Clinical lung cancer最新文献

Lobectomy has been the standard treatment for stage I lung cancer in healthy patients, largely based on a randomized trial published in 1995. Nevertheless, research has continued regarding the role of sublobar resection. Three additional randomized trials addressing resection extent in healthy patients have recently been published. These 4 trials involve differences in design, eligibility, interventions, and intraoperative processes. Patients were ineligible if intraoperative assessment demonstrated stage > IA or inadequate resection margins. All trials consistently show no differences in perioperative morbidity, mortality, and postoperative changes in lung function between sublobar resection and lobectomy—consistent with other nonrandomized evidence. Long-term outcomes are generally encouraging of lesser resection, but some inconsistencies are apparent. The 2 larger recent trials demonstrated no overall survival difference while the others suggested better survival after lobectomy versus sublobar resection. Recurrence-free survival was found to be the same after lobectomy versus sublobar resection in 3 trials, despite higher locoregional recurrences after sublobar resection. The low 5-year recurrence-free survival (64%, regardless of resection extent) in 1 recent trial highlights the need for further optimization. Thus, there is high-level evidence that sublobar resection is a reasonable alternative to lobectomy in healthy patients. However, variability in long-term results suggests that aspects of patients, tumors and interventions need to be better understood. Therefore, we propose to apply sublobar resection cautiously; especially because there are no short-term benefits. Sublobar resection requires careful attention to intraoperative details (nodes, margins), and may be best suited for less aggressive (eg, ground glass, slow growing) tumors.

Introduction

Atezolizumab following platinum chemotherapy and complete pulmonary resection has become the new standard of adjuvant care for patients with stage II-III non-small cell lung cancer (NSCLC) expressing programmed death-ligand 1 (PD-L1). However, the efficacy and safety of postoperative adjuvant therapy and subsequent atezolizumab in patients aged 75 and older have not been established.

Methods

Patients with completely resected stage II–III NSCLC aged 75 and older will be prospectively registered in this single-arm phase II study. The enrolled patients will receive cisplatin plus vinorelbine (CDDP + VNR) followed by atezolizumab for up to 12 months. PD-L1 expression in at least 1% of cells will be confirmed by immunohistochemical staining. We plan to enroll 33 patients over 1 year at 25 institutions in Japan. The primary endpoint is the completion rate of adjuvant treatment (CDDP + VNR initiation to atezolizumab completion).

Conclusion

The present study represents the first prospective trial of the tolerability of postoperative adjuvant therapy with immune checkpoint inhibitors in elderly individuals. The results of this trial might help promote postoperative adjuvant immunotherapy in the future for the elderly.

Introduction

The LIPI, based on pretreatment derived neutrophils/[leukocytes-neutrophils] ratio (dNLR) and LDH, is associated with immune checkpoint inhibitors (ICI) outcomes in advanced non–small-cell lung cancer (NSCLC). We aimed to assess baseline LIPI correlation with durvalumab consolidation outcomes in the locally advanced setting.

Material and Methods

Multicentre retrospective study (330 patients) with stage III unresectable NSCLC treated with durvalumab after chemo-radiotherapy between April 2015 and December 2020; 65 patients treated with chemo-radiotherapy only. Baseline LIPI characterized 3 groups: good (dNLR≤3+LDH≤ULN), intermediate (dNLR>3/LDH>ULN) and poor (dNLR>3+LDH>ULN). Primary endpoint was overall survival (OS).

Results

In the durvalumab cohort, median age was 67 years, 95% smokers, 98% with a performance status of 0-1; 60% had nonsquamous histology and 16% a PD-L1 expression <1%. Radiotherapy was delivered concurrently in 81%. LIPI was evaluable in 216 patients: 66% good, 31% intermediate, 3% poor.

LIPI significantly correlated with median OS (median follow-up: 19 months): 18.1 months vs. 47.0 months vs. not reached in poor, intermediate and good LIPI groups, respectively (P = .03). A trend between objective response rate and LIPI groups was observed: 0% vs. 41% vs. 45%, respectively (P = .05). The pooled intermediate/poor LIPI group was associated with shorter OS (HR 1.97; P = .03) and higher risk of progressive disease (OR 2.68; P = .047). Survivals and response were not influenced in the control cohort.

Conclusion

Baseline LIPI correlated with outcomes in patients with locally advanced NSCLC treated with durvalumab consolidation, but not in those who only received chemo-radiotherapy, providing further evidence of its prognostic and potential predictive role of ICI benefit in NSCLC.

