(2019 ASCO) June 1, 2019 – Five-year data from the phase Ib KEYNOTE-001 clinical trial show that pembrolizumab (Keytruda) was safe and effective and substantially increased overall survival for advanced non-small cell lung cancer (aNSCLC). Specifically, 23.2% of people who had not previously been treated with chemotherapy and 15.5% of previously-treated patients were alive after five years, with the greatest benefit observed in patients with higher PD-L1 expression. This represents a marked improvement over 5-year survival rates from the pre-immunotherapy era, which averaged 5.5% for aNSCLC. This is the longest follow-up study to date of people with aNSCLC treated with pembrolizumab, according to the researchers.

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H. Jack West, MD (Posted: June 05, 2019)

While in keeping with what we see informally in our clinics, these documented results from primarily previously treated patients a trial setting highlight the amazing advance that PD1/PD-L1 directed immunotherapy represents in NSCLC. We are seeing a significant minority of our patients alive 5 years out from starting a salvage therapy, and even 25% of patients with high tumor PD-L1 (50% or higher); many are without evidence of active disease. It is truly remarkable, though the fact that there are clear differences based on PD-L1 expression highlight that there are still some patients who are much more or less likely to be major beneficiaries.

(Merck) Apr 11, 2019 - KEYTRUDA now approved for first-line treatment of patients with stage III NSCLC who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors express PD-L1 (TPS ≥1%), with No EGFR or ALK genomic tumor aberrations. Merck, known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved an expanded label for KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the first-line treatment of patients with stage III non-small cell lung cancer (NSCLC) who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors express PD-L1 (tumor proportion score [TPS] ≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

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H. Jack West, MD (Posted: April 12, 2019)

This new approval is more likely to lead to worse care rather than net benefit. The approval of pembrolizumab for patients with a lower threshold tumor PD-L1 of 1% is based on the KEYNOTE-042 trial being positive against chemo doublet alone in this broader population. However, pembrolizumab was already approved for patients with high PD-L1 of 50% of greater, and that group was the one that drove the positive results of the trial overall, essentially "carrying" the group with tumor PD-L1 1-49%, who did no better with pembro monotherapy than with doublet chemotherapy. The trial was positive despite having favorable results with pembro from the high PD-L1 group diluted by the extremely weak results with pembro monotherapy for the low PD-L1 group. Some will say that the fact that the first line pembrolizumab arm did just as well in overall survival as doublet chemo means that this now makes pembrolizumab a viable alternative. That might be the case except that the chemo alone arm was not permitted to cross over to immunotherapy upon progression, which has been a well established standard of care for years in patients with advanced NSCLC and who progressed after first line chemotherapy. The first line pembro arm only did as well as a hobbled, substandard of care arm that started with chemo and couldn't get subsequent immunotherapy. On the other hand, every patient who started on pembro could easily transition to chemo later. Finally, the inclusion of patients with stage III NSCLC who are not able to get chemo/radiation is another concern, since the current standard of care in this setting, chemoradiation followed by durvalumab, is a potentially curative therapy. These were not patients who were the planned subjects of KEYNOTE-042. For patients with stage III NSCLC to receive single agent pembrolizumab rather than chemoradiation would be an egregious affront to our best data-driven standards.

(ELCC 2019) Apr 11, 2019 - Maintenance immunotherapy fails to improve survival in extensive-stage small cell lung cancer (SCLC), according to late-breaking results from the CheckMate 451 study to be presented today at the European Lung Cancer Congress 2019. Around 60–70% of patients with SCLC have extensive disease at the time of diagnosis, meaning it has spread beyond a single lung and nearby lymph nodes and cannot be treated with radiotherapy.

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H. Jack West, MD (Posted: April 11, 2019)

A disappointing failure, but one that at least leaves the new standard of first line carbo/etoposide/atezolizumab, which showed a survival benefit over chemo alone in the IMpower133 trial, as an uncontested leading approach today. Surprising to see such weak results even for the nivolumab/ipilumumab doublet, but the fact that there's a suggested benefit on the far right end of the curve highlights that there is a subgroup who do well with immunotherapy -- we just need to figure out how to identify them prospectively.