How to Handle Elderly Patients and Those With Performance Status 2 NSCLC

At the Great Debates & Updates in Lung Cancer meeting in New York, New York, Corey Langer, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, discussed the therapeutic landscape for underserved patients with non-small cell lung cancer — elderly patients, and patients with ECOG performance status 2.

Transcript:

Hi, I'm Corey Langer, I'm the Director of Thoracic Oncology at the Abramson Cancer Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, and it's been my honor to co-chair this meeting.

As I've often done in the past, I had the privilege of reviewing the therapeutic landscape in what I consider to be underserved populations, those with compromised performance status, what we call PS2 and then the elderly. And although they're underserved, they actually in aggregate constitute the majority of patients we see. PS2 individuals are probably about 30% to 40%, and the median age of lung cancer is 70. Yet unfortunately, when you look at clinical trials, those who are 70 years of age and older really constitute probably less than 15% to 20% of all trial enrollments. The clinical trials from which we derive basically our therapeutic understanding of the disease are skewed very much to our much more high-functioning patients and much younger patients and it remains to be seen how emblematic those trials are of the general lung cancer population.

I focused on studies that were specific to PS2 individuals and the elderly and also looked at secondary analyses of much broader trials that included both groups. At least for the elderly, I think we've learned that the fit elderly do as well or nearly as well as fit younger patients, that as long as they don't have a super abundance of comorbidities, outcomes will be very similar. There have been elderly-specific trials that have verified the primacy of platinum-based treatment showing that platinum combinations are superior to single agents right up to the age of 90 and including PS2 individuals. TKIs, tyrosine kinase inhibitors, there's no impediment to their use in the elderly, the oncogenic driver really trumps both age and performance status and frankly, performance status trumps age when it comes to older individuals.

Immunotherapy poses a challenge in each of the phase 3 trials that have led to approvals of checkpoint inhibitors either alone or in combination with chemo. Number one, the elderly were underrepresented. Number two, outcomes were never quite as good in the elderly population as they were in younger individuals. The hazard ratios, the relative percent to improvement in outcome, tended to be smaller so if a study had an overall hazard ratio of 0.6, and maybe 0.5 for those under 65 years of age, the hazard ratio might've been 0.8 or 0.85 for the older group. Again, a trend toward benefit, but the confidence intervals often overlapped in unity. In some cases, no obvious benefit at all for individuals over the age of 70 or 75 so I think we have to be careful about immediately extrapolating positive results to all the individuals we see.

Performance status, basically the same issue, although here oncogenic drivers again, are paramount. If an individual is ill, they're hospitalized, they may even be in the ICU, if they've got an oncogenic driver and they get the appropriate intervention, the appropriate tyrosine kinase inhibitor in general, they can do extraordinarily well. I've called it the Lazarus Phenomena where patients literally seem to be arising from their death beds, and I have witnessed that and it's incredibly gratifying when that occurs, but you have to look to find it. These oncogenic drivers do not declare themselves on their own.

And when it comes to checkpoint inhibitors, a similar phenomenon seems to be occurring on those who have high levels of PD-L1, 50% or more, which is about a third of our wild-type non-small cell patients they too can do extraordinarily well.

Neither age nor performance status should be an impediment to appropriate treatment but in the elderly and those with compromised performance status, we have to recognize their vulnerability and at least be prepared to adjust our treatments, make some allowances for the compromises that exist.

Source:

Langer C. Novel checkpoint inhibitor combinations for lung cancer. Presented at Great Debates & Updates in Lung Cancer; September 21-23; New York, NY.