DR BLUMENSCHEIN: This was originally designed as a trial — it’s a 1,500-patient study for patients who had resectable disease. And for this particular study, it was patients who had at least a 4-cm tumor, up to Stage III patients. If they were resected, they would be able to go on study and they’d received adjuvant chemotherapy, a cisplatin-based doublet, with or without the addition of bevacizumab. The bevacizumab, which was the primary endpoint, the addition to that to the standard combinations was not a positive trial. It was a negative. It was a wash.

So they went back and did a subset analysis on the various chemotherapies. And then they subsetted that by histology. So there was a squamous group, which got docetaxel, gemcitabine, vinorelbine with cisplatin. And then there was a nonsquamous group, which got the aforementioned drugs plus pemetrexed. And the take-home message again was, cisplatin-based doublet — it doesn’t matter what it is — it works equally well.

She went through the various toxicities. And some of the drugs had different toxicities in terms of rates of neuropathy or rates of thrombocytopenia, for example, with gemcitabine. But overall, there was no difference in overall survival or progression-free survival. And I think what this ultimately means for physicians practicing right now is, when you have a patient who’s had resected disease and is a candidate for adjuvant treatment, you take into account their comorbidities and what you think they’re able to tolerate. For example, someone who has underlying peripheral neuropathy, you probably don’t want to give a taxane or vinorelbine. You can give them gemcitabine if they have squamous cell with cisplatin, if you can give cisplatin. Or you can give pemetrexed if they have a nonsquamous tumor.

So I think those are the take-home messages from that. And what they also did to kind of minimize confounding issues with this was they centralized the dose of cisplatin at 75 mg/m² once every 3 weeks, so there weren’t various doses of drugs being given.

I think the take-home is cisplatin is still required to get that survival benefit. And you can add the appropriate drug as part of the combination, based on your practice experience and what the patient’s comorbidities are.

DR LOVE: So in your own practice, how do you approach selecting the partner for cisplatin for squamous and nonsquamous in the adjuvant setting outside a trial setting?

DR BLUMENSCHEIN: So if I have patient who meets the criteria that I just outlined, has the appropriately sized primary tumor or stage of disease, we’ll discuss adjuvant chemotherapy and discuss it has about a 5% overall survival benefit. And then if they don’t have any underlying comorbidities, it’s cisplatin 75 mg/m², either with a taxane or with pemetrexed, depending on the histology. And I do this relatively routinely in my practice unless someone has some underlying issues, or, after we discuss the results, decides they just don’t want chemotherapy, which sometimes happens.

DR LOVE: I guess the one thing about that data set that she presented that was interesting was that we’ve seen, just by surveying both investigators and general oncologists in practice, extensive swift movement toward the use of pemetrexed in nonsquamous in the adjuvant setting. And there’s always been the question of, is there enough solid data behind pem compared to, for example, vinorelbine? And some people felt that these data that she presented sort of was more support for that.

DR BLUMENSCHEIN: And she brought that point up. And they did amend the trial, I think in 2009, to add pemetrexed and cisplatin as an arm for the nonsquamous group because of the data that came out with pemetrexed and cisplatin. And I think there’s an ongoing study evaluating this in a prospective fashion to ascertain if there’s a difference between that.

But when you look back at the older studies from the early 2000s, late ‘90s, the one thing that stands out is, the patients that benefitted all got cisplatin. And, in fact, vinorelbine/cisplatin did the best in those meta-analyses, and they also got the highest dose of cisplatin. So I think cisplatin is a key player in this particular space and then less so the chemotherapy you add on to it. Now, these other chemotherapies have less toxicity and might be a good pairing, such as pemetrexed.

DR LOVE: The other thing that we’ve heard discussed, and there was this so-called TREAT trial that looked at to what extent people actually received adjuvant therapy, in this case I think it was cis/pem and cis/vinorelbine. And I don’t know that she presented the data on percent of dose that was received at the various regimens.

DR BLUMENSCHEIN: I don’t recall her putting on the specifics of it. But I think she did summarize that it was equivalent across all the different arms. It wasn’t one arm that got more than the other in terms of number of cycles or median number of cycles.

DR LOVE: Oh, I see. Oh, that’s interesting. Yes.

DR BLUMENSCHEIN: And for that reason, the data supports that this is kind of a wash, in the sense that the partner with cisplatin doesn’t seem to matter. There wasn’t any confounding variable. And I believe all the different arms had a similar median number of cycles or dose intensity.

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