Despite remarkable treatment advancements in patients with advanced non–small cell lung cancer (NSCLC), recurrence rates for those with resectable, early-stage disease remains high. Immune checkpoint inhibitors and targeted therapies are 2 promising treatment modalities that may improve survival outcomes for patients with resected NSCLC when moved from the advanced stage to the curable setting. There are many clinical studies that have evaluated or are currently evaluating immunotherapy or targeted therapy in the perioperative setting, and recent trials such as CheckMate 816, ADAURA, and IMpower010 have led to new approvals and demonstrated the promise of this approach. This review discusses recent and ongoing neoadjuvant and adjuvant systemic therapy trials in NSCLC, and where the field may be going in the near future.
The past decade has seen two major changes leading to marked improvements in the outcomes of patients with advanced NSCLC. First, the testing for biomarkers such as EGFR mutations and treatment with highly effective tyrosine kinase inhibitors (TKIs) such as osimertinib, 1 and second, the use of immune checkpoint inhibitors (CPIs) alone 2 or with chemotherapy in patients without EGFR or ALK alterations. 3,4 Nevertheless, the utility of CPIs in patients with EGFR mutations (and other driver oncogenes) remains controversial, and most trials using immuno-oncology (IO) have excluded these patients, 4 making it very hard to know how best to manage these patients after progression on TKIs.Results from the IMpower150 trial led to the approval by the U.S. Food and Drug Administration of the ABCP (atezolizumab, bevacizumab, carboplatin, and paclitaxel) regimen in 2018 as a treatment option for patients with nonsquamous NSCLC in the metastatic setting. 3 In one of the only phase 3 CPI studies to include patients with EGFR mutations (10% of the trial population), an initial subgroup analysis in this group had improved progression-free survival (PFS) with ABCP over BCP (bevacizumab plus carboplatin and paclitaxel) alone, with a hazard ratio (HR) of 0.59 very similar to the overall intention-to-treat (ITT) population (0.61). In a separate analysis in 2019, the authors concluded that overall survival (OS) was also improved in the EGFR mutation-positive (EGFR mutationþ) group with the ABCP regimen. 5 On the basis of these subgroup analyses, some oncologists and centers adopted the ABCP regimen as a preferred option after progression on TKI, 6 and the European Medicines Agency even extended approval of ABCP to EGFR mutationþ patients. 7 Recently, however, the final analysis of the EGFR subgroup was published by Nogami et al. 8 in the Journal of Thoracic Oncology. The disappearance of a statistically significant OS benefit in these updated results should be a warning light for practitioners who have adopted routine use of ABCP in this patient population.CPIs have become a routine part of the treatment of patients with metastatic NSCLC, but the use of CPIs in EGFR mutationþ patients has been much less fruitful.
1069 Background: Cytogenetic data plays an important role in assessing prognosis and determining choice of therapy for AML. Traditionally, patients with AML are treated with infusional cytarabine and an anthracycline. CR rates with this regimen have been reported at 50–60%. Evaluation of novel treatment regimens for AML should include determination of the impact of the regimen on intermediate and unfavorable cytogenetics. We present a retrospective analysis of a 2-day remission induction regimen, based on the concept of timed sequential therapy. The regimen combines high dose cytarabine, which has been shown to improve remission rates when used in induction therapy, and dose intensified anthracycline therapy, which has been shown to improve outcome in younger patients. The cycling cells are eradicated during an initial pulse of therapy, then, previously quiescent cells are targeted during the second pulse of therapy. Here we present the analysis of the study regimen and the response rates of patients with intermediate and unfavorable cytogenetic profiles. Patients and Methods: One hundred fifty five patients categorized as having intermediate or unfavorable cytogenetics were treated with timed sequential chemotherapy from 1998–2009. The treatment regimen consisted of two doses of cytarabine 2 gm/m2 IVPB given over 3 hours, administered 12 hours apart. This was followed by one dose of mitoxantrone 30 mg/m2 IVPB over 1 hour on days 1 and 5. Pre-therapy cytogenetic data was collected for each patient. Responses to therapy were determined based on IWG response criteria for AML. Results: One hundred fifty five patients with intermediate and unfavorable karyotypes received high dose cytarabine and mitoxantrone for remission induction therapy. Median age of patients was 55 years (ranged from 17–85). Sixty patients were 60 years or older. Eighty three patients (53.5%) had intermediate and 72 (46.5%) had unfavorable karyotypes. The younger patients (under 60 years of age) with intermediate cytogenetics achieved the following responses: 34 CR, 6 CRi, and 2 CRp. The overall response rate (ORR) was 80.8% for these younger patients, while the ORR for the older patients (over 60 years of age) with intermediate cytogenetics was 77.4% (15 CR, 4 CRi, 5 CRp). In the unfavorable cytogenetic category, the ORR of the younger patients (under 60 years of age) was 60.5% with 13CR, 8 CRi, and 5 CRp, while an ORR of 44.8% was shown in the older patients (over 60 years of age) with 9 CR, 1 CRi, and 3 CRp. Overall, twenty two out of seventy two (30.5%) had CR in the unfavorable group, 9 (12.5%) had CRi, and 8 (11%) had CRp for an overall response rate of 54%. The 30 day mortality rate was 3.8% (6/155). The 60 day mortality rate was 11.6%. The most common adverse events were Grade 3/4 hematologic toxicities. Conclusion: This convenient, 2-day induction regimen leads to high response rates with low treatment-related mortality in older patients and patients with unfavorable cytogenetic characteristics. Based on the tolerability and effectiveness, this regimen could potentially be useful in high risk transplant-eligible patients for remission induction. It appears that this regimen would also be appropriate for initial cytoreduction in elderly patients with AML prior to introduction of novel therapeutic strategies, such as hypomethylating agents or oral clofarabine for consolidation and maintenance. Disclosures: No relevant conflicts of interest to declare.
