KEYNOTE-028 and KEYNOTE-158: Pembrolizumab as treatment for advanced SCLC after two or more lines of prior therapy

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Published: 15 Apr 2019
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Prof Hyun Cheol Chung - Yonsei University, Seoul, South Korea

Prof Hyun Cheol Chung speaks to ecancer at the 2019 American Association for Cancer Research (AACR) meeting about results from the KEYNOTE-028 and KEYNOTE-158 studies looking at Pembrolizumab as treatment for advanced small-cell lung cancer (SCLC) after two or more lines of prior therapy.

Prof Chung reports that in KEYNOTE-028 patients were PD-L1 positive and the response rate seen was around 30%.

He also reports that a response rate of 19% was seen in KEYNOTE-158 (patients who did not express PD-L1) but promisingly the survival rate was 19 months.

Read more about this research here.

Small cell lung cancer is a very poor disease and is only 15% of lung cancer but only 20% of cancer patients get to third line treatment. Even in the third line treatment only 10% of patients survive after one year and only 5% survive after two years. So we need more treatments for these poor patients. For these patients immune oncologic agents were developed about 4-5 years ago for small cell lung cancer patients. The first one is KEYNOTE-028: they enrolled patients with PD-L1 positive patients and the response rate was around 30%, that was good. After that if there is some signal, we found some signature, we did KEYNOTE-158 that is a multi-cohort trial in those patients regardless of PD-L1 expression to see the efficacy in PD-L1 positive patients or negative patients. There we see the 19% response rate, that is not bad. So here we want to compare the KEYNOTE-028 and KEYNOTE-158 patients to see whether there is any survival benefit if treated with more than two lines of chemotherapy. The patients were around 83% of patients and we see the response rate around 19%. That was very nice because in chemotherapy the response is around 20% but the survival is only four months but here we found a median duration of response of more than 19 months. So that is a very deep response for those patients. So even if the patient number is not that high, if there is a response that patient survives long so that is a signature for these poor patients.

How did the toxicity profile look?

Thinking about the toxicity profile, initially we worried about the toxicity but even if the patients did not get a long treatment the toxicity was not that bad. Over 60% suffered from toxicity that was only grade 1 or 2, the grade 3 toxicity was around less than 10%. But with chemotherapy the severe toxicity comes from 40-60% so it’s really tolerable and this good tolerability is good for the treatment effect, also the maintenance of good performance status, moving the patient to the next treatment cycle, the fourth line of treatment. That is very important.

What will we see over the next year of this study?

It’s very hard to get the patients with third line treatment so as we saw a strong signature in third line patients the drug will be moved on to the early phase, to the second line or third line. The other drug did a head-to-head comparison in second line and the treatment was a failure so pembrolizumab will go to the second line to compare the trial, the phase III trial. For the phase I trial, the other drug relays success in the phase I trial of chemotherapy plus an immune oncologic agent. Also pembrolizumab is ongoing right now so probably I hope at the end of this year if they come out we can have some more arms for the cancer patient from the first line to third line.