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Rapidly changing treatment algorithms for metastatic nonsquamous non-small-cell lung cancer.

ABSTRACT: Background:The treatment paradigm for metastatic nonsquamous non-small-cell lung cancer (nsclc) continues to change. Algorithms published only 6 months ago are outdated today and are dramatically different from those published a few years ago. New driver mutations continue to be identified, and the development of therapies to inhibit oncogenic addiction is ongoing. Patient survival is improving as treatments become more personalized and effective. Methods:This review looks at the outcomes of recent trials and discusses treatment options for patients with metastatic nsclc of nonsquamous histology. Algorithms continue to change quickly, and an attempt is made to keep the paradigm current and applicable into the near future. Results:Treatment algorithms for nsclc tumours with EGFR mutations, ALK rearrangements, and ROS1 rearrangements, and for wild-type tumours are presented. A future algorithm based on new immunotherapy data is proposed. Conclusions:The treatment algorithm for EGFR mutation is changing with the proven efficacy of osimertinib for the acquired T790M mutation. All patients taking first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors must be tested. The treatment algorithm for ALK rearrangement has changed with the proven superiority of alectinib compared with crizotinib in the first-line setting. The approval of crizotinib for ROS1 rearrangements now means that patients also must be tested for that mutation. The biomarker for checkpoint inhibitors continues to be PD-L1 by immunohistochemistry stain, but whether testing will be necessary for patient selection if chemotherapy combinations are implemented will be determined soon.

SUBMITTER: Melosky B

PROVIDER: S-EPMC6001773 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Rapidly changing treatment algorithms for metastatic nonsquamous non-small-cell lung cancer.

Melosky B B

Current oncology (Toronto, Ont.) 20180613 Suppl 1

<h4>Background</h4>The treatment paradigm for metastatic nonsquamous non-small-cell lung cancer (nsclc) continues to change. Algorithms published only 6 months ago are outdated today and are dramatically different from those published a few years ago. New driver mutations continue to be identified, and the development of therapies to inhibit oncogenic addiction is ongoing. Patient survival is improving as treatments become more personalized and effective.<h4>Methods</h4>This review looks at the ...[more]

PMID: 29910649

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Project description:ImportanceImmune checkpoint inhibitor combination therapy has recently become the standard of care for first-line treatment of metastatic nonsquamous non-small cell lung cancer. The implications of these first-line treatments are considerable, given the potential population of patients eligible to receive them and their high cost.ObjectiveTo evaluate the cost-effectiveness of adding atezolizumab to bevacizumab, carboplatin, and paclitaxel as a first-line treatment strategy for patients with metastatic nonsquamous non-small cell lung cancer in the United States.Design, setting, and participantsIn this economic evaluation, a primary microsimulation model was developed to assess atezolizumab combination vs bevacizumab, carboplatin, and paclitaxel alone in the first line (base case 1). A secondary model was developed to assess these treatments along with pembrolizumab combination and platinum doublet chemotherapy (base case 2). Treatment strategies and other simulated conditions were based on those from the IMpower150 and KEYNOTE-189 clinical trials. The study perspective was the US health care sector. One million patients with metastatic nonsquamous non-small cell lung cancer were simulated for each treatment group. This study was performed from February 2019 through May 2019.Main outcomes and measuresIncremental cost-effectiveness ratios were compared with a willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY).ResultsIn base case 1, in which 1 million patients were simulated, treating with bevacizumab, carboplatin, and paclitaxel in the first line was associated with a mean cost of $112 551 (95% CI, $112 450-$112 653) and a mean survival of 1.48 QALYs (95% CI, 1.47-1.48 QALYs) per patient. Atezolizumab plus bevacizumab, carboplatin, and paclitaxel was associated with a mean cost of $244 166 (95% CI, $243 864-$244 468) and a mean survival of 2.13 QALYs (95% CI, 2.12-2.13 QALYs) per patient, for an estimated incremental cost-effectiveness ratio of $201 676 per QALY (95% CI, $198 105-$205 355 per QALY). In base case 2, in which 1 million patients were simulated, pembrolizumab combination therapy was associated with a mean cost of $226 282 (95% CI, $226 007-$226 557) and a mean survival of 2.45 QALYs (95% CI, 2.44-2.46 QALYs) per patient. Pembrolizumab combination dominated atezolizumab plus bevacizumab, carboplatin, and paclitaxel, leading to an incremental cost-effectiveness ratio of $116 698 per QALY (95% CI, $115 088-$118 342 per QALY) between pembrolizumab combination and bevacizumab, carboplatin, and paclitaxel. Atezolizumab combination was not cost-effective at a willingness-to-pay threshold of $100 000 per QALY.Conclusions and relevanceIn this simulated model economic analysis, atezolizumab combination was not cost-effective compared with bevacizumab, carboplatin, and paclitaxel and provided suboptimal incremental benefit compared with cost vs pembrolizumab combination for first-line treatment. Although atezolizumab combination therapy provides clinical benefits, price reductions may be necessary for this treatment strategy to become cost-effective.

