Longer-term survival with immunotherapy for patients with non–small cell lung cancer (NSCLC) is once again being applauded by experts in the field.
This time, the data come from trials that tested immunotherapy in the second-line setting for patients who had experienced disease progression with platinum-based chemotherapy. The latest 5-year follow-up from two landmark trials, one with pembrolizumab (Keytruda), the other with nivolumab (Opdivo), show that the survival benefit can persist for years after treatment is stopped.
"These are unprecedented data," Fred R. Hirsch, MD, PhD, executive director of the Center for Thoracic Oncology at the Tisch Cancer Institute, New York City, told Medscape Medical News. He was not involved in either trial and was approached for comment.
Pembrolizumab Survival Data
The new longer-term data on pembrolizumab come from the KEYNOTE-010 trial, which included more than 1000 patients with advanced NSCLC who had previously undergone treatment with platinum-based chemotherapy. The patients were randomly assigned to receive either pembrolizumab or docetaxel for 2 years.
This is the latest update on data from this trial, which has been described as "really extraordinary."
The 5-year overall survival rates were more than doubled in the pembrolizumab groups compared to the docetaxel group, reported Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut. He was presenting the new data at the recent World Conference on Lung Cancer (WCLC) 2020.
Overall results for patients with PD-LI Tumor Proportion Score (TPS) expression >1% show that 15.6% of the pembrolizumab group were still alive at 5 years, vs 6.5% of the docetaxel group.
The results were even better among patients who had high PD-L1 TPS expression (>50%): in this subgroup, 25% of the patients who received pembrolizumab were still alive, vs 8.2% of those who received docetaxel.
In addition, at 5 years, 9.4% of patients who received pembrolizumab were disease free, vs 0.7% of the patients who received docetaxel, Herbst reported.
Hirsch commented that the 5-year survival rate of 25% among patients with high PD-L1 expression who underwent treatment with pembrolizumab is "great progress in lung cancer treatment, there is no doubt about it."
He noted that the results also show that "numerically," it matters whether patients have low PD-L1 expression. "We know from first-line studies that pembrolizumab monotherapy is effective in high PD-L1-expressing tumors, so these data fit very well," he said.
At the meeting, Herbst summarized his presentation on pembrolizumab for patients with NSCLC who had previously undergone treatment, saying that "with 5 years of follow-up, we continue to see a clinically meaningful improvement in overall survival and PFS [progression-free survival].
"Pembrolizumab monotherapy is a standard of care in patients with immunotherapy-naive or previously treated PD-L1-positive advanced non–small cell lung cancer," Herbst stated.
Hirsch was largely in agreement. He believes that for patients with a PD-L1 TPS ≥50%, the standard of care "is practically pembrolizumab monotherapy, unless there are certain circumstances where you would add chemotherapy," such as for patients with a high tumor volume, "where you want to see a very quick response."
Hirsch pointed out, however, that currently, most patients with high PD-L1-expressing tumors are given pembrolizumab in the first line, which begs the question as to what to give those who experience disease progression after immunotherapy.
"That is an open space," he said. "There is a lot of studies going on in what we call the immunotherapy-refractory patients.
"We don't have clear guidance for clinical practice yet," he commented. He noted that there are several options: "Do you continue with chemotherapy? Do you continue with chemotherapy plus another immunotherapy? Do you switch to another immunotherapy?"
Commenting on Twitter, Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, DC, said the results were "very exciting."
However, he wondered whether the results suggest that patients with high PD-L1 expression "may be able to stop" receiving pembrolizumab, whereas those with disease of lower expression "may need longer therapy."
H. Jack West, MD, medical director of the Thoracic Oncology Program, Swedish Cancer Institute, Seattle, Washington, said on Twitter that to him, the "most impressive" aspect was the "new insight about patients stopping pembro after two years but still having two-thirds with sustained response".
He added that he would "love to learn which patients can stop therapy and when, or whether we can do infrequent maintenance IO [immonotherapy]."
Nivolumab Survival Data
Both of these trials compared nivolumab with docetaxel for patients with NSCLC who had experienced disease progression with platinum-based chemotherapy
The pooled analysis showed that the 5-year overall survival rate was more than fivefold greater with nivolumab than with docetaxel, at 13.4% vs 2.6%.
Moreover, more than 80% patients who had not experienced progression with the immunotherapy at 2 years were still alive at 5 years. The percentage rose to more than 90% among those who had not experienced progression at 3 years.
Lead author Julie R. Brahmer, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, and colleagues say the results "demonstrate that nivolumab can provide long-term survival benefit with durable responses and a tolerable safety profile in patients with previously treated, advanced NSCLC.
"Furthermore, some patients appear to maintain prolonged disease control even after stopping systemic therapy," they note.
Hirsch commented that although the survival rates with nivolumab were slightly lower than reported with pembrolizumab in KEYNOTE-010, they could still be "within the range." He said, "I wouldn't conclude that pembrolizumab is better than nivolumab."
Many factors may account for these differences, he suggested, including differences in the patient populations or simply differences in the numbers of patients included.
For him, the "main point" of the new data from both trials is that immunotherapy has shown "tremendous progress compared to chemotherapy."
KEYNOTE-010 was sponsored by Merck Sharp & Dohme Corp. CheckMate 017 and CheckMate057 were sponsored by Bristol-Myers Squibb. Herbst has relationships with Jun Shi Pharmaceuticals, AstraZeneca, Genentech, Merck, Pfizer, AbbVie, Biodesix, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Heat Biologics, Loxo, Nektar, NextCure, Novartis, Sanofi, Seattle Genetics, Shire, Spectrum Pharmaceuticals, Symphogen, Tesaro, Neon Therapeutics, Infinity Pharmaceuticals, Armo Biosciences, Genmab, Halozyme, and Tocagen. Brahmer has relationships with Roche/Genentech, Bristol-Myers Squibb, Lilly, Celgene, Syndax, Janssen Oncology, Merck, Amgen, Genentech, AstraZeneca, Incyte, Spectrum Pharmaceuticals, Revolution, and Roche/Genentech. Hirsch has relationships with Merck, Bristol-Myers Squibb, AstraZeneca, Genentech/Roche, Regeneron/Sanofi, Novartis, and Daiichi.
World Conference on Lung Cancer (WCLC) 2020: Abstract FP13.01. Presented January 28, 2021.
J Clin Oncol. Published online January 15, 2021. Full text
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