Pulmonary atypical carcinoid (AC) is an extremely rare neuroendocrine tumor. The neurotrophic tropomyosin receptor kinase (NTRK) fusions are reported in only 0.5% of nonsmall cell lung cancer, and are more rare in AC with only one previously reported case. Currently, there is little established evidence on the optimal therapeutic strategies and prognosis for advanced cases. We present a female patient with metastatic AC after complete resection. Due to low expression of somatostatin receptor in this case, somatostatin analogs and peptide receptor radionuclide therapy were not available. After pursuing other alternative treatments, including chemotherapy (ie, carboplatin, etoposide, capecitabine, temozolomide, and paclitaxel), everolimus, and atezolizumab, she returned with significant progression, including innumerable subcutaneous nodules, left pleura metastasis, multiple bone metastases, and brain metastases. New biopsy analysis revealed an ETV6-NTRK2 fusion. She was immediately administered the first-generation tropomyosin receptor kinase inhibitor entrectinib at a dose of 600 mg q.d. A subsequent month of treatment resulted in a complete response in all of the metastatic lung lesions. To date, she has maintained sustained benefit for at least 1 year from initiation of entrectinib. Here, we present the first case of a female patient with metastatic AC harboring the ETV6-NTRK2 fusion, and successfully treated with entrectinib, providing evidence for the application of entrectinib in patients with NTRK-positive AC, and underscoring the critical role of molecular profiling for such cases.

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  In the phase 3 POSEIDON study, patients with EGFR/ALK wild-type metastatic NSCLC (mNSCLC) were randomized (1:1:1) to first-line tremelimumab plus durvalumab and platinum-based chemotherapy (T + D + CT), durvalumab plus chemotherapy (D + CT), or chemotherapy alone (CT), with stratification by programmed cell death ligand-1 (PD-L1) tumor cell (TC) expression level (≥ 50% vs. < 50%), disease stage, and histology.

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  In alpha-controlled analyses in the ITT population, T + D + CT significantly improved overall survival (OS) and progression-free survival (PFS) versus CT, leading to approval for this regimen. PFS was also significantly improved with D + CT versus CT; a trend for improved OS did not reach statistical significance.

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  Patients with PD-L1-low or -negative tumors may show primary resistance to anti-PD-(L)1 therapy, with real-world data suggesting that treatment benefits observed in trials do not always translate into optimal outcomes in clinical practice.

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  Here we report outcomes from POSEIDON from post-hoc exploratory analyses in subgroups with PD-L1 TC ≥ 1% versus < 1%.

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  Among 1012/1013 randomized patients with known PD-L1 status, 644 (63.6%) versus 368 (36.4%) had PD-L1 TC ≥ 1% versus < 1%.

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  Both T + D + CT and D + CT appeared to show OS/PFS benefit versus CT in patients with PD-L1 TC ≥ 1%.

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  Consistent with the role of cytotoxic T-lymphocyte-associated antigen 4 and PD-L1 in the immune response, the addition of tremelimumab to first-line durvalumab and chemotherapy also conferred clinical benefit to patients with PD-L1 TC < 1% mNSCLC.

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  This exploratory subgroup analysis of POSEIDON supports T + D + CT as a first-line treatment option for patients with mNSCLC irrespective of PD-L1 expression, including the harder-to-treat subgroup with PD-L1 TC < 1%.

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  Resectable NSCLC has a high recurrence rate of 30-55%. Neoadjuvant, adjuvant, or perioperative combination of ICIs and CTX improved survival outcomes and response rates compared to CTX alone. Our meta-analysis of 11 RCTs suggests that neoadjuvant or perioperative treatment resulted in more favorable OS, EFS, and pathological response rates, supporting the use of these treatment regimens in this patient population. Meanwhile, adjuvant ICI significantly improved DFS with a trend towards improvement in OS.

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  Positive PD-L1 status, non-squamous histology, and stage III achieved a more profound EFS advantage. A longer, perioperative regimen might be required to improve survival outcomes in subgroups that obtained less advantage from ICI, such as squamous histology. Other clinical factors, such as age, sex, race, and geographical location, did not modify the benefit obtained from ICI, exhibiting the generalizability of ICI in different demographics.

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  Head-to-head studies to compare neoadjuvant versus perioperative ICI and the duration of adjuvant ICI should be further investigated to determine the optimal sequence and duration of ICI in patients with resectable NSCLC.

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  With the increasing emphasis on early detection of lung cancer through lung cancer screening programs and incidental lung nodule programs, identifying and measuring clinically relevant patient-centered outcomes is critical.

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  This study aimed to characterize factors associated with nonmalignant surgical resection among patients with suspicious pulmonary nodules, focusing on comparisons among individuals with screen-detected versus incidental lung nodules. Individuals with screen-detected or incidental lung nodules may experience differing nodule management strategies and surgical outcomes.

