scholarly journals First-Line Therapies for Metastatic Lung Adenocarcinoma Without a Driver Mutation

2018 ◽  
Vol 14 (9) ◽  
pp. 529-535 ◽  
Author(s):  
J. Nicholas Bodor ◽  
Vineela Kasireddy ◽  
Hossein Borghaei
Keyword(s):  
Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Driver Mutation ◽  
Driver Mutations ◽  
First Line ◽  
Histologic Subtype ◽  
First Line Therapy ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Common Histologic Subtype

Lung cancer is the leading cause of cancer-related death worldwide. The majority of these cancers are non–small-cell lung cancer, of which adenocarcinoma is the most common histologic subtype. Most patients are diagnosed at advanced stages when systemic treatment is needed. Whereas prognosis has improved for patients with targetable driver mutations, the majority of patients do not possess tumors with such molecular mutations. Platinum-based chemotherapy has traditionally been the mainstay of treatment, although in recent years immunotherapy has emerged as a treatment option and can result in robust and durable treatment responses in a subset of patients. Recent clinical trials on novel immunotherapy combinations and immunochemotherapy combinations may broaden the number of patients that may benefit from checkpoint inhibitors and elicit responses in those who otherwise may not have experienced a response to monotherapy with an immunotherapy drug. This review will outline the currently available therapies for the first-line treatment of metastatic adenocarcinoma that do not possess a driver mutation and provide a recommended approach and algorithm by which to select the best first-line therapy.

scholarly journals Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non–small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study

Lung Cancer ◽  
2018 ◽  
Vol 125 ◽  
pp. 273-281 ◽  
Author(s):  
Shirish M. Gadgeel ◽  
James P. Stevenson ◽  
Corey J. Langer ◽  
Leena Gandhi ◽  
Hossein Borghaei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Phase 1 ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Platinum Based Chemotherapy

scholarly journals Consolidation With Pembrolizumab and Nab-Paclitaxel After Induction Platinum-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Shetal A. Patel ◽  
David E. Gerber ◽  
Allison Deal ◽  
Kathe Douglas ◽  
Chad V. Pecot ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Open Label ◽  
Platinum Based Chemotherapy

BackgroundInduction with four cycles of platinum-based chemotherapy was the standard of care for metastatic non-small cell lung cancer (NSCLC) until the approval of immune checkpoint blockade (ICB) in the first-line setting. Switch maintenance therapy has shown promise in improving survival by exposing patients to novel, non-cross–resistant agents earlier in their treatment course.MethodsWe performed this open-label, three-arm, randomized phase II study (NCT02684461) to evaluate three sequences of consolidation with pembrolizumab and nab-paclitaxel in patients without progressive disease post induction chemotherapy. Consolidation was either sequential with pembrolizumab for four cycles followed by nab-paclitaxel for four cycles (P→A), nab-paclitaxel followed by pembrolizumab (A→P), or concurrent nab-paclitaxel and pembrolizumab for four cycles (AP).ResultsTwenty patients were randomized before the study was closed early due to the approval of first-line checkpoint inhibitors. We found that consolidation is feasible and well tolerated, with 30% of patients experiencing grade 3 toxicity. The median progression-free survival and OS in months (95% CI) in P→A were 10.1 (1.5–NR), 27.6 (1.7–NR); 8.4 (1.2–9.0), 12.7 (4.4–NR) in A→P; and 10.2 (5.1–NR), NR. Quality of life as measured by FACT-L improved in the majority of patients during the course of the study.ConclusionSequential and concurrent consolidation regimens are well tolerated and have encouraging overall survival in patients with metastatic NSCLC.

Phase 1/2 study of safety/efficacy using trabectedin, ipilimumab, and nivolumab as first-line treatment of advanced soft tissue sarcoma (STS).

