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Thoracic Cancer Apr 2024Pemetrexed (PEM) is the primary chemotherapy for non-small cell lung cancer (NSCLC), showing potential for long-term disease stability in certain cases. However, studies...
BACKGROUND
Pemetrexed (PEM) is the primary chemotherapy for non-small cell lung cancer (NSCLC), showing potential for long-term disease stability in certain cases. However, studies examining disease control with PEM therapy are lacking. This study aimed to pinpoint clinical traits in patients with NSCLC responding well to PEM therapy, predict factors influencing disease control, and suggest optimal treatment approaches.
METHODS
A retrospective analysis of patients with NSCLC treated with PEM was performed to compare patients who achieved disease control after treatment with those who did not.
RESULTS
Of 73 patients, 56 (76.7%) achieved disease control with PEM therapy. In the disease control group, a significantly higher proportion of patients exhibited good performance status (PS) and received PEM doses without reduction after the second cycle. Multivariate analysis identified bevacizumab (Bev) noncompliance, PEM dose reduction, and thyroid transcription factor-1 (TTF-1) negativity as significant independent risk factors for disease progression during PEM therapy. Additionally, overall survival was significantly longer in the disease control group (p < 0.001).
CONCLUSIONS
Our findings indicated that maintaining the dose of PEM after the second treatment cycle in patients with NSCLC, along with concurrent use of Bev and the presence of TTF-1 positivity, could enhance disease control rates and extend survival.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Pemetrexed; Male; Female; Lung Neoplasms; Aged; Middle Aged; Retrospective Studies; Aged, 80 and over; Adult
PubMed: 38485287
DOI: 10.1111/1759-7714.15286 -
Lung Cancer (Amsterdam, Netherlands) Apr 2024For patients with unresectable, stage III non-small-cell lung cancer (NSCLC), current standard of care is concurrent chemoradiotherapy (cCRT) followed by consolidation...
INTRODUCTION
For patients with unresectable, stage III non-small-cell lung cancer (NSCLC), current standard of care is concurrent chemoradiotherapy (cCRT) followed by consolidation durvalumab. However, earlier initiation of durvalumab simultaneously with cCRT may increase antitumor activity relative to initiation after cCRT. The phase 1 CLOVER study (NCT03509012) evaluated durvalumab combined with cCRT in patients with advanced solid tumors; we report findings from the NSCLC cohort.
METHODS
CLOVER comprised a dose-limiting toxicity (DLT) assessment part, followed by an expansion part. In the NSCLC cohort, patients with previously untreated, unresectable, stage III NSCLC were enrolled in three treatment arms: durvalumab every 4 weeks (Q4W) + cisplatin + etoposide + radiotherapy (Arm 1); durvalumab Q4W + carboplatin + paclitaxel + radiotherapy (Arm 2); or durvalumab Q4W + carboplatin or cisplatin + pemetrexed + radiotherapy (non-squamous histology only; Arm 3). Patients received durvalumab until disease progression or unacceptable toxicity. The primary endpoint was safety and tolerability.
RESULTS
Sixty-four patients were enrolled: 21, 22, and 21 in Arms 1, 2, and 3, respectively. One patient in Arm 1 had DLT (grade 3 aspartate aminotransferase increase and grade 4 alanine aminotransferase increase); no DLTs were observed in Arms 2 or 3. Grade 3/4 adverse events occurred in 76.6 % of patients overall; the most common were neutropenia (51.6 %), leukopenia (20.3 %), and anemia (17.2 %). In a post-hoc analysis, 7.8 % of patients had grade 3 pneumonitis/radiation pneumonitis (grouped term) events. Overall, the objective response rate was 60.9 % (95 % confidence interval [CI], 47.9-72.9); median duration of response was 15.8 months (95 % CI, 9.0-not estimable [NE]). Median progression-free survival was 13.4 months (95 % CI, 8.8-20.1) and median overall survival was not reached (95 % CI, 21.9-NE).
