Chad V. Pecot, MD, associate professor of oncology, Department of Medicine, University of North Carolina Lineberger Comprehensive Cancer Center, discusses selecting between available targeted therapies in 

ex14) skipping–mutant non–small cell lung cancer (NSCLC).

Selpercatinib (Retevmo) and pralsetinib (Gavreto) are FDA-approved options to treat patients with 

-mutant NSCLC. Capmatinib (Tabrecta) and tepotinib (Tepmetko) are available for use in patients with NSCLC who harbor 

ex14 skipping mutations. Although sotorasib (Lumakras) is the only FDA-approved targeted option for patients with 

 G12C mutations, adagrasib (MRTX849) has received a breakthrough therapy designation from the FDA and could be approved soon. 

These options are highly potent and effective for their respective subgroup of NSCLC, Pecot says. Additionally, the agents are more selective against 

ex14 skipping mutations, respectively, compared with earlier generation inhibitors.

As such, physician comfort tends to drive treatment selection between the available agents, Pecot explains. In the academic setting, many clinicians had the opportunity to utilize specific agents in clinical trials, so their comfort level with that agent vs the other may be greater, Pecot concludes.

Videos

Chad V. Pecot, MD, discusses selecting between available targeted therapies in RET-, KRAS-, and MET exon 14 skipping–mutant non–small cell lung cancer.


Dr. Pecot on Selecting Between Available Targeted Therapies in NSCLC 

Chad V. Pecot, MD, associate professor of oncology, Department of Medicine, University of North Carolina Lineberger Comprehensive Cancer Center, discusses addressing mechanisms of resistance with new targeted therapies in non–small cell lung cancer.

Repotrectinib is an agent that is under development that may represent a more potent inhibitor of 

 mutations compared with other available agents in the paradigm, according to Pecot. 

are fusion events. When a patient has a lung cancer that is driven by these mutations, the translocation creates a chimeric protein based on their fusion partner, Pecot explains. 

Tumors that harbor these mutations can create mechanisms of resistance, sometimes referred to as “gatekeeper” or “hot spot” mutations, that can reject potent drugs like alectinib (Alecensa), erlotinib (Tarceva), and brigatinib (Alunbrig) rendering them inactive, Pecot adds. As such, newer agents such as repotrectinib and cabozantinib (Cabometyx) are being evaluated to address these mutations and overcome these mechanisms of resistance, Pecot concludes. 

Chad V. Pecot, MD, discusses addressing mechanisms of resistance with new targeted therapies in non–small cell lung cancer.

Dr. Pecot on Addressing Mechanisms of Resistance With New Targeted Therapies in NSCLC

Chad V. Pecot, MD, associate professor of oncology, Department of Medicine, University of North Carolina (UNC) Lineberger Comprehensive Cancer Center, discusses the growth of actionable targets in lung cancer.

The integration and expansion of targeted therapy has revolutionized the treatment of patients with lung cancers that harbor actionable alterations, Pecot says.

 mutations, next-generation targeted therapies offer more potent and specific options that elicit less off-target adverse effects compared with first-generation agents, Pecot explains. 

 G12C mutations, were identified decades ago but were unable to be targeted effectively, says Pecot. Now, sotorasib (Lumakras), which was FDA approved on May 28, 2021, for patients with 

 G12C–mutated lung cancer who have received at least 1 prior systemic therapy, offers a reasonable option for this patient population, concludes Pecot. 

Chad V. Pecot, MD, discusses the growth of actionable targets in lung cancer.  



Dr. Pecot on the Growth of Actionable Targets in Lung Cancer 

Chad Pecot, MD, assistant professor, Department of Medicine, University of North Carolina (UNC) Lineberger Comprehensive Cancer Center, discusses the frontline standard of care in advanced squamous non—small cell lung cancer (NSCLC).

In the phase III KEYNOTE-407 trial, there was a significant improvement in overall survival (OS) with pembrolizumab (Keytruda) plus carboplatin and paclitaxel or nab-paclitaxel (Abraxane) versus chemotherapy alone. Notably, the trial allowed crossover, so when patients who didn't initially receive the immunotherapy started experiencing tumor growth, they were able to start receiving immunotherapy, explains Pecot. Even with the crossover, there was an improvement in OS was observed if the immunotherapy was received earlier on in treatment. Therefore, the earlier the immunotherapy was started, the better the survival benefit.

Additional analysis showed a benefit with the combination irrespective PD-L1 expression. Even patients who had no PD-L1 expression in their tumor had a notable OS benefit by adding immunotherapy. Furthermore, the regimen was observed to be well tolerated.

Chad Pecot, MD, assistant professor, Department of Medicine, University of North Carolina (UNC) Lineberger Comprehensive Cancer Center, discusses the frontline standard of care in advanced squamous non–small cell lung cancer (NSCLC).

Dr. Pecot on the Frontline Standard of Care in Squamous NSCLC

Chad Pecot, MD, assistant professor, School of Medicine, UNC Lineberger Comprehensive Cancer Center, discusses talimogene laherparepvec (T-VEC; Imlygic) in the treatment of patients with lung cancer.

T-VEC is genetically engineered from herpes to replicate preferentially inside cancer cells without giving the pathogenic disease. Pecot says that the idea is that it will lyce cancer cells once it replicates inside of them. It also produces a protein called GM-CSF, and what that will do is recruit a lot of immune cells to the tumor.

In lycing the tumor, T-VEC presents antigens from the tumor to the immune system, and secretes the protein GM-CSF in combination with immunotherapy. T-VEC plus immunotherapy has shown impressive response rates in melanoma, making the potential for the combination in lung cancer grow.

Dr. Pecot Discusses T-VEC in Lung Cancer

Chad Pecot, MD, assistant professor, School of Medicine, UNC Lineberger Comprehensive Cancer Center, discusses promising combinations for patients with non—small cell lung cancer (NSCLC).

IDO inhibitors plus nivolumab (Opdivo) and pembrolizumab (Keytruda) are viable combinations for patients with NSCLC. Both of these combinations were presented at the 2017 ASCO Annual Meeting. Response rates ranged from 40% to 50%. These were higher than historical rates without any added toxicities. This increases the likelihood of more combinations that could potentially increase response rates further, says Pecot.

A large phase I trial has been expanded to look at the combination of ipilimumab plus nivolumab. Bristol-Myers Squibb publicly announced that the trial was a success, but physicians are waiting on the most recent data. It seems that decreasing the dose of ipilimumab and spreading out how often it is given improves response compared with single-agent therapy, Pecot says.

Chad Pecot, MD, assistant professor, School of Medicine, UNC Lineberger Comprehensive Cancer Center, discusses promising combinations for patients with non–small cell lung cancer (NSCLC).

Chad Pecot, MD

Articles

Dr. Pecot on Selecting Between Available Targeted Therapies in NSCLC

Dr. Pecot on Addressing Mechanisms of Resistance With New Targeted Therapies in NSCLC

Dr. Pecot on the Growth of Actionable Targets in Lung Cancer

Dr. Pecot on the Frontline Standard of Care in Squamous NSCLC

Dr. Pecot Discusses T-VEC in Lung Cancer

Dr. Pecot on Immunotherapy Combinations in NSCLC