scholarly journals Maintenance Chemotherapy for Advanced Non–Small-Cell Lung Cancer: New Life for an Old Idea

2013 ◽  
Vol 31 (8) ◽  
pp. 1009-1020 ◽  
Author(s):  
David E. Gerber ◽  
Joan H. Schiller
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Maintenance Chemotherapy ◽  
Small Cell Lung ◽  
First Line ◽  
Continuation Maintenance ◽  
Line Chemotherapy

Although well established for the treatment of certain hematologic malignancies, maintenance therapy has only recently become a treatment paradigm for advanced non–small-cell lung cancer. Maintenance therapy, which is designed to prolong a clinically favorable state after completion of a predefined number of induction chemotherapy cycles, has two principal paradigms. Continuation maintenance therapy entails the ongoing administration of a component of the initial chemotherapy regimen, generally the nonplatinum cytotoxic drug or a molecular targeted agent. With switch maintenance (also known as sequential therapy), a new and potentially non–cross-resistant agent is introduced immediately on completion of first-line chemotherapy. Potential rationales for maintenance therapy include increased exposure to effective therapies, decreasing chemotherapy resistance, optimizing efficacy of chemotherapeutic agents, antiangiogenic effects, and altering antitumor immunity. To date, switch maintenance therapy strategies with pemetrexed and erlotinib have demonstrated improved overall survival, resulting in US Food and Drug Administration approval for this indication. Recently, continuation maintenance with pemetrexed was found to prolong overall survival as well. Factors predicting benefit from maintenance chemotherapy include the degree of response to first-line therapy, performance status, the likelihood of receiving further therapy at the time of progression, and tumor histology and molecular characteristics. Several aspects of maintenance therapy have raised considerable debate in the thoracic oncology community, including clinical trial end points, the prevalence of second-line chemotherapy administration, the role of treatment-free intervals, quality of life, economic considerations, and whether progression-free survival is a worthy therapeutic goal in this disease setting.

scholarly journals Nivolumab and Ipilimumab as Maintenance Therapy in Extensive-Disease Small-Cell Lung Cancer: CheckMate 451

2021 ◽  
Vol 39 (12) ◽  
pp. 1349-1359 ◽  
Author(s):  
Taofeek K. Owonikoko ◽  
Keunchil Park ◽  
Ramaswamy Govindan ◽  
Neal Ready ◽  
Martin Reck ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
First Line ◽  
Extensive Disease ◽  
Line Chemotherapy

PURPOSE In extensive-disease small-cell lung cancer (ED-SCLC), response rates to first-line platinum-based chemotherapy are robust, but responses lack durability. CheckMate 451, a double-blind phase III trial, evaluated nivolumab plus ipilimumab and nivolumab monotherapy as maintenance therapy following first-line chemotherapy for ED-SCLC. METHODS Patients with ED-SCLC, Eastern Cooperative Oncology Group performance status 0-1, and no progression after ≤ 4 cycles of first-line chemotherapy were randomly assigned (1:1:1) to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks for 12 weeks followed by nivolumab 240 mg once every 2 weeks, nivolumab 240 mg once every 2 weeks, or placebo for ≤ 2 years or until progression or unacceptable toxicity. Primary end point was overall survival (OS) with nivolumab plus ipilimumab versus placebo. Secondary end points were hierarchically tested. RESULTS Overall, 834 patients were randomly assigned. The minimum follow-up was 8.9 months. OS was not significantly prolonged with nivolumab plus ipilimumab versus placebo (hazard ratio [HR], 0.92; 95% CI, 0.75 to 1.12; P = .37; median, 9.2 v 9.6 months). The HR for OS with nivolumab versus placebo was 0.84 (95% CI, 0.69 to 1.02); the median OS for nivolumab was 10.4 months. Progression-free survival HRs versus placebo were 0.72 for nivolumab plus ipilimumab (95% CI, 0.60 to 0.87) and 0.67 for nivolumab (95% CI, 0.56 to 0.81). A trend toward OS benefit with nivolumab plus ipilimumab was observed in patients with tumor mutational burden ≥ 13 mutations per megabase. Rates of grade 3-4 treatment-related adverse events were nivolumab plus ipilimumab (52.2%), nivolumab (11.5%), and placebo (8.4%). CONCLUSION Maintenance therapy with nivolumab plus ipilimumab did not prolong OS for patients with ED-SCLC who did not progress on first-line chemotherapy. There were no new safety signals.

