(Lilly) Oct 7, 2019 - CYRAMZA, in combination with erlotinib, significantly delayed disease progression in previously untreated patients with metastatic non-small cell lung cancer whose tumors have activating EGFR mutations. In the RELAY study, treatment with CYRAMZA in combination with erlotinib demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) – the time patients lived without their cancer growing or spreading after starting treatment – compared to erlotinib alone.

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H. Jack West, MD (Posted: October 07, 2019)

Though the progression-free survival (PFS) for this global trial is very encouraging, we've seen other work out of Japan on erlotinib + VEGF inhibitor (bevacizumab previously) demonstrate a highly significant improvement in PFS that didn't translate into an improvement in overall survival (OS). I would say that based on the Japanese research, plus with the added burden of regular IV infusions added to an otherwise oral regimen, and the lack of CNS activity compared to the competing standard of osimertinib, I don't think this combination regimen will gain much traction in the absence of further follow-up demonstrating a significant OS benefit.

(ESMO 2019) Sept 28, 2019 - New data have shown that first-line treatment with a combination of two immunotherapy drugs improves overall survival in a subset of patients with advanced non-small cell lung cancer (NSCLC) compared to chemotherapy (1). The data from the CheckMate-227 trial, reported at the ESMO Congress 2019, suggest that the combination of nivolumab plus low-dose ipilimumab could offer a chemotherapy-free option for first-line treatment of patients with advanced NSCLC. Nivolumab, a PD-1 antibody, and ipilimumab, an anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody, are immune checkpoint inhibitors with distinct but complementary mechanisms of action.

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H. Jack West, MD (Posted: October 01, 2019)

The impact of the CheckMate-227 trial remains to be seen. While it was positive for an overall survival benefit, this was observed in the patients with PD-L1 expression 50%, but not in the patients with PD-L1 expression in between. This pattern doesn't give us a lot of confidence. At the same time, the OS benefit was compared to chemo alone, while the current standard of care is now chemo/pembro in most of these patients (certainly those with PD-L1 <1%), in whom there was a significant survival benefit seen in the KEYNOTE-189 and KEYNOTE-407 trials for patients with advanced non-squamous and squamous NSCLC, respectively. I expect that the appeal of a non-chemotherapy regimen will have some appeal to patients and oncologists, but we should recognize that non-chemo doesn't mean non-toxic. I expect that nivo/ipi will be a minor player compared to our current standards, likely used in <10% of patients in front line advanced NSCLC.

(ESMO 2019) Sept 28, 2019 - First-line osimertinib significantly lengthens overall survival compared to older generation EGFR-TKIs in patients with Ex19del/L858R EGFR mutated advanced non–small cell lung cancer (NSCLC), according to late breaking results of the FLAURA trial presented at the ESMO Congress 2019 in Barcelona, Spain. (1) The primary endpoint of progression free survival (PFS) was previously reported. (2) Survival data are now mature: the median overall survival with osimertinib was 38.6 months versus 31.8 months with first generation EGFR-TKIs, with a hazard ratio of 0.799 (p=0.0462). More than half (54%) of patients in the osimertinib group were alive at three years compared to 44% in the standard care group.

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H. Jack West, MD (Posted: October 01, 2019)

An important result that should satisfy the holdouts who were waiting on a demonstrated improvement in overall survival while considering the potential utility of a sequential approach. The trial has a few flaws, most notably not requiring a baseline MRI and not requiring treatment of detected brain mets -- both factors that clearly benefit the osimertinib arm -- and the rate of subsequent therapies is conspicuously lower than expected. Nevertheless, the efficacy, tolerability, and CNS activity of osimertinib are all very favorable, and the biggest limitation in its global use is the aggressive pricing, which precludes its availability for many EGFR mutation-positive patients around the world and makes it a financial challenge for many of those who can access it.