Cancer Treatment Today

It used to be taught that cheoptehrpay should be reserved for patients with performance status of 10 or q; however a recent study by Zukin et al,was a trial performed primarily by a Brazilian research consortium randomly assigned 205 advanced NSCLC patients, with PS2 as defined by two investigators per institution, to either pemetrexed (Pem) as a single agent or in combination with Cb as first line therapy.20 The trial demonstrated a statistically and clinically significant improvement with the doublet in terms of response rate (23.8% v 10.3%; P = .032), progression-free survival (median. 5.8 v 2.8 mos; HR = 0.46; 95% CI, 0.35 to 0.63; P < .001), and OS (median, 9.3 v 5.3 mos; HR = 0.62; 95% CI, 0.46 to 0.83; P = .001). Though four patients on the combination chemotherapy arm (3.9%) experienced treatment-related mortality and there was more toxicity with the combination chemotherapy arm, as expected, the difference in adverse events was modest overall, primarily limited to relatively infrequent grade 3/4 cytopenias.

Before the publication of the Zukin et al study, the subset analysis of PS2 patients from the Cancer and Leukemia Group B 9730 trial of Cb/Pac versus Pac alone in a broader population of patients with PS 0 to 2 revealed a significantly superior survival in with combination chemotherapy (median OS, 4.7 v 2.4 mos; HR = 0.60; 95% CI, 0.40 to 0.91, P = .016). Similarly, though the Intergroupe Francophone de Cancrologie Thoracique (IFCT) 0501 diacritic trial of Cb with weekly Pac versus Vin or Gem monotherapy in the elderly enrolled patients with PS from 0 to 2, the same magnitude of benefit was seen in patients with PS2 compared with those with PS 0 to 1 (HR = 0.63 in both groups). Finally, a trial of US Oncology PS2 patients with advanced NSCLC by Reynolds et al also revealed a strong trend toward superior efficacy with Cb/Gem versus Gem alone (median OS, 7.0 v 5.2 mos; P = NS). These studies support benefit of chemotherapy, even aggressive chemotherapy for patients with PS 2.

NCCN, NSC Luung Cancer 2017

M Zukin, CH Barrios, JR Pereira, etal: Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2 J Clin Oncol 31: 2849 2853,2013

BH Grønberg, RM Bremnes, O Fløtten, etal: Phase III study by the Norwegian Lung cancer study group: Pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer J Clin Oncol 27: 3217 3224,2009

C Reynolds, P Conkling, DA Richards, etal: A randomized phase 3 trial of gemcitabine with or without carboplatin in performance status 2 (PS2) patients with advanced (stage IIIB with pleural effusion or IV) non-small-cell lung cancer (NSCLC): P2-292 J Thorac Oncol 2: S688,2007

CG Azzoli, S Baker Jr, S Temin, etal: American Society of Clinical Oncology clinical practice guideline update on chemotherapy for stage IV non-small-cell lung cancer J Clin Oncol 27: 6251 6266,2009