‘How We Treat First Line Patients’ is The Key to Moving Forward in New Lung Cancer Treatments

Different immunotherapy approaches, with or without chemotherapy, and other new therapies were discussed in a virtual COA (Community Oncology Alliance) 2020 Community Oncology Conference session on Friday.

Alexander Spira, MD, PhD, FACP, director of Clinical Research at Virginia Cancer Specialists and co-chair of the Thoracic Oncology Committee at US Oncology Research, discussed how there are many types of malignancies when it comes to lung cancer, and we need to set this paradigm for our patients in the future.

Spira explained an example of an immunotherapy approach, which was the study KEYNOTE-189, analyzing adenocarcinoma, carboplatin, and pemetrexed, and this combination therapy’s effect on patients. The results of the study showed that the combination therapy showed better results in patients, using a PDL to determine who does better with immunotherapy.

“PDL testing is a marker of whether or not cells in tumor specimen express PDL,” Spira explained. “It has huge variability, which makes this not as good as a marker. We still are trying to find another test to represent a better biomarker.”

PDLs are ranked as less than 1%, greater than 1%, or greater than 50%.

In regard to the KEYNOTE-189 study, one of the most shocking things Spira said he saw was that the patients with a lower PDL score had a higher response rate with a chemotherapy combination treatment instead of a lower response rate.

“With this information, we need to learn more about how this occurs and about biomarkers,” Spira said.

On the other hand, if you find a patient who has a high PDL, Spira reminded the audience, toxicity is expected and there is a likelihood of getting to second line RX, at approximately 50-60%.

“Further, PDL testing is very important in this situation,” Spira said. “Especially as a guide in terms of side effects of a patient, the number of the PDL is important.”

For the first time in oncology, Spira said, he feels there may be no need for chemotherapy in the future of first line therapy in patients who use combination immunotherapy. For example, in the CHECKMATE 227 study analyzing nivolumab and ipilimumab combinations, the results showed a 1- or 2-year survival rate, which is major, according to Spira.

“We would expect chemotherapy to work better in patients with low PDL,” Spira said. “but what shocked people was that the PDL was less than 1% and worked better as a treatment.”

In regard to what is new in targeted therapy, RET fusion and C-met exon 14 skipping are 2 examples of what Spira believes is going to make a difference in lung cancer therapy. Both therapies are known for clinical benefits such as tumor shrinkage and causing fewer adverse effects on patients. However, a challenge is waiting for a mutation analysis to come back.

When looking at next generation sequencing, or NGS, Spira recommended taking action, such as working with the pathology lab, considering blood-based assays, and performing a re-biopsy when appropriate.

REFERENCE

Spira, Alexander. Clinical Update- New Lung Cancer Treatments in the Age of Targeted Immunotherapy. Presented at: COA 2020 Community Oncology Conference 2020. April 24, 2020.