Has treatment for cancer improved and how much?

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www.sarah-constantin.org/blog/2018/1/14/chemothera...

I am not impressed with that summary for a variety of reasons, including outright errors.

Here is a paragraph re traztuzumab (HERCEPTIN):

"Trastuzumab

This is an HER2 inhibitor for advanced breast cancer. In combination with docetaxel, vs. docetaxel alone, it had a median overall survival of 31.2 vs 22.7 months, and a 61% overall response rate vs. 34%. Another study comparing trastuzumab adjuvant chemotherapy vs. chemo alone found 3-year overall survival was not significantly different between the three groups, but progression-free survival was (71% vs. 56%). The HERA trial, the largest of these so far with 3401 patients in total, found no significant difference in overall 4-year survival, and a statistically significant but small difference in disease-free 4-year survival (78.6% vs. 72.2%.) A five-year study found that overall survival with trastuzumab was comparable to HER2-negative patients (5-year survival of about 30%, 1-year survival of 75% and 86%) and higher than HER2-positive patients without trastuzumab (5-year survival rates of about 20%, 1-year survival of 70%). A study of 4045 women with HER2 positive, non-metastatic breast cancer found a 4-year survival rate with trastuzumab of 93.0% vs. 85.6% without."

"This is an HER2 inhibitor for advanced breast cancer."

This is wrong. Trastuzumab gained approval by FDA for early stage breast cancer years ago.

The blog post linked above is neither comprehensive nor current regarding breast cancer drugs.

The sum total of the information on palbociclib in the blog post is the sentence quoted by marijen:

"Palbociclib is a CDK4 and CDK6 inhibitor for ER-positive and HER2-negative advanced breast cancer. It increases progression-free survival from 10 months to 20 months but does not increase overall survival times (37.5 months with palbociclib + letrozole vs. 33.3 months with letrozole alone.)"

The second citation is to an August 2014 review article that cites to a 2014 meeting abstract reporting results from "PALOMA-1/TRIO-18", a small Phase II trial performed in 165 patients, in which 84 were assigned to palbociclib plus letrozole and 81 to letrozole alone.

What the second citation actually says about overall survival is:

"An interim analysis of overall survival, based on 61 patients, showed a nonsignificant trend in favor of the combination (37.5 months versus 33.3 months, respectively; HR 0.813; P=0.2105), these data were immature, and final analysis is outstanding."

I find it interesting that the blogger failed to mention that this result was: (i) from a Phase II trial; (ii) based on only 61 patients; and (iii) was an interim analysis of overall survival, and that the assessment of overall survival was on-going at the time. Seems important.

These interim results from 61 patients simply do not support the blogger's statement that palbociclib "does not increase overall survival times." While a statistically significant improvement in overall survival was not demonstrated, such a result does NOT establish that the drug "does not increase overall survival times." It doesn't demonstrate an improvement, but it is not adequate to negate a possible overall survival benefit either.

As it happens, final overall survival from the Phase II PALOMA-1/TRIO-18 trial were published here are are not that different from the interim result:

Finn (2017), "Overall survival results from the randomized phase II study of palbociclib (P) in combination with letrozole (L) vs letrozole alone for frontline treatment of ER+/HER2– advanced breast cancer (PALOMA-1; TRIO-18)"

http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.1001

"As of Dec 2016, there were 116 OS events. Median OS was 37.5 mos (95% CI: 31.4, 47.8) with P+L vs 34.5 mos (95% CI: 27.4, 42.6) for L (HR = 0.897 [95% CI: 0.623, 1.294]; P= 0.281)."

"In PALOMA-1, P+L provided a statistically non-significant trend towards an improvement in OS. Survival data from the phase III, PALOMA-2 study is awaited."

That said, Phase II trials in the advanced breast cancer setting typically are not designed to and are not capable of detecting a statistically significant improvement in overall survival, usually because their size limits statistical power. As noted here, the Phase II PALOMA-1/TRIO-18 trial "was not powered to look at overall survival."

As of this date, some results of Phase III trials are now available for palbociclib, including PALOMA-2 (a Phase III trial of palbociclib plus letrozole) here and PALOMA-3 (a Phase III trial of palbociclib plus fulvestrant) here and here, the latter noting that overall survival follow‐up in PALOMA-3 is in progress.

This Feb. 2017 feature notes that:

"While we do not yet have data for overall survival from any of the phase III trials of CDK4/6 inhibitors, the doubling in progression-free survival seen with the addition of CDK4/6 inhibition to endocrine therapy represents a breakthrough in the treatment of patients with metastatic hormone receptor–positive breast cancer."

Other CDK inhibitors are being evaluated, including abemaciclib and ribociclib. Here's an editorial from the scientific literature with a more favorable take on the achievements with respect to this class of drugs:

Griggs (2017), http://ascopubs.org/doi/full/10.1200/JCO.2017.73.9375

BarredOwl