CONCLUSION
Durvalumab in combination with cCRT was well tolerated, with a manageable safety profile and showed encouraging antitumor activity in patients with unresectable, stage III NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Cisplatin; Carboplatin; Paclitaxel; Chemoradiotherapy; Neoplasm Staging; Antibodies, Monoclonal
PubMed: 38471416
DOI: 10.1016/j.lungcan.2024.107530 -
Journal of Neurosurgery. Case Lessons Mar 2024Systemic therapy for cancer treatment has improved, and therapeutic options for intracranial lesions are increasing. Combinations of treatment modalities are required in...
BACKGROUND
Systemic therapy for cancer treatment has improved, and therapeutic options for intracranial lesions are increasing. Combinations of treatment modalities are required in certain difficult cases. Gamma Knife radiosurgery (GKS) is effective for the treatment of brain metastases, especially for lesions that are inoperable because of their anatomical or functional location.
OBSERVATIONS
The authors report a case of brain metastases in anaplastic lymphoma kinase (ALK)-positive lung adenocarcinoma initially treated with GKS followed by the combination of repeat GKS and ALK tyrosine kinase inhibitors (ALK-TKIs) for tumor recurrence. During the clinical course, acquired resistance to ALK-TKIs due to the long exposure period was suspected. After a great deal of thought and discussion with the oncologist responsible for the treatment of the pulmonary lesions, the authors successfully controlled the lesion for the next 17 months by salvage pemetrexed administration.
LESSONS
This is the first report on the effectiveness of pemetrexed for recurrent brain metastasis from ALK-positive lung adenocarcinoma resistant to both radiosurgery and ALK inhibitors. Salvage pemetrexed showed a favorable therapeutic effect in this specific case.
PubMed: 38467041
DOI: 10.3171/CASE243 -
Respirology Case Reports Mar 2024A 66-year-old woman was found to have abnormal shadows on a chest radiograph at a previous hospital 4 years ago, which led to a diagnosis of lung adenocarcinoma,...
A 66-year-old woman was found to have abnormal shadows on a chest radiograph at a previous hospital 4 years ago, which led to a diagnosis of lung adenocarcinoma, cT2aN1M1b stage IVA. First-line treatment included carboplatin and paclitaxel plus thoracic radiotherapy and stereotactic radiation therapy for brain metastases. The patient later underwent second-line pemetrexed treatment, followed by third-line nivolumab, fourth-line docetaxel and bevacizumab, fifth-line tegafur-gimeracil-oteracil, and sixth-line gemcitabine. Two years ago, after observing an increase in the primary lesion and carcinoembryonic antigen levels (104.0 ng/mL), a computed tomography-guided biopsy was performed from the primary site of lung cancer. A cancer genomic profiling test (FoundationOne® CDx cancer genome profile) revealed a breast cancer susceptibility (BRCA) 2 gene mutation. Therefore, she started taking olaparib. The treatment led to stable disease for approximately 2 years.
PubMed: 38455501
DOI: 10.1002/rcr2.1317 -
JCO Precision Oncology Mar 2024Timely biomarker testing remains out of reach for many patients with advanced non-small-cell lung cancer (aNSCLC). Here, we studied the quality-of-care implications of...
PURPOSE
Timely biomarker testing remains out of reach for many patients with advanced non-small-cell lung cancer (aNSCLC). Here, we studied the quality-of-care implications of closing the gap in timely receipt of comprehensive genomic profiling (CGP) to inform first-line (1L) decisions.
METHODS
Using a real-world clinicogenomic database, we studied testing and 1L treatment patterns in aNSCLC after the approval of pembrolizumab in combination with pemetrexed and carboplatin (May 10, 2017). To estimate the association of timely CGP results with therapy selection and patient outcomes, we identified patients with no previous genomic testing beyond PD-L1 immunohistochemistry and dichotomized patients by whether CGP results were available before or after 1L therapy initiation.
