Roughly two-thirds of people with non–small cell lung cancer (NSCLC) are diagnosed at stage IIIB or IV and can benefit only from palliative chemotherapy. This prospective randomized trial found that switch maintenance therapy outperformed best supportive care (BSC) alone when following platinum doublet chemotherapy in these patients [Jakhar SL et al. Ann Oncol. 2015]. Christian Manegold, MD, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany, discussed the results of a study based on a poster by Shankar Lal Jakhar, MD, Acharya Tulsi Regional Cancer Treatment & Research Institute, Bikaner, Rajasthan, India, and colleagues.

For switch maintenance after platinum-paclitaxel chemotherapy, gemcitabine (G) was chosen as a different active agent aimed at preventing replication of clonal variants that slipped through first-line palliative treatment. Overall survival (OS) was the primary end point of this open-label study. The secondary end point was progression-free survival (PFS).

Patients with stage IIIB and IV NSCLC (N = 134; median age, 50 years) were enrolled in the trial between July 2011 and January 2012. None had received chemotherapy. Roughly half (50.7%) had stage IV disease, and 76.8% were men. Two-thirds (67.9%) were ECOG performance status 0/1, and the remainder were status 2.

Participants underwent 6 three-week cycles of cisplatin (40 mg/m², cycle days 1 and 2) and paclitaxel (175 mg/m², cycle day 1). Following this, the 99 nonprogressing patients were randomly assigned 1:1 to maintenance gemcitabine (1000 mg/m², cycle days 1 and 8) every 3 weeks or BSC until their disease progressed.

Gemcitabine significantly lengthened OS and PFS compared with BSC alone (Table 1). Prof Manegold mentioned other trials of gemcitabine as maintenance and not switch therapy; the findings of this trial support results from a larger trial of gemcitabine maintenance therapy [Brodowicz T et al. Lung Cancer. 2006] yet stand in contrast to a trial [Belani CP et al. J Clin Oncol. 2010] that found no advantage for gemcitabine maintenance plus BSC vs BSC alone.

Patients in the gemcitabine group experienced a higher incidence of grade 3 and 4 adverse events: anemia (12% G; 8.1% BSC), neutropenia (18% G; 4.1% BSC), thrombocytopenia (14% G; 2% BSC), and fatigue (8% G; 2% BSC). Otherwise, the researchers reported that maintenance therapy was well tolerated.

This study has a number of limitations that affect its interpretation. These include the open-label design, which could have influenced the results because the patients and the investigators knew who was receiving active treatment. The histologic subgroups (ie, squamous, nonsquamous) were not reported. Importantly, there is no information about the frequency of follow-up visits or restaging of cancer by imaging for each group and the percentage of patients who eventually had second-line therapy, particularly in the BSC group. The results of this small study may provide a signal that switch maintenance therapy with gemcitabine may extend OS and PFS for patients with advanced NSCLC, a finding that must be interpreted carefully and balanced against the increase in high-grade toxicity.