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. TPS46-TPS46 ◽  
Author(s):  
Erlinda Maria Gordon ◽  
Victoria S. Chua-Alcala ◽  
Katherine Kim ◽  
William W. Tseng ◽  
Doris M Quon ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Phase 1 ◽  
Objective Response ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Categorical Variables ◽  
Phase 2 ◽  
First Line ◽  
First Line Therapy ◽  
Number Of Patients

TPS46 Background: Sarcoma cells are most immunogenic at the onset of cancer when the immune system can recognize and destroy them. Hence, immune checkpoint inhibitors would be most effective when given as first line therapy. Objectives: (1) To investigate the maximum tolerated dose of trabectedin, an alkylating agent, when given sequentially with ipilimumab, a CTLA4 inhibitor, and nivolumab, a PD-1 inhibitor, in advanced STS, (2) To investigate the objective response rate (ORR), progression free survival (PFS) and overall survival (OS) , and (3) To correlate PFS with PD-L1 and other biomarker expression in patients’ tumors. Methods: Forty patients ≥18 years of age with advanced STS will be enrolled. This is a phase 1/2 study using a defined dose of ipilimumab (1 mg/kg i.v. q 12 weeks), nivolumab (3 mg/kg i.v. q 2 weeks), and escalating doses of trabectedin (1.0, 1.3, 1.5 mg/m2 i.v. q 3 weeks). I. Dose Escalation Phase 1 (previously treated patients): The study will employ the standard “cohort of three” design. The maximum tolerated dose is defined as the highest safely tolerated dose, where not more than one patient experienced DLT, with the next higher dose level having at least two patients who experienced DLT. II. Expansion Phase 2 (previously untreated patients): An additional 22-28 patients will receive trabectedin at the MTD and defined doses of ipilimumab and nivolumab to assess overall safety and potential efficacy in a greater number of patients. Patients may continue treatment until significant disease progression or unacceptable toxicity occurs. Statistical Considerations: NIH CTCAE v4.03 and RECIST v1.1 will be used. Categorical variables will be summarized by the n and percent in each category. Point estimates for efficacy endpoint incidences will be accompanied by a 2-sided 95% exact binomial CI. Time to event endpoints will be summarized descriptively using the KM method. The analyses of all study objectives will be descriptive and hypothesis generating, for planning Phase 2/3 studies. Clinical trial information: NCT 03138161.

scholarly journals Chemotherapy in combination with immune checkpoint inhibitors for the first-line treatment of patients with advanced non-small cell lung cancer: A systematic review and literature-based meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20565-e20565
Author(s):  
Alfredo Addeo ◽  
Giuseppe Luigi Banna ◽  
Giulio Metro ◽  
Massimo Di Maio
Keyword(s):  
Lung Cancer ◽  
Annual Meeting ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Small Cell ◽  
Significant Heterogeneity ◽  
Small Cell Lung ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

e20565 Background: Checkpoint inhibitors plus platinum-based chemotherapy have shown superiority compared to chemotherapy alone as first-line therapy in advanced non–small cell lung carcinoma (NSCLC),To evaluate the relative benefit in term of Overall Survival (OS) and Progression-free Survival (PFS) of checkpoint inhibitors plus chemotherapy versus chemotherapy alone, overall and in subgroups defined by PDL1 expression we have performed a meta-analysis Methods: This meta-analysis searched PubMed and checked references of the selected English language articles to identify further eligible trials. Furthermore, proceedings of the main International meetings (American Society of Clinical Oncology [ASCO] annual meeting, European Society of Medical Oncology [ESMO] annual meeting, International Association for the Study of Lung Cancer [IASLC] World Conference on Lung Cancer), were searched from 2010 onwards for relevant abstracts. Data collection for this study took place from October 1 to October 24, 2018. Results: In total, 8 trials involving 4646 patients with advanced NSCLC, 3.314 (71%) and 1.332 (29%) with a non-squamous and squamous histology, respectively, were included in this meta-analysis. Four trials used atezolizumab, 3 pembrolizumab and 1 nivolumab, accounting for 2.985 (64%), 1.298 (28%) and 363 (8%) of patients, respectively. Checkpoint inhibitors plus chemotherapy were associated with prolonged OS, compared with chemotherapy in the ITT population (HR, 0.74; 95% CI, 0.64-0.87; p = 0.0002, with significant heterogeneity among trials). Within the PDL1 low group (1-49) there was a significant heterogeneity (p = 0.06) between type of drug and efficacy: the combination of chemotherapy plus pembrolizumab showed an OS benefit (HR, 0.56; 95% CI, 0.40-0.78; P< .00007) unlike the atezolizumab backbone trials (HR, 0.92; 95% CI, 0.62-1.37; P< 0.69). However, checkpoint inhibitors plus chemotherapy were associated with prolonged PFS in the ITT (HR, 0.61; 95% CI, 0.56-0.66; P < 0.00001) and across PDL1 subgroups. Conclusions: Checkpoint inhibitors plus chemotherapy compared with chemotherapy, are associated with significantly prolonged OS and PFS in first-line therapy in NSCLC. In the low PDL1 subgroups the benefit was statistically significant only in the pembrolizumab backbone trials.

