance, though not so for 2nd-generation EGFR-TKIs, in patients with EGFR-mutant NSCLC. Therefore, 2nd-generation EGFR-TKIs warrant comparative clinical examination regarding their anti-cancer efficacy in heregulin-expressing NSCLC.
The authors.
Boehringer Ingelheim.
K. Yonesaka: Honoraria (self), Research grant / Funding (institution): Boehringer ingelheim. E. Iwama: Research grant / Funding (institution): Boehringer Ingelheim. H. Hayashi: Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim. S. Suzuki: Research grant / Funding (institution): Boehringer Ingelheim. R. Kato: Research grant / Funding (institution): Boehringer Ingelheim. S. Watanabe: Research grant / Funding (institution): Boehringer Ingelheim. T. Takahama: Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim. J. Tanizaki: Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim. K. Tanaka: Research grant / Funding (institution): Boehringer Ingelheim. M. Takeda: Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim. K. Sakai: Research grant / Funding (institution): Boehringer Ingelheim. K. Azuma: Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim. Y. Chiba: Research grant / Funding (institution): Boehringer Ingelheim. S. Atagi: Honoraria (self): Boehringer Ingelheim. K. Nishio: Research grant / Funding (self), Research grant / Funding (institution): Boehringer Ingelheim. I. Okamoto: Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca. K. Nakagawa: Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Boehringer ingelheim; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Bristol-Myers Squibb.
A phase II trial was conducted to evaluate the efficacy and toxicity of the Egorin's carboplatin dosing formula with 14-day oral etoposide in 38 elderly patients with small-cell lung cancer (SCLC). ...The overall response rate was 81%. Median survival times were 15.1 months for 16 limited-disease (LD) and 8.6 months for 22 extensive-disease (ED) patients. Myelosuppression was the principal side-effect. This regimen is an active regimen in the treatment of elderly SCLC patients.
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