Combination therapy with immune checkpoint inhibitors and cytotoxic chemotherapies (chemoimmunotherapy) is associated with significantly better survival outcomes than cytotoxic chemotherapies alone in patients with advanced non-small cell lung cancer (NSCLC). However, there are no prognostic markers for chemoimmunotherapy. The prognostic nutritional index (PNI) and lung immune prognostic index (LIPI) are prognostic biomarkers for immune checkpoint inhibitor (ICI) monotherapy or cytotoxic chemotherapies. Thus, we aimed to examine whether these factors could also be prognostic markers for chemoimmunotherapy. We retrospectively examined 237 patients with advanced NSCLC treated with chemoimmunotherapy. In the total group, the median overall survival (OS) was not reached, and the median progression-free survival (PFS) was 8.6 months. Multivariate analysis of OS and PFS revealed significant differences based on PNI and LIPI. Programmed cell death ligand 1 (PD-L1) was also significantly associated with OS and PFS. PNI and a PD-L1 tumor proportion score (TPS) of <50% and poor LIPI (regardless of PD-L1 TPS) were associated with poor prognosis. PNI and LIPI predicted survival outcomes in patients with advanced NSCLC treated with chemoimmunotherapy, especially in patients with PD-L1 TPS <50%. For patients in this poor category, chemoimmunotherapy may result in a worse prognosis than expected.

Background: First-line chemoimmunotherapy (CIT) has improved overall survival (OS) and progression-free survival (PFS) outcomes among patients with non-small cell lung cancer (NSCLC). The immunological and nutritional statuses of patients fluctuate during treatment using immune checkpoint inhibitors, and are closely related to treatment outcomes. However, it is unclear whether these markers are significant in patients who are receiving CIT. Methods: This retrospective single-center study evaluated 34 consecutive Japanese patients with NSCLC who were treated using first-line CIT. Previously reported markers that reflect immunological and nutritional statuses were evaluated at three time points: at the start of CIT, after three weeks, and at the end of induction therapy. Results: The median PFS was 7.2 months (95% confidence interval: 6.3 monthsnot reached) and the median OS was not reached (95% confidence interval: 9.6 months-not reached). The PFS duration was significantly associated with the baseline neutrophil-to-lymphocyte ratio and the three-week values for the modified Glasgow prognostic score, C-reactive protein-albumin ratio, prognostic nutrition index, and advanced lung cancer inflammation index. The OS duration was significantly associated with the pre-treatment values for the neutrophil-tolymphocyte ratio and advanced lung cancer inflammation index, as well as the prognostic nutrition index at the end of induction therapy. Conclusions: Immunological and nutritional markers could be useful for predicting the outcomes of CIT for Japanese patients with advanced non-small cell lung cancer. The timing of their evaluation may also be important.

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are life-threatening dermatologic adverse events in the same category, caused by a delayed-type drug hypersensitivity reaction. Although skin toxicity is common during treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), osimertinib-associated TEN is quite rare—thus far, only one report has been published from China. We report a case of an 80-year-old Japanese woman with lung adenocarcinoma harboring an EGFR-sensitizing mutation who was treated with osimertinib as the first-line treatment. Forty-six days after osimertinib induction, diffuse erythematous rash rapidly spread over the patient’s trunk along with vesicles and purpuric macules; furthermore, she developed targetoid erythema on the face. Despite osimertinib discontinuation and corticosteroid treatment, diffuse erythema with Nikolsky’s sign, general epidermal detachment, erosion and loose blisters developed over her entire body including the face. Based on her symptoms, TEN was diagnosed and thus, intravenous immunoglobulin was immediately administered for 4 days. The treatment ameliorated TEN-associated skin toxicity and caused epithelialization. Reports on osimertinib-associated SJS/TEN are scarce and only one report each on SJS and TEN from China is available. This is the first report of osimertinib-associated TEN from Japan. Cases of EGFR-TKI-associated SJS/TEN have been reported predominantly from Asian countries, suggesting ethnicity and genetic linkage play a role in the underlying mechanism.

The prognoses of patients with non-small-cell lung cancer (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangement have dramatically improved with the use of ALK tyrosine kinase inhibitors. Although immunological and nutritional markers have been investigated to predict outcomes in patients with several cancers, their usefulness in targeted therapies is scarce, and their significance has never been reported in patients receiving first-line treatment with alectinib. Meanwhile, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (PLR) has been investigated during crizotinib treatment. This multicenter retrospective study evaluated 42 consecutive Japanese patients with ALK-positive NSCLC who received first-line treatment with alectinib. Immunological and nutritional markers were evaluated at baseline and 3 weeks after alectinib introduction, and their significance in predicting progression-free survival (PFS) was explored. PFS duration was significantly associated with baseline PLR (hazard ratio (HR): 2.49, p = 0.0473), systemic immune-inflammation index (SII; HR: 2.65, p = 0.0337), prognostic nutrition index (PNI; HR: 4.15, p = 0.00185), and the 3-week values for SII (HR: 2.85, p = 0.0473) and PNI (HR: 3.04, p = 0.0125). Immunological and nutritional markers could be useful in predicting the outcomes of first-line treatment with alectinib. Since PLR and SII consist of platelet counts, platelet count could be an important constituent of these markers.

Atezolizumab was the first immune checkpoint inhibitor (ICI) to be introduced as a first‐line treatment option for extensive‐stage small cell lung cancer (ES‐SCLC), in combination with carboplatin and etoposide (CE) chemotherapy. However, SCLC treatment options after progression to first‐line chemotherapy are limited, warranting the readministration of previously used drugs. In combination with atezolizumab, CE readministration may theoretically be effective, based on two tentative mechanisms: its additive and synergistic effects on cytotoxic chemotherapy. The additive effect is based on the IFCT‐1603 trial in which the Kaplan‐Meier estimates of both progression‐free survival (PFS) and overall survival (OS) in the atezolizumab group exhibited a tail plateau in the selected population. Conversely, an anti‐PD‐L1 antibody synergistic effect on platinum compounds was assessed in a preclinical study, which was reinforced by clinical data. Thus, atezolizumab in combination with CE may be a treatment option in heavily treated patients. Here, we describe the first case of a heavily treated ES‐SCLC patient treated with chemoimmunotherapy, resulting in a partial response and a durable PFS. Key points Significant findings of the study and what this study adds CE readministration with atezolizumab may be effective based on two tentative mechanisms. Additive and synergistic effects of atezolizumab on CE have been previously suggested via a clinical trial and preclinical study, respectively. This is reflected in the current case in clinical settings.