RESULTS
In total, 2,694 patients were included in the 1L therapy decision impact assessment. Timely CGP increased matched targeted therapy use by 14 percentage points (17% with CGP 2.8% without) and precision immune checkpoint inhibitor (ICPI) use by 14 percentage points (18% with CGP 3.9% without). Receipt of timely CGP resulted in an estimated 31 percentage point decrease in ICPI use among -positive patients at an expected per-patient reduction in ineffective ICPI therapy cost of $13,659.37 with timely CGP to inform 1L treatment selection. Patient benefit of CGP extended to real-world time to therapy discontinuation (median time to therapy discontinuation: 3.9 10 months [hazard ratio, HR, 0.54 [95% CI, 0.42 to 0.70]; = 1.9E-06; adjusted hazard ratio [aHR], 0.50 [95% CI, 0.38 to 0.67]; = 2.0E-06) in 1L driver-positive patients. This effect was not significant for real-world overall survival (median overall survival: 32 29 months [HR, 1.2 [95% CI, 0.84 to 1.67]; = .33; aHR, 1.4 [95% CI, 0.92 to 1.99]; = .12).
CONCLUSION
Timely CGP is associated with the quality of patient care as measured by 1L matched targeted therapy use, time to therapy discontinuation, and avoidance of ineffective, costly ICPIs.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Protein-Tyrosine Kinases; Precision Medicine; Proto-Oncogene Proteins; Genomics
PubMed: 38452312
DOI: 10.1200/PO.23.00292 -
Lung Cancer (Amsterdam, Netherlands) Apr 2024STK11/LKB1 mutations have been associated with primary resistance to PD-1 axis inhibitors and poor prognosis in advanced KRAS-mutant lung adenocarcinoma. This study...
BACKGROUND
STK11/LKB1 mutations have been associated with primary resistance to PD-1 axis inhibitors and poor prognosis in advanced KRAS-mutant lung adenocarcinoma. This study aimed to assess the prognostic significance of STK11/LKB1 alterations in localized non-squamous non-small cell lung carcinoma (non-sq NSCLC).
PATIENTS AND METHODS
Surgical samples from patients undergoing complete resection for stage IIa, IIb, or IIIa (N2 excluded) non-sq NSCLC in the randomized adjuvant phase II trial (NCT00775385 IFCT-1801 TASTE trial) were examined. Patients received either standard chemotherapy (Pemetrexed Cisplatin) or personalized treatment based on EGFR mutation (Erlotinib) and ERCC1 expression. Tumor molecular profiles were analyzed using targeted NGS and correlated with overall survival (OS) and disease-free survival (DFS), adjusting for relevant clinical variables. Additionally, interactions between treatment groups and molecular alterations on OS, PD-L1 expression, and tumor-circulating DNA in post-operative plasma samples were evaluated.
RESULTS
Among 134 patients (predominantly male smokers with adenocarcinoma), KRAS mutations were associated with shorter DFS (HR: 1.95, 95 % CI: 1.1-3.4, p = 0.02) and OS (HR: 2.32, 95 % CI: 1.2-4.6, p = 0.014). Isolated STK11/LKB1 mutations (n = 18) did not significantly impact DFS or OS. However, within KRAS-mutated samples (n = 53), patients with concurrent STK11/LKB1 mutations (n = 10) exhibited significantly shorter DFS (HR: 3.85, CI: 1.5-10.2, p = 0.006) and a trend towards shorter OS (HR: 1.80, CI: 0.6-5.3, p = 0.28). No associations were found between PD-L1 expression, other gene mutations, progression-free survival (PFS), or OS.
CONCLUSION
This analysis reinforces KRAS mutations as predictive factors for relapse and poor survival in localized non-sq NSCLC. Furthermore, the presence of concomitant STK11/LKB1 mutations exacerbated the prognosis within the KRAS-mutated subset. These findings emphasize the clinical relevance of these molecular markers and their potential impact on treatment strategies in non-sq NSCLC.
