Alexander Spira, MD, PhD

Alexander Spira, MD, PhD, a medical oncologist and director of the Virginia Cancer Specialists Research Institute and the Phase 1 Trial Program, discusses how he chooses treatment for patients with lung cancer.

Spira says the treatment decisions for patients with lung cancer have become more complicated for the non-biomarker-driven patient population, or patients without an actionable mutation. For this population, physicians have to decide on whether or not to use chemotherapy or chemoimmunotherapy first. Most look at the patient’s PD-L1 expression since higher PD-L1 scores are likely to benefit from checkpoint inhibitors alone, possibly with ipilimumab (Yervoy). Mainly this is dependent upon the individual patient, their risk, how quickly the tumor is growing, and their level of interest in doing chemotherapy. That topic is hotly debated amongst oncologists in the targeted therapy space, he explains.

Targeted therapy is the best option for patients in all those situations, according to Spira. The physician can identify which biomarkers the patient has, either by tissue-based or by blood-based assays. It has been a struggle to get patient’s testing for all the biomarkers, and that's where he thinks liquid biopsies are coming to the forefront. However, most of the targeted options are the best. Spira says the 

 G12C drugs are likely be approved because the studies have been in second line, and once they are approved, there's going to be many studies looking at them in the first-line setting. This may be a non-chemotherapy option that directly targets the patient’s tumor type.

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Alexander Spira, MD, PhD, discusses how he chooses treatment for patients with lung cancer.

Exploring Why Testing in Lung Cancer is Important to Treatment Decisions

Alexander Spira, MD, PhD, a medical oncologist and director of the Virginia Cancer Specialists Research Institute and the Phase 1 Trial Program, shares an important message with community oncologists regarding the treatment of patients with lung cancer.

Test, test, test, says Spira. In order to better treat these patients, physicians need to test advanced patients more appropriately. It’s very challenging to do, Spira admits, but if tests aren’t completed, physicians won’t detect mutations that might alter their treatment plan.

Spira says he can’t speak to how many patients have had a mutation that nobody picked up on, which is why it is so important to test. There are so many new treatments coming down the pike, with new opportunities for these patients with advanced lung cancer. Patients should be enrolling to clinical trials, which is another important thing to do for this patient population, Spira says.

Alexander Spira, MD, PhD, shares an important message with community oncologists regarding the treatment of patients with lung cancer.

Testing Early & Often Recommended for Patients With Lung Cancer

Alexander Spira, MD, PhD, a medical oncologist and director of the Virginia Cancer Specialists Research Institute and the Phase 1 Trial Program, discusses the phase 1 CHRYSALIS trial of amivantamab (JNJ-61186372) plus lazertinib (YH25448) in 2 

-mutant non–small cell lung cancer patient populations, which include patients with relapsed/refractory and those who are treatment-naive.

In the relapsed/refractory population, there was about a 36% or 37% response rate, with significantly more patients benefiting. This is good because it's designed as a non-chemotherapy option since chemotherapy would be the normal approach for these patients, according to Spira. Since the proof of concept worked, there is potential for a non-chemotherapy option in this setting.

Spira explains the investigators combined these drugs because amivantamab is a monoclonal antibody, which do not tend to penetrate the brain, and by continuing to administer with the small molecule lazertinib, the idea is that you could both overcome resistance, as well as prevent brain recurrence, in addition to having a 2-fold attack on tyrosine kinase inhibitor therapy.

The second patient population of those who were treatment naïve had a 100% response rate. Spira says this is almost unheard of. With this combination, standard EGFR toxicities were increased more than we would typically see. Most commonly, these included nail changes or a rash. Because of amivantamab is a fusional drug and a monoclonal antibody, there were some infusion-related reactions. With good monitoring, most patients were able to get the first dose split over 2 days.

Alexander Spira, MD, PhD, discusses the phase 1 CHRYSALIS trial of amivantamab plus lazertinib in 2 EGFR-mutant non–small cell lung cancer patient populations, which include patients with relapsed/refractory and those who are treatment-naive. 

Alexander Spira, MD, PhD | Authors

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