Dr Gadgeel Discusses Pembrolizumab, Platinum-Based Chemo in EGFR/ALK-Positive NSCLC

Shirish Gadgeel, MD, Henry Ford Health System, Detriot, MI, shares insight on pembrolizumab in combination with platinum-based chemotherapy in recurrent EGFR/ALK-Positive non-small cell lung cancer (NSCLC).

Transcript:

Dr. Shirish Gadgeel: My name is Dr. Shirish Gadgeel. I'm Chief of the Division of Hematology/Oncology at Henry Ford Cancer Institute, Henry Ford Health System in Detroit, Michigan. Today, I'm going to be discussing the results of the study that I presented at World Conference of Lung Cancer 2021 that was held from September 8th to September 14th.

A brief background to the clinical trial that I presented. Though many patients derive significant benefit from tyrosine kinase inhibitors in patients with EGFR and ALK-positive non-small cell lung cancer, eventually, almost all patients develop disease progression. At the present time, at least, there are very limited targeted therapy options for patients who progress on frontline TKI therapy.

In many of these patients, combination platinum-based chemotherapy is utilized. However, the clinical benefits of such therapy are fairly modest, with a median progression-free survival of approximately five months and a response rate of 30 percent.

There is a need to develop novel therapies for patients who have TKI-refractory EGFR and ALK-positive non-small-cell lung cancer. Immune checkpoint inhibitors have been evaluated in these patients, but the activity of these agents as single agents has been extremely limited, with response rates of only about three to four percent.

In KEYNOTE-189, chemotherapy plus pembrolizumab improved response rate progression-free survival and overall survival in advanced non-small-cell lung cancer patients whose tumors did not have EGFR or ALK alterations. Therefore, we conducted this clinical trial to evaluate the efficacy of chemotherapy plus pembrolizumab in TKI-refractory EGFR and ALK-positive non-small-cell lung cancer.

Briefly, the eligibility was that patients with EGFR-positive or ALK-positive non-small-cell lung cancer that were previously treated with appropriate tyrosine kinase inhibitor therapy were eligible for the trial.

As far as EGFR mutations are concerned, not only the classical mutations, exon 19 deletion and exon 21 L858R mutation, patients were eligible, but also other uncommon mutations but known to be sensitive to EGFR TKI, such as exon 21 L861Q mutation-positive patients were also eligible. Patients with asymptomatic brain metastases were eligible.

So were patients who have received one cycle of platinum-based chemotherapy, as long as that cycle was administered while awaiting molecular results before initiating targeted therapy. We conducted a few correlative studies, which included tumor PD-L1 assessment as well as a collection of blood for circulating tumor cells.

All eligible patients were treated with carboplatin, pemetrexed, and pembrolizumab at their standard doses, administered every three weeks. For the first six cycles, scans were conducted after every two cycles for assessment of disease status. Then, after six cycles, the frequency of scans was determined by the treating physician.

This was a single-arm multicenter two-cohort study that enrolled both EGFR and ALK patients. The statistical design required enrollment of a total of 28 patients in each cohort.

It was a two-stage design. In the first stage, in each cohort, we had to enroll 14 patients. If efficacy parameters were met, then further patients were enrolled to a total of 28 patients.

The study was closed early because of slow enrollment. This was attributed to both the availability of this regimen in the community as well as because of the COVID-19 pandemic.

We enrolled 33 patients, of which 26 patients had EGFR mutation-positive lung cancer and seven patients had ALK-positive non-small-cell lung cancer. About 90 percent among EGFR patients had either exon 19 deletion or L858R mutation, and approximately, 30 percent of the patients had baseline brain metastases. The median number of prior treatments was one.

The response rate was 48.3 percent among patients with EGFR mutation-positive non-small-cell lung cancer. It was 28.6 among ALK patients.

The progression-free survival among EGFR patients was 8.2 percent, and 12-month progression-free survival was 29 percent. Among ALK patients, those numbers were 2.8 months and 14 percent.

The overall survival among EGFR mutation-positive patients was approximately 22 months, with one-year overall survival of 76 percent. In ALK patients, the one-year survival was 14 percent, and the median overall survival was 2.8 percent.

We did not find a difference in efficacy based on tumor PD-L1 expression in that patients with PD-L1-positive tumors had a similar outcome as patients with tumor PD-L1 that was negative.

We did assess circulating tumor cells. We were able to do so in about 15 patients. The data was intriguing, but no conclusions could be drawn because of a very limited number of patients. Toxicity was, as one would expect with this regimen, there were no unexpected toxicities.

Our conclusion from this trial was that this regimen did demonstrate promising results in TKI-refractory EGFR mutation-positive non-small-cell lung cancer, with response rates of about 42.3 percent and a median progression-free survival of 8.2 months.

Among ALK patients, very difficult to draw any conclusions because only seven patients were enrolled. At least, based on the data among these seven patients, the activity of this regimen appears extremely limited in ALK-positive patients.

Our conclusion was that, based on these results, this regimen should be further evaluated in TKI-refractory EGFR mutation-positive non-small-cell lung cancer.