Topics: Female; Humans; Male; Adenocarcinoma of Lung; AMP-Activated Protein Kinase Kinases; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Mutation; Neoplasm Recurrence, Local; Prognosis; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins p21(ras)
PubMed: 38428265
DOI: 10.1016/j.lungcan.2024.107508 -
Oncology Letters Apr 2024The present report described the case of a 74-year-old male patient with asbestos exposure whose chest computed tomography revealed a right lower lobe nodule and right...
The present report described the case of a 74-year-old male patient with asbestos exposure whose chest computed tomography revealed a right lower lobe nodule and right pleural effusion. Pleural biopsy led to the diagnosis of epithelial malignant pleural mesothelioma (cT2N0M0, stage IB). Combination therapy with cisplatin + pemetrexed led to the complete remission of malignant pleural mesothelioma; however, the right lower lobe nodule grew in size over time. The patient was subsequently diagnosed with lung adenocarcinoma (cT1aN0M0, stage IA1) by computed tomography-guided biopsy performed 18 months after chemotherapy initiation and achieved remission of lung adenocarcinoma with stereotactic radiotherapy. The patient was alive without recurrence at the 12-month follow-up. The present case illustrated that multiple active regimens are currently available for malignant pleural mesothelioma and lung cancer that can aid in the treatment of complex cases.
PubMed: 38426158
DOI: 10.3892/ol.2024.14288 -
Lung Cancer (Amsterdam, Netherlands) Apr 2024First-line pembrolizumab plus chemotherapy has shown clinical benefit in patients with metastatic non-small cell lung cancer (NSCLC) regardless of tissue tumor...
BACKGROUND
First-line pembrolizumab plus chemotherapy has shown clinical benefit in patients with metastatic non-small cell lung cancer (NSCLC) regardless of tissue tumor mutational burden (tTMB) status. Blood tumor mutational burden (bTMB), assessed using plasma-derived circulating tumor DNA (ctDNA), may be a surrogate for tTMB. The KEYNOTE-782 study evaluated the correlation of bTMB with the efficacy of first-line pembrolizumab plus chemotherapy in NSCLC.
METHODS
Previously untreated patients with stage IV nonsquamous NSCLC received pembrolizumab 200 mg plus pemetrexed 500 mg/m and investigator's choice of carboplatin area under the curve 5 mg/mL/min or cisplatin 75 mg/m for 4 cycles, then pembrolizumab plus pemetrexed for ≤31 additional cycles every 3 weeks. Study objectives were to evaluate the association of baseline bTMB with objective response rate (ORR) (RECIST v1.1 by investigator assessment; primary), progression-free survival (PFS; RECIST v1.1 by investigator assessment), overall survival (OS), and adverse events (AEs; all secondary). A next-generation sequencing assay (GRAIL LLC) with a ctDNA panel that included lung cancer-associated and immune gene targets was used to measure bTMB.
RESULTS
117 patients were enrolled; median time from first dose to data cutoff was 19.3 months (range, 1.0-35.5). ORR was 40.2 % (95 % CI 31.2-49.6 %), median PFS was 7.2 months (95 % CI 5.6-9.8) and median OS was 18.1 months (95 % CI 13.5-25.6). Treatment-related AEs occurred in 113 patients (96.6 %; grade 3-5, n = 56 [47.9 %]). Of patients with evaluable bTMB (n = 101), the area under the receiver operating characteristics curve for continuous bTMB to discriminate response was 0.47 (95 % CI 0.36-0.59). Baseline bTMB was not associated with PFS or OS (posterior probabilities of positive association: 16.8 % and 7.8 %, respectively).
CONCLUSIONS
AEs were consistent with the established safety profile of first-line pembrolizumab plus chemotherapy in NSCLC. Baseline bTMB did not show evidence of an association with efficacy.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Pemetrexed; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38422883
DOI: 10.1016/j.lungcan.2024.107506 -
In Vivo (Athens, Greece) 2024Recent lung cancer treatments include an immune checkpoint inhibitor (ICI) pembrolizumab, platinum-based agents, plus an additional cytotoxic anticancer agent....
