Precision medicine was an important theme of ASCO 2018 — the annual meeting of the American Society of Clinical Oncology — with this year’s meeting subtitled as “Delivering Discoveries, Expanding the Reach of Precision Medicine.” This theme was reflected not only in discussions around molecular profiling of patients, but also by the ever-increasing focus on tailoring both new agents and combination therapies to the expression of specific cancer markers and tumor mutations.
We heard a lot of good news from ongoing studies. As we previously highlighted in our ASCO preview, Loxo was one of the winners with their tumor agnostic RET inhibitor, Loxo-292, showing high overall response rates in lung, thyroid and pancreatic cancers, even in heavily pre-treated patients.
Non-Small Cell Lung Cancer
Squamous non-small cell lung cancer (NSCLC) was also a big topic this year. Both Merck and Roche reported good data in first line for their PD-1/PD-L1 inhibitors, with Merck taking the spotlight for Keytruda in combination with chemotherapy. Data from the Keynote-407 study showed that the drug combination could cut the risk of worsening disease by 44% and risk of death by 36% across all patients, regardless of PD-L1 status compared to chemo alone. Roche reported that the combination of Tecentriq and chemotherapy (IMpower131) reduced the risk of worsening disease or death by 29% compared with chemo alone. The two companies’ studies were differently designed and run, making comparisons difficult, and the survival data from Roche’s Tecentriq trial is not yet mature. So ultimately, both drugs should be considered as showing notable successes in this indication.
The continuing success of Keytruda in NSCLC — even in patients with minimal PD-L1 expression — may also herald the end of an era for first-line chemo as a treatment for lung cancer patients. Researchers from the University of Miami Health System reported that in patients with only 1% or greater PD-L1 expression, Keytruda was associated with a 20% increase in survival compared to chemo alone. In patients with higher PD-L1 expression, the benefit was even higher: 23% better overall survival in patients with >20% PD-L1 expression, and 31% better survival in patients with >50% PD-L1 expression.
Unfortunately, the news for Keytruda in EGFR+ NSCLC was somewhat more disappointing. Results from a small open-label Phase 2 study suggest that the use of Keytruda prior to EGFR tyrosine kinase inhibitor (TKI) therapy might be unsafe for TKI-naive patients with EGFR-mutant NSCLC. Not only did the trial produce a 0% objective response rate, but three of the 11 patients treated experienced serious adverse events.
Moreover, data from the closely watched ECHO-301 study of Keytruda plus Incyte’s IDO inhibitor epacadostat was disappointing, as the combination performed no better than Keytruda alone in advanced melanoma patients.
We also heard both promising and disappointing news about T-cell therapeutics. While CAR-Ts (chimeric antigen receptor T cells), which are T cells engineered in the laboratory with specific cancer-recognizing receptors, have shown striking success against blood malignancies, they have been much less successful against solid tumors, possibly because of the immunosuppressive environment of such tumors.
However, a striking case on the use of adoptive tumor infiltrating lymphocytes (TILs) in breast cancer suggests great potential for another T cell approach in solid tumors. A woman with advanced, highly aggressive, metastatic breast cancer who had been told she had only months to live, experienced the disappearance of her cancer after she was treated with TILs harvested from one of her chest tumors. She was treated by Dr. Steven Rosenberg, Chief of the Surgery Branch at the National Cancer Institute’s Center for Cancer Research (who was also at the center of many early CAR-T advances), who used high throughput screening to determine which TILs were able to recognize her tumor cells. Those cells were expanded and reinfused into the patient. Within 12 months, all of her tumors were gone, and she has now been cancer-free for two years. According to Rosenberg, 23% of the harvested TILs proved useful, targeting 4 of 62 mutations found in the patient’s tumors. This adoptive cell therapy method has been used previously with mixed success in bowel, cervical and liver cancers, but this was the first report of its use in breast cancer.
In our next post, we’ll talk more about the use of cancer screening panels and some of the latest advances in liquid biopsy.