e21156 Background: The identification of driver mutations and development of targeted therapies have significantly improved outcomes of patients with advanced non-small cell lung cancer (aNSCLC). It has been shown in clinical trials that immunotherapy (IO) has limited effectiveness in patients with aNSCLC and driver mutations, but as there is a lag in the widespread use of targeted agents for newer driver oncogenes it is important to define the efficacy of non-targeted treatments. We sought to explore the real-world treatment patterns and outcomes of patients with aNSCLC and driver mutations treated with first-line (1L) chemotherapy (chemo) as compared to chemo +/- IO. Methods: This retrospective study utilized the COTA real-world database, a de-identified database derived from the electronic health records of healthcare providers in the United States. Patients included in the study had diagnosed aNSCLC and at least one positive test result for BRAF v600, HER2 mutation, EGFR, MET, RET or ROS1 prior to the initiation of 1L therapy. Additionally, patients must have received frontline chemotherapy, IO monotherapy, or IO+chemo combination in the advanced setting. Outcomes to first-line treatment (real-world progression-free survival (rwPFS) and real-world time to next treatment (rwTTNT)) were calculated using the Kaplan-Meier method. Results: A total of 170 qualified patients were identified as having at least one positive mutation and having received frontline chemotherapy (n=119), IO monotherapy (n=28), or chemo+IO combination (n=23). Mean age was 65 yrs and patients were predominantly white (71.2%), treated in the academic setting (74.1%), and denovo metastatic (67.1%). Outcomes to 1L treatment are reported in Table. Patients treated with 1L chemo+IO combination had longer rwPFS and rwTTNT as compared to patients treated with chemo alone or IO monotherapy, though outcomes did not reach statistical significance. Conclusions: Our study showed that in a real-world population of patients with aNSCLC and driver mutations, patients treated with chemo+IO combination had longer rwPFS and rwTTNT as compared to those treated with chemo alone or IO monotherapy. The overall short duration of benefit supports the model of using targeted treatment as optimal first line therapy, and the overall lack of benefit from IO. [Table: see text]
1068 Background: Patients with AML who are eligible for chemotherapy are traditionally treated with infusional cytarabine and an anthracycline. CR rates with this combination have been approximately 50–60% with an induction mortality of 10–25%. However, this treatment is less effective in older patients in terms of CR attainment, remission duration, and overall survival. We present a retrospective analysis of an induction regimen that was designed based on the concept of timed sequential therapy. An initial pulse of chemotherapy is administered to eradicate cells in S phase. This is followed by a rest period during which previously quiescent cells that enter the cell cycle can be targeted by a second pulse of chemotherapy. The regimen incorporates high dose cytarabine, which has been shown to improve remission duration when used in induction, and dose-intensified anthracycline therapy, which has been shown to improve outcomes in younger patients. This report highlights the responses and tolerability of the study regimen, particularly in elderly patients and patients with prior myelodysplastic syndrome (MDS). Patients and Methods: One hundred sixty six patients were treated with timed sequential chemotherapy from 1998–2009. The treatment consisted of two doses of cytarabine 2 gm/m2 IVPB over 3 hours administered 12 hours apart followed by one dose of mitoxantrone 30 mg/m2 IVPB over 1 hour on days 1 and 5. Data on pre-therapy cytogenetics and MDS was collected for each patient. Remission status was assigned per the IWG response criteria for AML. Results: Median age of the patients was 54.5 years (range 17–85). There were eighty males and eighty-six females. Out of 166 patients, 11 (6.6%) patients had favorable, 83 (50%) had intermediate, and 72 (43.4%) had unfavorable karyotypes. One-third of the patients (57 pts) had AML transformed from MDS. The overall response rate (ORR: CR+CRi+CRp) for all patients was 69.9%. In patients who had de novo AML, the ORR was 79.8%, regardless of age. Patients over age 60 with de novo AML had an ORR of 74%. For those patients under the age of 60, the ORR was 82%. The ORR for patients with transformed AML was 52.6% (53% in pts over age 60, 52% in pts less than 60). The 30 day mortality rate was 3.4% (6/166). Five of the six patients who died had an unfavorable karyotype with 2 patients having therapy-related AML. The 30 day mortality for patients older than 60 was 3.3% (2/61) and for all patients was 3.6% (6/166). The 60 day mortality rate in all patients was 10.8% (18/166). Of the additional 12 patients, seven died from progressive disease and only 3 died of suspected therapy-related complications. Grade 3/4 hematologic toxicities were the most common adverse events seen. Conclusion: This is a convenient, 2-day induction regimen that is well-tolerated with comparatively low 30 and 60 day mortality and high response rates in older patients and those patients with AML transformed from MDS. This would be an excellent initial regimen for remission induction in a select population of patients in whom novel consolidation or maintenance therapies can be incorporated to further improve outcome. Disclosures: No relevant conflicts of interest to declare.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.