PARAMOUNT: Final Overall Survival Results of the Phase III Study of Maintenance Pemetrexed Versus Placebo Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non–Small-Cell Lung Cancer

2013 ◽  
Vol 31 (23) ◽  
pp. 2895-2902 ◽  
Author(s):  
Luis G. Paz-Ares ◽  
Filippo de Marinis ◽  
Mircea Dediu ◽  
Michael Thomas ◽  
Jean-Louis Pujol ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Performance Status ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Continuation Maintenance

Purpose In the phase III PARAMOUNT trial, pemetrexed continuation maintenance therapy reduced the risk of disease progression versus placebo (hazard ratio [HR], 0.62; 95% CI, 0.49 to 0.79; P < .001). Here we report final overall survival (OS) and updated safety data. Patients and Methods In all, 939 patients with advanced nonsquamous non–small-cell lung cancer (NSCLC) received four cycles of pemetrexed-cisplatin induction therapy; then, 539 patients with no disease progression and Eastern Cooperative Oncology Group performance status 0 or 1 were randomly assigned (2:1) to maintenance pemetrexed (500 mg/m2 on day 1 of 21-day cycles; n = 359) or placebo (n = 180). Log-rank test compared OS between arms as measured from random assignment (α = .0498). Results The mean number of maintenance cycles was 7.9 (range, one to 44) for pemetrexed and 5.0 (range, one to 38) for placebo. After 397 deaths (pemetrexed, 71%; placebo, 78%) and a median follow-up of 24.3 months for alive patients (95% CI, 23.2 to 25.1 months), pemetrexed therapy resulted in a statistically significant 22% reduction in the risk of death (HR, 0.78; 95% CI, 0.64 to 0.96; P = .0195; median OS: pemetrexed, 13.9 months; placebo, 11.0 months). Survival on pemetrexed was consistently improved for all patient subgroups, including induction response: complete/partial responders (n = 234) OS HR, 0.81; 95% CI, 0.59 to 1.11 and stable disease (n = 285) OS HR, 0.76; 95% CI, 0.57 to 1.01). Postdiscontinuation therapy use was similar: pemetrexed, 64%; placebo, 72%. No new safety findings emerged. Drug-related grade 3 to 4 anemia, fatigue, and neutropenia were significantly higher in pemetrexed-treated patients. Conclusion Pemetrexed continuation maintenance therapy is well-tolerated and offers superior OS compared with placebo, further demonstrating that it is an efficacious treatment strategy for patients with advanced nonsquamous NSCLC and good performance status who did not progress during pemetrexed-cisplatin induction therapy.

scholarly journals Strategies for Prolonged Therapy in Patients With Advanced Non–Small-Cell Lung Cancer

2010 ◽  
Vol 28 (34) ◽  
pp. 5116-5123 ◽  
Author(s):  
Panos Fidias ◽  
Silvia Novello
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Continuation Maintenance

Purpose A key challenge in the treatment of advanced non–small-cell lung cancer (NSCLC) is improving outcomes for patients who have achieved at least stable disease after standard first-line therapy. Although current guidelines recommend a maximum of six cycles of first-line therapy, even in responding patients, recent trials have shown benefit with maintenance therapy. Methods We reviewed the English literature for randomized controlled trials on prolonged therapy for NSCLC conducted between January 1999 and January 2010. The search was supplemented by a review of abstracts presented at the American Society of Clinical Oncology annual meetings (2004 to 2010), the World Lung Cancer Conference (2007 to 2009), and the 2009 Joint European CanCer Organisation-European Society for Medical Oncology conference. Results Several alternative strategies for prolongation of chemotherapy have been tested: these can be broadly categorized as continuation (prolongation of the first-line regimen until disease progression, unacceptable toxicity, or administration of a predefined greater number of treatment cycles), switch-maintenance (administration of an active agent immediately after completion of the initial course of chemotherapy), and continuation-maintenance (ongoing administration of a lower intensity version of the first-line chemotherapy regimen). These approaches differ from traditional second line, which is defined as treatment administered after documented clinical progression subsequent to first-line therapy. Conclusion There are no data to support continuation chemotherapy in advanced NSCLC. Switch-maintenance trials with erlotinib and pemetrexed have demonstrated an improvement in overall survival. Thus far, continuation-maintenance has shown an improvement in progression-free survival, without an overall survival advantage.

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