BACKGROUND/AIM
Recent lung cancer treatments include an immune checkpoint inhibitor (ICI) pembrolizumab, platinum-based agents, plus an additional cytotoxic anticancer agent. Nutritional indices, such as the geriatric nutritional risk index (GNRI) and the prognostic nutritional index (PNI), are known to correlate with the prognosis of cancer chemotherapy. Several previous studies have investigated the relationship between PNI and treatment response in non-small cell lung cancer patients, reporting significantly increased OS and PFS in the high PNI group before treatment. However, the relationship between the three-drug combination and GNRI/PNI is unclear. The current study aimed to investigate the association of nutritional indices with duration of treatment success and occurrence of side effects in triple therapy.
PATIENTS AND METHODS
Seventy-two patients with non-small cell lung cancer, treated with combination of carboplatin, pemetrexed, and pembrolizumab from November 2019 to September 30, 2022, were classified into two groups (High and Low) for GNRI and PNI, and a retrospective study was performed.
RESULTS
In terms of time-to-treatment-failure (TTF), univariate and multivariate Cox proportional hazards regression analysis showed the Low-PNI group to have significantly shorter TTF than the High-PNI group (p=0.006); multivariate analysis results also showed PNI as a factor affecting TTF (HR=2.791, 95%CI=1.362-5.721, p=0.005). On the other hand, GNRI was not shown to be a factor affecting TTF.
CONCLUSION
PNI at the start of treatment was an independent prognostic factor affecting treatment success time (TTF) in non-small cell lung cancer patients receiving triple therapy. However, PNI was not shown to be a prognostic predictor of irAE development.
Topics: Humans; Aged; Lung Neoplasms; Nutrition Assessment; Carcinoma, Non-Small-Cell Lung; Retrospective Studies; Prognosis; Antineoplastic Agents
PubMed: 38418111
DOI: 10.21873/invivo.13512 -
Journal of Thoracic Disease Jan 2024So far, the treatment options for most advanced non-small cell lung cancer (NSCLC) with brain metastasis have been limited. Apatinib, an oral tyrosine kinase inhibitor...
BACKGROUND
So far, the treatment options for most advanced non-small cell lung cancer (NSCLC) with brain metastasis have been limited. Apatinib, an oral tyrosine kinase inhibitor (TKI) with anti-angiogenesis properties, has been approved for advanced gastric cancer in China. Clinical studies have demonstrated that apatinib also displays anticancer effects against several other human cancers, including NSCLC. We have observed that apatinib combined with pemetrexed or docetaxel shows promising efficiency for advanced NSCLC patients who have previously undergone two or more lines of treatment, we would like to further perform a retrospective efficiency analysis of apatinib combined with pemetrexed or docetaxel in advanced NSCLC patients with multiple brain metastasis in this study.
METHODS
A total of 35 patients, between 18 and 70 years old, who were clinically and pathologically confirmed as having advanced NSCLC were included in this study. All of the included patients had accepted two or more lines of treatment. These patients received apatinib combined with pemetrexed or docetaxel between January 2014 and November 2020 in Hubei Cancer Hospital.
RESULTS
The results showed that apatinib combined with pemetrexed or docetaxel could effectively delay the disease progression of brain metastasis in advanced NSCLC, with an approximate overall response rate (ORR) for measurable and non-measurable lesions of 10% and 15%, respectively. The disease control rate (DCR) for intracranial lesions was 66%, the median progression-free survival (PFS) was 4.0 months, and the median overall survival (OS) was 9.0 months. The most common treatment-related toxicities, such as fatigue, decreased appetite, and hand-foot syndrome (HFS), were either mild or moderate and tolerable.
CONCLUSIONS
Since there is currently no effective treatment for patients with advanced NSCLC patients with brain metastasis who have already undergone two or more lines of treatment, the promising efficiency of apatinib combined with pemetrexed or docetaxel would be of great significance for these heavily ill patients. The real therapeutic value of this method against brain metastasis needs to be confirmed by large, random, and prospective clinical trials in the future.
PubMed: 38410538
DOI: 10.21037/jtd-23-1860