Clinical Approach for Unresectable Locally Advanced NSCLC - Episode 3
Jyoti Patel, MD:Our patient who had borderline pulmonary function and multistationed stage 3A disease has a couple of options for therapy. Because he’s not a candidate for resection, he’d be treated with concurrent chemoradiation, which is feasible. Certainly, we have data over decades that show that concurrent therapy is better than sequential therapy, and sequential therapy, by and large, we save for patients in whom toxicity would be a significant issue.
So, for this gentleman, there are multiple regimens in which we could treat him. Because he has adenocarcinoma histology, reasonable regimens would include everything from weekly carboplatin/paclitaxel to cisplatin/etoposide or just cisplatin/pemetrexed. There’s no 1 clear winner. These regimens are often defined by what expected toxicities we would imagine. So, in a patient with preexisting neuropathy or renal dysfunction, likely we would do weekly carboplatin/paclitaxel. For a patient who had good renal function, likely we would do cisplatin/etoposide or cisplatin/pemetrexed.
For this gentleman, I chose cisplatin/etoposide primarily because that is a regimen with which I have significant comfort. The chemotherapy fits completely during the duration of radiation, and so it’s discrete over those 6 weeks. And because the toxicity tends to be minimalmaybe some alopecia and some myelosuppression—generally, it’s quite well tolerated.
So, certainly our treatment of stage 3 disease has evolved over time, as now we’ve gotten closer to an appropriate radiation dose where, normally, patients in the United States are treated between 60 and 66 gray. What has not been as clear in recent years is what the appropriate chemotherapy backbone is for these patients. A widely adopted standard based on phase II data and then replicated in the RTOG trial demonstrated that you could give concurrent carboplatin/paclitaxel with radiation followed by consolidation carboplatin and paclitaxel. And that led to a very favorable outcome in the RTOG study.
However, it’s not clear how much that consolidation does, although that has been widely adopted in the United States. Many people though, because of the difficulty of getting consolidation in after chemoradiation, choose to give cisplatin/etoposide. And during that, patients are getting a substantive dose of cisplatinday 1 and day 8 and then again for the second part of the radiation. And so, generally, my feeling is that patients who have that initial chemotherapy regimen with cisplatin/etoposide can or have completed therapy. We know that consolidation docetaxel leads to inferior outcomes, as demonstrated by the Hoosier Oncology Network.
Cisplatin/pemetrexed has been tested in the PROCLAIM trial, and patients got consolidation pemetrexed. Again, we don’t have a comparator without pemetrexed, so, often, we just give the 3 cycles of cisplatin and pemetrexed and call it a day.
Transcript edited for clarity.