Chemotherapy After Progression of PD-L1+ Squamous NSCLC

Corey Langer, MD:So, in individuals whose disease has progressed on checkpoint blockade, who do not have an actionable oncogenic driver, the standard approach is chemotherapy. And the same principles apply to that individual as would apply if they were treated up front, were chemotherapy-naïve, and receive chemotherapy as our first-line approach. This individual is still fit. The seizure presumably has been treated with anticonvulsant therapy. He’s receiving whole grain radiation. Assuming performance status is not deteriorating, I would still favor a 2-drug combination with platinum and some partner agent. And the standard agents in this setting include taxanes and gemcitabine along with carboplatin. Some may prefer a solvent-based paclitaxel, others may prefer docetaxel. My go-to agent, particularly in the elderly with squamous cell, is nanoparticle albumin-bound paclitaxel given weekly with carboplatin.

In my experience, at least over the last 3 to 4 years where I routinely started adopting nanoparticle albumin-bound paclitaxel, since about 2013, I’ve been pleased with both the efficacy and toxicity profile. By and large, this drug is a bit easier to give than solvent-based paclitaxel; it takes half an hour tops. It does not require premedication. Incidence of neuropathy is generally a bit lower. And when the drug is stopped, neuropathy will mitigate, sometimes reverse, a lot more quickly than we see with standard solvent-based paclitaxel. With a weekly regimen, by and large, I see a bit less myelosuppression compared to our conventional Q3-week approach.

In terms of response rates, the literature, at least in squamous cell, documents about a 40% to 44% response rate. And my own personal experience pretty much matches the numbers seen in the phase III trial. The median progression-free survival, by and large, is a minimum of 6 months. There is now an ongoing randomized phase III trial, squamous-specific, that is looking at 4 cycles, 12 weeks of nab-paclitaxel with carboplatin, and then a randomization: either maintenance nab-paclitaxel alone, single-agent, or observation. That trial is continuing to accrue. And in the context of the elderly, we have looked at, in the ABOUND.70 program, 2 different schedules of nab-paclitaxel and carboplatin. One is the conventional weekly uninterrupted approach and the other is the 3-week-out-of-4 schedule, very similar to a prior paclitaxel/carboplatin schedule that was investigated in France. So, the big question is, can we give this agent more safely in the elderly using a 3-week-on-1-week-off approach, help mitigate toxicity and yet preserve response rate and progression-free and overall survival? And those data are just being assessed.

Individuals with advanced lung cancer really need to be addressed holistically. It’s not just a matter of using chemotherapy to attack the cancer. We have to look at the entire patient. There’s a very important paper by Jennifer Temel, published in theNew England Journal of Medicinearound 2011, that looked at proactive, preemptive supportive care versus our more usual reactive symptom-generated approach. These were individuals all with advanced disease who, at the time of diagnosis, were randomized to a monthly meeting with the supportive care, palliative care team, include pain management and specialists, nutritionists, social work, and various approaches toward anxiety and depression. And the control group got standard treatment of chemotherapy. If they happened to have a complaint, they would then be referred to the appropriate specialist, but they weren’t seen in a proactive preemptive manner.

The group that received the preemptive integrated approach did far better. They had much less anxiety, much lower rates of depression. They were much less likely to be hospitalized toward the end of their lives. They had lower hospitalization rates, much more appropriate hospice use. And then, the icing on the case, they lived longer. Their median survival was more than 2 months greater than the reactive group. The problem is, it’s not a drug, so there’s no reimbursement for this approach or inadequate reimbursement. And needless to say, if any systemic agent had generated similar survival benefits, we’d be talking about a multimillion dollar blockbuster. So, this form of preemptive action of simple involvement, holistic approach toward the patient—not just the elderly patient, but any patient with advanced disease—I think is highly warranted, and we have phase III data that justify its proactive use.

Transcript edited for clarity.

November 2016

• An 81-year-old male presents to his physician with symptoms of cough, hemoptysis, and fatigue requiring frequent rest during the day
• PMH includes hypercholesterolemia, controlled on simvastatin and hypertension, controlled on a calcium channel blocker; mild osteoarthritis
• He has no history of smoking
• The patient is physically active and plays golf several days per week
• CT of the chest revealed a solid cystic mass in the left upper lobe and lymphadenopathy in the left hilar and bilateral mediastinal nodes
• PET/CT imaging showed 18F-FDG uptake in the lung mass, left hilar and both mediastinal lymph nodes
• Bronchoscopy and transbronchial lung biopsy were performed
• Pathology showed grade 3 squamous cell carcinoma of the lung
• Genetic testing was negative for known driver mutations
• PD-L1 testing by IHC showed expression in 65% of cells
• The patient was started on therapy with pembrolizumab
• Follow up imaging at 3 months showed stable disease

April 2017

• After 5 months on immunotherapy, the patient was hospitalized after having a seizure. He reported worsening fatigue and cough for 1 month
• CT showed increased size of the left upper lobe pulmonary mass
• Brain imaging showed several small intracranial lesions
• WBRT was started
• Immunotherapy was discontinued and the patient was started on carboplatin and nab-paclitaxel