Andreas N. Saltos, MD

Andreas Saltos, MD, medical oncologist and clinical research medical director in the department of thoracic oncology at Moffitt Cancer Center, discusses the current space for patients with non-small cell lung cancer (NSCLC) harbording 

According to Saltos, since the start of a phase 1/1B trial (NCT01859026) which was created to examine the efficacy and safety of the combination of erlotinib (Tarceva) and binimetinib (Mektovi) for patients with 

-mutated NSCLC, a lot has changed. One of these developments includes a new approved inhibitor, osimertinib (Tagrisso).

Investigators continue to evaluate new combinations and trials for patients with NSCLC that harbor 

 Things have changed a lot since this study started. [Since this] study launched, things have changed a bit. We now have multiple approved EGFR inhibitors, including, most recently, a third generation of osimertinib [Tagrisso] which is more selective for the 

, and is currently our standard of care for those patients.

 space, especially about a year ago, things have changed dramatically with the approval of the first G12C specific KRAS inhibitor. Really, the novel mechanism of shooting 

 through these binding pockets and specific mutants really transformed our ability to target 

 in a way that we didn't have 5 or 7 years ago.

Videos

Andreas Saltos, MD, discusses the current space for patients with non-small cell lung cancer harbording EGFR and KRAS mutations.

Practice Changing Updates in the EGFR+ and KRAS+ NSCLC Space

Andreas Saltos, MD, medical oncologist and clinical research medical director in the department of thoracic oncology at Moffitt Cancer Center, discusses the key discoveries from a phase 1/1B trial (NCT01859026) of erlotinib (Tarceva) and binimetinib (Mektovi) in 

-mutated non–small cell lung cancer (NSCLC).

According to Saltos, there was limited efficacy in this patient population who was administered this combination, likely due to them not being able to achieve highly therapeutic doses of both drugs through tolerability.

However, there were signals in 1-2 patients with NSCLC harboring 

 mutations who had some degree of durable benefit from the combination.

One of the things that we noted in the presentation is that there were not necessarily many signals of increased efficacy in the combination in patients with 

 mutations more so than you may expect. This could be reflective of the lower doses that we had with a combination.

 I think it still remains to be seen whether strategies like this in 

 may be valuable. We already are seeing a lot of clinical trials underway, combinations with the new standard of care, third generation EGFR tyrosine kinase inhibitors. Before coming to conclusions about the effectiveness of combination strategies, I'd like to see data from those as well.

Andreas Saltos, MD, discusses the key discoveries from a phase 1/1B trial of erlotinib and binimetinib in EGFR- and KRAS-mutated non–small cell lung cancer.


Key Takeaways From a Trial of Erlotinib/Binimetinib in EGFR+ or KRAS+ NSCLC

Andreas Saltos, MD, medical oncologist and clinical research medical director in the department of thoracic oncology at Moffitt Cancer Center, discusses what he anticipates future research will examine regarding treatment options for 

-mutated non-small cell lung cancer (NSCLC).

Approximately 40%-50% of patients with NSCLC harbor 

 mutations. Due to his alarmingly high number, Saltos notes the importance of a phase 1/1B trial (NCT01859026) which was created to examine the efficacy and safety of the combination of erlotinib (Tarceva) and binimetinib (Mektovi) for patients with 

Investigators continue to evaluate new combinations and develop clinical trials for this patient population to combat this disease and target 

 I'm excited about the fact that this is a new territory for patients with these KRAS mutations, especially where the field has exploded. There's a lot of new combinations and a lot of new trials for these patients. With any luck, a few of these combinations will start to show a lot of promise preclinically.

 There's even more exciting work being done to combat the problems of early development of resistance, where I think some time on the horizon, there will be a day where patients with KRAS mutations and EGFR mutations will really be able to have quality targeted therapy that can control the disease for a long time.

Andreas Saltos, MD, discusses what he anticipates future research will examine regarding treatment options for EGFR and KRAS-mutated non-small cell lung cancer.

Looking Forward in EGFR+ and KRAS+ NSCLC

Andreas Saltos, MD, medical oncologist and clinical research medical director in the department of thoracic oncology at Moffitt Cancer Center, discusses the key takeaways for community oncologists in regard to his presentation on the phase 1/1b clinical trial exploring the use of binimetinib (Mektovi) plus erlotinib (Tarceva) in patients with non–small cell lung cancer (NSCLC) harboring either 

 mutations given at the 2022 American Association for Cancer Research (AACR) Annual Meeting.

the combination of binimetinib and erlotinib

 did not demonstrate signals of increased efficacy in patients with 

 mutations. Further studies are needed to see if strategies like this may be valuable in patients with these mutations.

