Vivek Subbiah, MD: Turning to Dr Ganti, can you comment on the recent progress in treatment of extensive-stage small-cell lung cancer with the availability of immunotherapy-chemotherapy combinations?
Apar Ganti, MD: Sure. Small-cell lung cancer, especially extensive stage, was in need of some advances in the treatment paradigm. For the last 25 years, we’ve been using platinum and etoposide as our backbone regimen. Until recently, there was no other treatment that was shown to be superior to this combination, and it was not for lack of trying. The first study that showed a benefit over standard platinum/etoposide was the IMpower133 study, which showed that adding atezolizumab, a checkpoint inhibitor, to platinum/etoposide increases overall survival. Since then, there have been at least 2 other trials. The CASPIAN study that showed that adding durvalumab to platinum/etoposide was better than platinum-etoposide alone. More recently as the ASCO (American Society of Clinical Oncology) annual meeting a couple of months ago, the addition of pembrolizumab to the same platinum/etoposide backbone regimen was associated with an improved progression-free survival (PFS) compared with platinum/etoposide alone. A smaller randomized phase 2 study looked at nivolumab/platinum/etoposide and showed an improvement in progression-free survival and improvement in overall survival with the addition of nivolumab. We have 4 trials with different checkpoint inhibitors that suggest that adding a checkpoint inhibitor to platinum/etoposide is better than chemotherapy alone. Of these 2 drugs, durvalumab and atezolizumab have FDA approval in this indication.
Vivek Subbiah, MD: Thank you so much. Do you have any comments, Dr Chiang?
Anne Chiang, MD, PhD: Sure. I think this is a very exciting time, as Dr. Ganti said, for small-cell. We’ve had several approvals in the past year and that, compared to 30 years of no approvals, so we’re very excited. The IMpower133 trial and CASPIAN trial have really defined the frontline standard of care. The IMpower133 trial showing OS (overall survival) of about 12.3 months versus 10.3 months and a hazard ratio of 0.76. The updated CASPIAN data just presented at ASCO showing 13 months versus 10.3 months overall survival with a hazard ratio of 0.73. It’s interesting. The point made on the CASPIAN trial is that the separation of curves at 2 years, that survival improved from 14% to 20% on the experimental arm versus control arm. That is that tail of the curve. It’s something we’re really excited about and looking for in this population, which clearly doesn’t have the median overall survival; it’s about a little over a year. We definitely need more research and ongoing investigation into to new therapeutic agents and options, but the addition of immunotherapy does help us have hope that there are some patients who can have really long-term survival.
For the CASPIAN trial, the combination of tremelimumab and durvalumab did not help, so adding that anti—CTLA4 antibody did not help. Just a word on KEYNOTE-604, which was the pembrolizumab trial: This was not statistically significant but certainly did have the overall survival and progression-free survival trends in the right direction. It looks very promising, but because of the way the study was conducted, it did not have statistical significance. The nivolumab/platinum/etoposide trial, ECOG-5161, was phase 2 but looked promising. The primary end point was PFS. The last thing I would add is that we have a couple of options upfront. How do you decide? It’s not absolutely clear that 1 is much better than the other, which is great. We have options for our patients. I think 1 of the differences in the CASPIAN trial was that it did allow asymptomatic brain metastases. If I have a patient who does have asymptomatic brain metastases, I might be more inclined to use that durvalumab regimen in combination with chemotherapy.
Transcript Edited for Clarity