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  In addition, receipt of more intensive lung nodule management may be associated with lower odds of nonmalignant resection. These findings underscore the need for further investigation of best practices in lung nodule management by multidisciplinary teams.

Introduction

Exon 20 insertions (ex20ins) mutations of the EGFR gene account for 1% to 2% of all non–small-cell lung cancers (NSCLCs). Targeted therapies have been developed to treat this cancer type but have not been studied in head-to-head trials. Our objective was to use a matching-adjusted indirect comparison (MAIC) to assess the efficacy of mobocertinib and amivantamab in patients with NSCLC EGFR ex20ins mutations who were previously treated with platinum-based chemotherapy.

Materials and Methods

An unanchored MAIC was conducted to estimate the treatment effects of mobocertinib and amivantamab using individual-level data from the mobocertinib phase I/II single-arm trial (NCT02716116) and published data from the amivantamab single-arm CHRYSALIS trial (NCT02609776). Confirmed overall response rate (cORR), progression-free survival (PFS), overall survival (OS), and duration of response (DoR) were assessed.

Results

Both trials were comparable in terms of study population, study design, and outcome definitions and included 114 patients who received mobocertinib and 114 patients who received amivantamab. After MAIC weighting, all reported baseline characteristics were balanced between mobocertinib and amivantamab. The weighted odds ratio (OR) [95% confidence interval (CI)] comparing mobocertinib to amivantamab was 0.56 (0.30-1.04) for independent review committee (IRC)-assessed cORR and 0.98 (0.53-1.82) for investigator (INV)-assessed cORR. The weighted hazard ratio (HR) comparing mobocertinib to amivantamab was 0.74 (0.51-1.07) for IRC-assessed PFS, 0.92 (0.57-1.48) for OS, and 0.59 (0.30-1.18) for INV-assessed DoR.

Conclusion

MAIC analysis showed that mobocertinib and amivantamab had similar efficacy in patients with NSCLC harboring EGFR ex20ins mutations whose disease progressed during or after platinum-based chemotherapy. These findings may benefit patients by supporting future treatment options.

Background

Several regulatory agencies have approved the use of the neoadjuvant chemo-immunotherapy for resectable stage II and III of non-small cell lung cancer (NSCLC) and numerous trials investigating novel agents are underway. However, significant concerns exist around the feasibility and safety of offering curative surgery to patients treated within such pathways. The goal in this study was to evaluate the impact of a transition towards a large-scale neoadjuvant therapy program for NSCLC.

Methods

Medical charts of patients with clinical stage II and III NSCLC who underwent resection from January 2015 to December 2020 were reviewed. The primary outcome was perioperative complication rate between neoadjuvant-treated versus upfront surgery patients. Multivariable logistic regression estimated occurrence of postoperative complications and overall survival was assessed as an exploratory secondary outcome by Kaplan–Meier and Cox-regression analyses.

Results

Of the 428 patients included, 106 (24.8%) received neoadjuvant therapy and 322 (75.2%) upfront surgery. Frequency of minor and major postoperative complications was similar between groups (P = .22). Occurrence in postoperative complication was similar in both cohort (aOR = 1.31, 95% CI 0.73-2.34). Neoadjuvant therapy administration increased from 10% to 45% with a rise in targeted and immuno-therapies over time, accompanied by a reduced rate of preoperative radiation therapy use. 1-, 2-, and 5-year overall survival was higher in neoadjuvant therapy compared to upfront surgery patients (Log-Rank P = .017).

Conclusions

No significant differences in perioperative outcomes and survival were observed in resectable NSCLC patients treated by neoadjuvant therapy versus upfront surgery. Transition to neoadjuvant therapy among resectable NSCLC patients is safe and feasible from a surgical perspective.

Up to 71% of lung cancer patients admitted to the ICU are newly diagnosed. The decision to initiate cancer directed treatments in lung cancer patients admitted to the ICU remains complex. For those with identified oncogene driver mutations, targeted therapies with rapid and high response rates are attractive treatment options. However, mechanically ventilated patients face additional barriers in which enteral tube administration of oral therapies may require tablets or capsules to be crushed or opened and diluted. Data on the pharmacodynamics and pharmacokinetics of this alternative route of administration are often very limited. Here we describe the first case report of an intubated patient with newly diagnosed NSCLC who was successfully treated with opened dabrafenib capsules and crushed trametinib tablets administered through a nasogastric tube. We also provide a review of the existing literature on feeding tube administration of commonly used tyrosine kinase inhibitors in lung cancer. Tyrosine kinase inhibitors administered through feeding tubes can lead to a clinically meaningful recovery in critically ill patients.