Though little efficacy was noted in the populations administered this combination, Saltos remains hopeful and notes that the field of NSCLC with 

 mutation is growing. There are emerging targeted drugs currently under examination, all of which can potentially provide patients with targeted care in the future.

From this presentation, you can start to see that although there was limited efficacy in our populations with this combination, likely because we weren't able to achieve very highly therapeutic doses of both drugs through tolerability, we did see signals including in 1 or 2 patients with 

mutations who had some degree of durable benefit from the combination.

I think with the up and coming, newer, more targeted, tailored drugs like the targeted G12C inhibitors, we may start to see some headway that these patients may be candidates for targeted therapy, where typically we would think that targeted therapy is not an option. We've already seen that in the 

We're also seeing preliminary data, some that was also shared at AACR. Recently, the KRAS G12C specific inhibitor, sotorasib [Lumakras] has been explored in some combinations where we see even more promising signals of efficacy with EGFR and MEK combinations. Again, tolerability toxicity remains an issue. I think with emerging, tailored targeted drugs, that the field will bring us to a point where we'll be able to offer targeted therapy to more patients. Keep in mind that these patients have specific mutations, be on the lookout for clinical trial opportunities, and hopefully new drug approvals in the coming years for these patients.

Andreas Saltos, MD, discusses the key takeaways of the phase 1/1b clinical trial exploring the use of binimetinib plus erlotinib in patients with non–small cell lung cancer harboring either KRAS or EGFR mutations.

Reviewing Erlotinib/Binimetinib Combo in EGFR+ or KRAS+ NSCLC

Andreas Saltos, MD, medical oncologist and clinical research medical director in the department of thoracic oncology at Moffitt Cancer Center, discusses a phase 1 trial (NCT01859026) of binimetinib (Mektovi) and erlotinib (Tarceva) for patients with non–small cell lung cancer (NSCLC) and 

The study investigators were looking at whether the combination of binimetinib and erlotinib showed safety and efficacy for patients with NSCLC. Erlotinib is an 

 inhibitor used as targeted therapy for NSCLC, while the 

 inhibitor binimetinib is not currently approved for NSCLC. Saltos says that investigators theorized that dual inhibition of the MAP kinase pathway would have efficacy in patients with 

 mutations, which have limited targeted therapies available.

Of a total of 43 patients enrolled in the phase 1 or 1b parts of the trial, 17 (40%) had an 

 mutation. According to Saltos, investigators performed dose escalation of both drugs until they determined a recommended phase 2 dose. The safe dose was lower than the dosage each drug was approved for individually: 100 mg of erlotinib daily and 15 mg of binimetinib twice daily for 5 days a week. The toxicity was manageable, and investigators did not observe any significant drug interactions.

 Our group here at Moffitt Cancer Center conducted this phase 1/1b clinical trial exploring the use of binimetinib, which is a 

 inhibitor, in patients with NSCLC harboring either 

The rationale for the study came from the observation that a patients with 

-mutant lung cancer inevitably develop resistance to EGFR inhibitors, and patients with 

 mutations make up a large population of patients with this driver, 

, which until recently was undruggable. And with the theory that with dual inhibition in the MAP kinase pathway, where there's activation in both populations, we might be able to achieve better tumor control or better responses.

 In this phase 1 trial, we first were able to ramp up from a low doses of both drugs. And in our case, actually, we had to tune the doses down until we found ultimately a slightly lower dose than what's the approved use for both drugs was needed to manage the [adverse event] profile. Ultimately, we found that the dose of erlotinib, 100 mg daily with binimetinib, 15 mg twice a day, for 5 days a week, was our maximum tolerated dose or recommended phase 2 dose.

Andreas Saltos, MD, discusses a phase 1 trial of binimetinib and erlotinib for patients with non–small cell lung cancer and EGFR or KRAS mutations. 

Andreas N. Saltos, MD | Authors

Articles

Practice Changing Updates in the EGFR+ and KRAS+ NSCLC Space

Key Takeaways From a Trial of Erlotinib/Binimetinib in EGFR+ or KRAS+ NSCLC

Looking Forward in EGFR+ and KRAS+ NSCLC

Reviewing Erlotinib/Binimetinib Combo in EGFR+ or KRAS+ NSCLC

Binimetinib/Erlotinib Shows Tolerability in EGFR- or KRAS-Mutated NSCLC