Sandip Patel, MD, discusses the durability of immunotherapy responses, updated survival data from clinical trials, and considerations for patients in the metastatic lung cancer setting.
62-year-old woman presented to the ED with vague complaints of voice changes and cough.
Past Medical, Family, and Social History
Final Pathology: consistent with squamous cell carcinoma; metastatic stage IV
PD-L1 expression by IHC: 0%
NGS: No actionable mutations
Sandip P. Patel, MD: There are multiple chemoimmunotherapy and immunotherapy doublet clinical trials that have had updates in their survival data over the past year. Many of these are multi-year updates showing continued benefit for patients who received immunotherapy. Their last dose of immunotherapy may have been 2, 3, or even more years ago, showing the durability for immunotherapeutic response. One regimen for which we had an update for is the CheckMate-9LA study [NCT03215706], for which we had a 4-year clinical update. This is 2 cycles of chemotherapy with nivolumab plus ipilimumab, 1 mg/ kg every 6 weeks, and a CTLA-4–blocking drug. Here we see a 4-year survival update, which recapitulates what we saw with the CheckMate 227 [NCT02477826] results: that there’s a subgroup of patients who have continued responses years after their last dose of treatment. In my clinic, I consider this type of regimen for patients who are PD-L1 negative, have squamous histology, have brain metastases, or have STK11/KEAP1 biology.
Now, when we add additional anticancer agents, there’s always the risk of not only having increased antitumor responses, but also on the flip side, the double-edged sword of unfortunately immune-related adverse events. With the introduction of anti–CTLA-4 blockade, in particular, endocrinopathies and colitis tend to be the adverse effects that increase. The pneumonitis tends not to increase with the introduction of anti–CTLA-4. It’s important that we educate the patients and their caregivers on these toxicities because otherwise, this can be a very safe regimen given that…dosing here is a lower dose than what’s given in melanoma and renal cell carcinoma. The toxicity profile here is much more tolerable for patients, broadly speaking, than compared with what we give in kidney cancer or melanoma.
An additional update we had was the KEYNOTE-407 [NCT02142738], which is chemotherapy, carboplatin/paclitaxel, plus pembrolizumab in squamous histology, for which we had an update showing benefit, mainly driven by patients with greater than 1% PD-L1 expression, particularly greater than 50% PD-L1 expression with squamous histology. Another study with a recent update is cemiplimab plus chemotherapy in both squamous and nonsquamous non–small cell lung cancers. The EMPOWER-Lung 3 study [NCT03088540], which as similar to the other studies mentioned, shows a continued benefit for those patients with potential enhanced activity in patients with squamous histology. Though this is a retrospective look at the data of that subgroup.
Finally, another CTLA-4–containing regimen with chemotherapy and an anti–PD-L1 is the POSEIDON [NCT03164616] regimen, which includes chemotherapy and tremelimumab for 5 cycles followed by durvalumab. This is a frontline study similar to the other studies. We saw updated data that show hints of benefit in particular patient populations, including those patients with STK11/KEAP1 mutations. In totality, these are studies that show the continued benefit of a particular chemoimmunotherapeutic approach for those patients who lack EGFR and ALK mutations in the frontline metastatic space. Thinking about when to introduce CTLA-4, it remains a question for which we lack prospective data on but have multiple retrospective studies in subgroups that may inform patient populations that can potentially benefit.
Transcript is AI-generated and edited for readability.