As I described in a post describing the general principles of SCLC, it is typically responsive to treatment initially, but upon recurrence it is much less likely to respond. Given that pattern, the value of maintenance therapy has been tested in ED-SCLC, where treatment with initial standard doublet chemo was followed immediately by single-agent “maintenance chemotherapy”, in hopes of delaying progression to a point where a resistant, progressive SCLC emerges.
One of the most instructive trials in this regard is the Eastern Cooperative Oncology Group (ECOG) Trial 7593 (abstract here), in which just over 400 people with ED-SCLC received four cycles of cisplatin and etoposide, a standard approach for this clinical setting, followed by topotecan/hycamtin, a drug that is FDA-approved for recurrent SCLC, or no further therapy until the time of progression (the standard approach):
Of the 402 who entered, only 223 got through those 4 cycles of doublet chemo without progression or some other complication that kept them from moving on to the maintenance phase. What the investigators found was that maintenance topotecan produced a significant delay in progression (3.6 vs. 2.3 months after randomization to maintenance or observation). That’s great, but it unfortunately didn’t translate to any improvement at all in overall survival (9.3 vs. 8.9 months for maintenance vs. observation, respectively). And there was a cost in terms of significant side effects, particularly in terms of low blood counts, from maintenance chemo. There was also an assessment of quality of life for patients on both arms, and there were no clear differences either way. Overall, this trial provided no clear reason to pursue maintanance chemo.
Another trial by Hanna and colleagues (abstract here), done by the Hoosier Oncology Group (known affectionately as the HOG) tested the approach of maintenance chemotherapy with oral etoposide, which is a very convenient alternative active drug in SCLC and sometimes used in the recurrent setting, although not as commonly as topotecan. This trial had a very similar design as the ECOG trial. All of the 233 enrolled patients with ED-SCLC started with four cycles of a slightly different chemo, a triplet combination of cisplatin, etoposide and ifosfamide that is not commonly used except by the HOG, but did suggest a better survival than standard cisplatin/etoposide, but with greater toxicity (abstract here). After those four cycles, 144 patients went on without progression to be randomized to maintenance oral etoposide (a low dose of 50 mg by mouth 21 of 28 days in each cycle) for up to three months:
As in the ECOG trial, there was a significantly longer time until progression in the patients who received maintenance chemo (8.2 vs. 6.5 months from the start of the trial), and the overall survival was not significantly different between the two arms. There was a modest one month difference, 12.2 vs. 11.2, favoring the maintenance chemo recipients, and there was also a somewhat better overall survival for the maintenance chemo arm at one year (51.4% vs. 40.3%) and two years (8.8% vs. 1.8%). These were not significant differences, but this trial was really too small to detect subtle differences.
So at this point, with two negative trials, maintenance chemotherapy for SCLC is not the standard approach. However, both of these trials were fairly small and had more than 1/3 of the patients drop off before getting to the maintenance portion. Overall, there isn’t enough to change our practice, but with some hints of benefit, particularly in the smaller HOG trial, I would say this is still a valid question to pursue further, particularly if we can identify a targeted therapy that may be minimally toxic and effective in SCLC, therefore lending itself to longer-term use. Such a treatment has been quite elusive thus far, though, as we struggle to improve on our old standards for ED-SCLC.