Selecting a Frontline Regimen for Non-Driver NSCLC

Mark Socinski, MD:In patients with a good performance status with recently diagnosed stage 4 squamous carcinoma, the standard of care is a platinum-based doublet. Now, the choice of platinum that we have is really either cisplatin or carboplatin. I tend to use carboplatin; it’s a little easier, with a more favorable toxicity profile. And then you pair that with a second drug. Now, that second drug typically is one of the taxanes, and we have 3 choices. Paclitaxel or nab-paclitaxel as well as docetaxel are all reasonable, or gemcitabine. In this case, our patient was treated with gemcitabine, which is an option in this setting. In my practice, I tend to use nab-paclitaxel in combination with carboplatin because of the higher response rates seen in that. And the justification for that is that almost all patients with stage 4 disease with squamous have some symptom burden. And since the higher response rate is there, it’s more likely to have a palliative effect at symptom relief. And there is actually evidence in the literature to support that.

The worsening fatigue typically occurs after 3 or 4 cycles or so. Fatigue can be present at the time of diagnosis. Fatigue is obviously a very nonspecific symptom. Sometimes it can be related to anemia, sometimes it can be related to the disease or the treatment, and sometimes it can be an early sign of depression and other things ongoing. So, I think you have to kind of cast a wide net in terms of thinking about fatigue in these patients in trying to address it, because in many studies that tends to be the most common toxicity we see in these patients. But it’s also a very complicated toxicity.

What we’ve addressed so far is the treatment of good performance status patients. And those would be an ECOG performance status of 0 to 1. When you get a little bit more compromised either by your disease or by your comorbidities and you get to PS of 2, for the most part, I still use platinum-based doublets if I think the cancer is driving the performance status. Sometimes, there are patients who have such extensive comorbidities that I may not use a platinum-based doublet. I may use single-agent therapy in that setting.

If the performance status erodes to a performance status of 3 or 4—unless you have an oncogenic driver, which is exceptionally rare in these patients—then the standard of care is best supportive care in that population, and I would consider hospice care in the very poor ECOG performance status 3 or 4 patient.

Transcript edited for clarity.

• A 72-year old male presented with dyspnea, weight loss, chronic cough, fatigue, and back pain
• PMH: current non-smoker for the past 10 years with 40-year (1-pack/day) smoking history, COPD, controlled on LABA/LAMA/ICS; hyperlipidemia controlled on atorvastatin
• Chest CT scan showed a 3.5-cm nodule in the upper lobe of the left lung
• MRI of the brain revealed lesions in the left cerebellum and left frontal lobe
• 99mTc bone scan showed increased uptake in the L1 vertebra and eighth rib
• ECOG PS=1
• Pathologic diagnosis of biopsy under bronchoscopy was squamous cell carcinoma
• IHC: PD-L1 expression in 0% of cells
• Patient was started on gemcitabine/cisplatin
• Brain metastases treated with stereotactic radiotherapy
• At 6 months, patient reported worsening fatigue
• Follow up MRI scan showed no evidence of new brain metastases
• CT scan showed new lesions in the right lung and liver
• Patient was started on atezolizumab; ICS medication for COPD was discontinued
• Patient reported decreased appetite, which resolved following implementation of self-management techniques