For Patients with the Most Advanced Lung Cancers: “Nunquam Cede” (Latin-Never Yield)

I’ve long held that there are no bad cancers, just cancers that we can or cannot treat.

On September 14th, 2024, when a colleague asked me to see a 67-year-old woman with what appeared to be extensive metastatic cancer, I had to question that premise. With a 50-year history of cigarette smoking, this pale, ill-appearing, emaciated woman presented with innumerable lung, bone, and subcutaneous masses scattered throughout her body.

While I presumed this was lung cancer, the first biopsy was non-diagnostic. More troubling, every single tumor maker was markedly elevated. From CEA (colon) to CA19.9 (pancreas), to CA 15.3 and CA 27.29 (breast), to CA 125 (ovarian), this cancer was on a tumor marker tear. A second surgical biopsy was needed to make a diagnosis.

Tissue submitted to our laboratory identified several chemotherapies and two particularly active new drugs. The first is an experimental agent that targets the K-RAS oncogene and is proceeding through clinical trials. K-RAS is the most common gain-of-function cancer mutation, and these results strongly suggested that K-RAS was active in this patient’s tumor. But K-RAS is common in colon (40%), pancreatic (85%), and lung cancers (30%), leaving us no clear pathway forward.

The second finding, however, was a tiebreaker. This drug selectively targets only one specific form of the K-RAS mutation known as the G12C subtype. While 40% of lung cancers with KRAS are G12C subtype, only a very small percentage of colon and pancreatic cancers carry G12C. The “smoking gun” (pun intended) was lung cancer.

Here just 5 days after her surgery, our EVA/PCD results not only told us the type of cancer she had, but also told us exactly how to treat it. More to the point, our EVA/PCD technology has been shown to provide a twofold higher response rate for selected patients.

Based on our findings, her response would now be 2 x 43%, or 86%. In widely metastatic lung cancer, 86% is quite close to a home run.

It was then that the saga took a turn.

First, current FDA criteria only allow the use of this drug after patients have received prior chemotherapy. That is, we could not give this treatment in the first-line setting.

Second, reimbursement policies make it impossible to obtain this life-saving drug for patients while they remain in the hospital. It’s simply not available for inpatients.

Third, the use of this drug is dependent upon a positive gene test for G12C, a process that takes weeks to complete.

Things went from bad to worse. The patient fractured her shoulder and left hip by simply climbing out of bed. The disease was on fire, and I became concerned that she would die before I could even try to treat her.

Following surgical fixation of the hip and arm, we dutifully administered the required chemotherapy as the patient underwent physical therapy. I explained to her husband repeatedly that I knew that she would respond if I could just get the right treatment started.

Weeks later, the gene analysis returned. As predicted, she carried the K-RAS G12C mutation. With our foreknowledge, we were already well on our way to obtaining the drug.

Several days ago, I received a phone call from her physician. After barely 3 weeks on oral therapy, he could not contain his excitement.

He was stunned by the degree of response. Virtually all the patient's disease had resolved. Where there had been lumps under the skin, there was only mild irritation.

Where the patient had required narcotics, she was off pain meds. Where she had required assistance with every movement, she was now weight bearing and beginning to walk.

The response was nothing short of miraculous.

There are several very important lessons learned.

First: These new classes of agents offer real hope for previously untreatable cancers. Though these drugs are not curative, that response rate is a blessing in and of itself.

Second: Our regulatory and reimbursement policies are not keeping pace with advances in cancer therapeutics. That is something that must be addressed at a policy level.

Third: Byzantine insurance rules make it increasingly difficult for cancer doctors to do their jobs.

Fourth: Even the most sophisticated genetic (DNA) profiles can’t identify clinical responders.

Here, a 42.9% expectation of response from the published data in G12C (Janne, P. et al NEJM 2022) can’t hold a candle to the more biologically relevant tissue-based predictions of EVA/PCD, not in turn-around time (days versus weeks) nor predictive accuracy; improving a 43% to 86% expectation of response.

Fifth: Regulatory agencies’ unwavering reliance on gene tests above all other platforms (EVA/PCD among them) is denying patients life-saving technological advances.

Finally: There are no bad cancers, just cancers that we can or cannot treat.

Every patient deserves the right to the best possible outcome. This is but one example of the right drug for the right patient at the right time.