Project description:Objective: To investigate the cost-effectiveness of adding Chinese-developed anti-PD-1 antibody tislelizumab to first-line pemetrexed-platinum chemotherapy in (1) a study population of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (nsqNSCLC) and without known sensitizing EGFR mutations or ALK rearrangements and (2) its subgroups from the perspective of Chinese healthcare system. Material and Methods: Separate Markov models were constructed for the entire study population and its subgroups; 10,000 patients with locally advanced or metastatic nsqNSCLC and without driver gene mutations were simulated in the first-line tislelizumab plus pemetrexed-platinum (TPP) arm and first-line pemetrexed-platinum (PP) arm, respectively. Transition probabilities were extracted from the RATIONALE 304 trial. Public health state utilities and costs were obtained from published literature, public national databases, and local general hospitals. The main outputs were incremental cost-effectiveness ratios (ICERs). The ICERs were compared to a willingness-to-pay threshold of $35,663 per quality-adjusted life-years (QALYs) to determine the cost-effective treatment. Sensitivity analyses were employed to assess the uncertainty in the model. Results: For the entire patient population, first-line TPP versus PP use increased the effectiveness by 0.99 QALYs and healthcare costs by $28,749, resulting in an ICER of $28,749/QALY that was lower than the prespecified WTP threshold. For patient subgroups, first-line TPP conferred the greatest survival benefit in patients with PD-L1 expression ≥50%, followed by patients with liver metastasis and those who are current or former smokers. Overall, the ICERs for the first-line TPP versus PP ranged from $27,018/QALYs to $33,074/QALYs, which were consistently below the WTP threshold. Conclusion: For Chinese patients with locally advanced or metastatic nsqNSCLC who had no known sensitizing EGFR mutations or ALK rearrangements, adding the Chinese-developed anti-PD-1 antibody tislelizumab to the first-line pemetrexed-platinum chemotherapy was cost-effective regardless of their baseline characteristics.

Project description:Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity.In this randomized, open-label, international phase 3 study, we assigned patients with nonsquamous non-small-cell lung cancer (NSCLC) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival.Overall survival was longer with nivolumab than with docetaxel. The median overall survival was 12.2 months (95% confidence interval [CI], 9.7 to 15.0) among 292 patients in the nivolumab group and 9.4 months (95% CI, 8.1 to 10.7) among 290 patients in the docetaxel group (hazard ratio for death, 0.73; 96% CI, 0.59 to 0.89; P=0.002). At 1 year, the overall survival rate was 51% (95% CI, 45 to 56) with nivolumab versus 39% (95% CI, 33 to 45) with docetaxel. With additional follow-up, the overall survival rate at 18 months was 39% (95% CI, 34 to 45) with nivolumab versus 23% (95% CI, 19 to 28) with docetaxel. The response rate was 19% with nivolumab versus 12% with docetaxel (P=0.02). Although progression-free survival did not favor nivolumab over docetaxel (median, 2.3 months and 4.2 months, respectively), the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel (19% and 8%, respectively). Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression (?1%, ?5%, and ?10%) of the PD-1 ligand. Treatment-related adverse events of grade 3 or 4 were reported in 10% of the patients in the nivolumab group, as compared with 54% of those in the docetaxel group.Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy, overall survival was longer with nivolumab than with docetaxel. (Funded by Bristol-Myers Squibb; CheckMate 057 ClinicalTrials.gov number, NCT01673867.).

Dataset Information

Rapidly changing treatment algorithms for metastatic nonsquamous non-small-cell lung cancer.

Publications

Rapidly changing treatment algorithms for metastatic nonsquamous non-small-cell lung cancer.

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