scholarly journals Current advances in the treatment of lung cancer with immune checkpoint inhibitors

2021 ◽  
Vol 64 (5) ◽  
pp. 333-341
Author(s):  
Gyeong-Won Lee
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Programmed Death ◽  
Platinum Based Chemotherapy

Lung cancer is the leading cause of cancer-related deaths worldwide despite major advances in platinum-based chemotherapy and targeted therapy based on activating driving mutations. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigms in lung cancers. When used as a second-line or later treatment for non-small cell lung cancer (NSCLC), ICIs improve overall survival and exhibit better safety profiles than the standard chemotherapeutic agent, docetaxel. In front-line treatment, ICI monotherapy is significantly associated with improved clinical outcomes and fewer adverse events than platinum-based chemotherapy in patients with advanced NSCLC, who express programmed death-ligand 1 in at least 50% of all tumor cells. Moreover, ICIs combined with platinumbased chemotherapy have become the standard first-line treatment for patients with metastatic NSCLC without sensitizing mutations in the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene, regardless of programmed death-ligand 1 expression. Additionally, maintenance treatment using ICIs has also been demonstrated to improve clinical outcomes in patients with stage III unresectable NSCLC following chemoradiotherapy. Recently, the addition of ICIs to chemotherapy as the first-line treatment for extensive-stage small-cell lung cancer resulted in significantly longer overall survival and progression-free survival compared with chemotherapy alone. Although immune checkpoint inhibitors significantly improved overall survival and showed a durable response in lung cancer compared with platinum-based chemotherapy, we should foster further prospective studies to identify predictive biomarkers to determine those individuals who may benefit more from ICIs. It is also essential to overcome the development of drug resistance in patients treated with ICIs.

scholarly journals Clinical case of long-term use of atezolizumab and bevacizumab in the first-line treatment of recurrence of non-small cell lung cancer

2020 ◽  
pp. 242-247
Author(s):  
O. A. Rozonova ◽  
I. Y. Bazaeva ◽  
V. A. Gorbunova ◽  
E. V. Artamonova
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
First Line ◽  
Leading Position ◽  
Low Efficiency

Lung cancer still holds the leading position in terms of morbidity and mortality, both among men and women. The five-year survival rate for lung cancer is one of the lowest among cancers and varies from 5% to 15% for different countries. The study of new directions in the treatment of this nosology is an extremely urgent problem at the present time. The most common histological variant is non-small cell lung cancer. The presence of driver mutations (EGFR, ALK, ROS1) makes it possible to use targeted therapy in these patients. However, in the absence of driver mutations, the treatment of disseminated non-small cell lung cancer is still based on chemotherapy, which has a low efficiency, making up only about 30% in the first line of treatment. A promising approach to the treatment of this group of patients is the use of immunotherapy, in particular anti-PD-1 and anti-PD-L1 checkpoint-inhibitors. In large randomized international clinical trials, pembrolizumab and atezolizumab were shown to be effective in the first line of treatment, and nivolumab in the second line of treatment. Moreover, according to meta-analyses on the effectiveness and safety of immunotherapy, PD-L1 inhibitors (atezolizumab, avelumab, and durvalumab) have a lower toxicity profile compared to PD-1 inhibitors (pembrolizumab and nivolumab). This article presents a clinical observation of effective treatment of a patient with disseminated non-squamous non-small cell lung cancer with a combination of atezolizumab with bevacizumab and chemotherapy. The partial effect of treatment achieved in this patient is maintained for 3 years without the unacceptable toxicity.

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